Raquitismo hipofosfatémico familiar ligado al cromosoma X: Reporte de Caso

El Fósforo es regulado por el riñón y el sistema óseo orquestado principalmente por la acción de la parathormona (PTH) y una molécula recientemente descrita como el factor de crecimiento fibroblástico 23 (FGF-23) . Presentamos los casos de dos pacientes madre-hijo con Raquitismo hipofosfatémico ligado al cromosoma X. Se realizó el estudio genético identificándose una mutación en el Gen PHEX: variante patogénica tipo splicing en hemicigosis: mutación previamente descrita como HGMD CS126536. El Raquitismo Hipofosfatémico forma parte de un grupo de tubulopatías caracterizadas hiperfosfaturia. La mutación del gen PHEX con pérdida de función conduce al aumento de FGF-23. PHEX degrada el FGF-23 en fragmentos inactivos, evitando la excreción excesiva de fosfatos y el desarrollo de hipofosfatemia. En un paciente con hipofosfatemia no dependiente de la hormona PTH o de la vitamina D y de presentación familiar debe considerarse el diagnóstico de Raquitismo hipofosfatémico ligado al cromosoma X.

Phosphate is regulated by the kidneys and the osseus system, mainly due to the action of parathyroid hormone (PTH) and a recently described molecule, fibroblast growth factor 23 (FGF-23). We present the cases of two patients, mother and son with X-chromosome linked hypophosphatemic rickets. The genetic study was performed, and a mutation in the PHEX gene was identified, a splicing type pathogenic variant in hemizygosis. This mutation was previously described as HGMD CS126536. Hypophosphatemic rickets belongs to a group of tubulopathies characterized by hyperphosphaturia. PHEX gene mutation with function loss leads to increased FGF-23 levels. PHEX degrades FGF-23 into inactive fragments, preventing excessive phosphate excretion and the development of hypophosphatemia. In patients with PTH or vitamin D non- dependent hypophosphatemia, a diagnosis of X-chromosome linked hypophosphatemic rickets should be considered.

Enfermedad ósea metabólica del prematuro: revisión de tema / Metabolic bone disease of prematurity: topic review

Resumen La enfermedad ósea metabólica del prematuro es una patología multifactorial que representa una importante causa de morbilidad, cuya prevalencia ha aumentado. Su diagnóstico requiere criterios bioquímicos, radiológicos y, en etapas avanzadas, clínicos; por lo cual, muchos autores recomiendan estrategias de tamizaje y prevención. El objetivo del presente artículo es realizar una revisión de los aspectos más relevantes respecto a la enfermedad ósea metabólica del prematuro, con énfasis en la prevención y tratamiento precoz. Se realizó una revisión bibliográfica con términos MeSH, en las bases de datos de Pubmed, ClinicalKey, ScienceDirect, SciELO y LILACS. Aunque no hay consenso en las pautas de tamizaje, diagnóstico y tratamiento, la principal estrategia usada en la actualidad es el soporte nutricional individualizado que cubra las demandas de calcio, fósforo y vitamina D, asociado a métodos de intervención clínica y seguimiento de bebés de alto riesgo. La comprensión de esta patología permitirá mejorar las estrategias de tamización, diagnóstico precoz, y de esta forma evitará complicaciones.

Abstract Metabolic bone disease of prematurity is a multifactorial pathology that represents a significant cause of morbidity and has increased in prevalence. Its diagnosis requires biochemical, radiological, and, in advanced stages, clinical criteria; therefore, many authors recommend screening and prevention strategies. This article aims to review the most relevant aspects of the metabolic bone disease of prematurity, with emphasis on prevention and early treatment. A bibliographic review was carried out with MeSH terms in the Pubmed, ClinicalKey, ScienceDirect, SciELO, and LILACS databases. Although there is no consensus on screening, diagnosis and treatment guidelines, the main strategy currently used is to provide individualized nutritional support that covers the demands of calcium, phosphorus and vitamin D associated with clinical intervention methods and monitoring of high-risk babies. Understanding this pathology will improve screening strategies and early diagnosis and thus avoid complications.

Raquitismo hipofosfatémico ligado al cromosoma X: un reto diagnóstico y terapéutico

La hipofosfatemia ligada al X es un desorden genético ocasionado por mutaciones del gen PHEX (phosphate regulating endopeptidase analog, X-linked). Esta afecta la codificación de una metaloproteasa que tiene como función inhibir el factor de crecimiento fibroblástico - 23 (FGF-23), promoviendo la pérdida renal de fosfato. A continuación, describimos el caso de un paciente de edad pediátrica a quien se le hace diagnóstico en la adolescencia con una mutación del gen PHEX. Posteriormente, la misma alteración genética fue encontrada en la madre, considerada como una mutación espontánea que fue trasmitida a su hijo. Esto aumenta la rareza del caso, donde el reto para diagnosticar esta patología necesita vencer dificultades administrativas, económicas y sociales. El diagnóstico y tratamiento oportuno ayudan a optimizar la talla final y minimizar todas las deformidades esqueléticas presentadas, tanto en la madre como en el hijo. En la actualidad se cuenta con el tratamiento tradicional y uno novedoso que fue ordenado para el paciente pediátrico de este reporte.

SUMMARY X-linked hypophosphatemia is a genetic disorder caused by PHEX gene mutations, which affects the encoding of a metalloprotease whose function is to inhibit fibroblastic growth factor-23 (FGF-23), promoting phosphate renal loss. Following we describe the case of a teenager diagnosed with a PHEX gene mutation. The same genetic alteration was found in the mother of the patient, considering a spontaneous mutation that was transmitted to her son, which makes the case, even rarer, where the diagnostic challenge needs to overcome administrative, economic and social difficulties. A timely diagnosis and treatment could help optimize the final height and minimize the skeletal deformities presented in both the mother and the child. Currently, there is a traditional treatment and a novel one that was ordered for the pediatric patient in this report.

Prevalência de hipofosfatemia e risco de síndrome de realimentação em idosos internados em uma unidade de terapia intensiva / Prevalence of hypophosphatemia and risk of refeeding syndrome in elderly patients admitted to an intensive care unit

Introdução: A presença de hipofosfatemia é fortemente relacionada à ocorrência de síndrome de realimentação em pacientes críticos, na qual um dos principais grupos de risco é a população idosa. Objetivos: Avaliar a prevalência de hipofosfatemia e o risco de síndrome de realimentação em idosos internados em uma unidade de terapia intensiva. Métodos: Estudo observacional prospectivo, realizado numa unidade de terapia intensiva com pacientes idosos de ambos os sexos e em uso de terapia nutricional enteral. Foram coletados dados demográficos, clínicos e exames bioquímicos, e realizadas triagem e avaliação nutricional. As necessidades nutricionais foram calculadas e adotou-se o ponto de corte de 90% para estabelecer a adequação da oferta calórica. Para avaliar o risco e a ocorrência de síndrome de realimentação, foram utilizados os critérios propostos pelo grupo NICE. A análise estatística foi realizada com o auxílio do programa SPSS 13.0, com um intervalo de confiança (IC) de 95%. Resultados: Foram estudados 44 pacientes, dos quais 34,1% estavam em magreza; 86,4% dos pacientes iniciaram a terapia nutricional enteral em até 48 horas, com 43,2% de adequação calórica em até 72 horas. A hipofosfatemia foi encontrada em 9,1% dos pacientes na admissão e em 29,5% após o início da dieta. Com isso, 88,6% dos pacientes apresentaram algum risco para desenvolver síndrome de realimentação e 40,9% deles manifestaram a síndrome. Conclusão: Foi identificada elevada prevalência de hipofosfatemia após o início da terapia nutricional. Além disso, o risco de desenvolver síndrome de realimentação foi elevado e sua manifestação se assemelha aos dados encontrados na literatura. (AU)

Introduction: The presence of hypophosphatemia is strongly related to the occurrence of refeeding syndrome in critically ill patients, in which one of the main risk groups is the elderly population. Objectives: To assess the prevalence of hypophosphatemia and the risk of refeeding syndrome in elderly patients admitted to an intensive care unit. Methods: Prospective observational study carried out in an intensive care unit with elderly patients of both genders using enteral nutritional therapy. Demographic, clinical and biochemical data were collected, and nutritional screening and assessment were performed. The energy and nutrient requirements were calculated and a cutoff point of 90% was adopted to establish the adequacy of the caloric supply. To assess the risk and occurrence of refeeding syndrome, the criteria proposed by the NICE group were used. Statistical analyses were performed using the SPSS 13.0 program, with a 95% confidence interval (CI). Results: 44 patients were studied, of which 34.1% were malnourished; 86.4% of patients started enteral nutritional therapy within 48 hours, with 43.2% of caloric adequacy within 72 hours. Hypophosphatemia was found in 9.1% of patients on admission and in 29.5% after starting the diet. Thus, 88.6% of patients had some risk of developing the refeeding syndrome and 40.9% of them manifested the syndrome. Conclusion: A high prevalence of hypophosphatemia was identified after starting nutritional therapy. In addition, the risk of developing refeeding syndrome was high and its manifestation is similar to data found in the literature. (AU)

Therapy for persistent hypercalcemic hyperparathyroidism post-renal transplant: cinacalcet versus parathyroidectomy / Tratamento do hiperparatireoidismo hipercalcêmico persistente pós-transplante renal: cinacalcete versus paratireoidectomia

ABSTRACT Background: Persistent hyperparathyroidism post-transplant is associated with increases in the incidence of cardiovascular events, fractures, and deaths. The aim of this study was to compare both therapeutic options available: parathyroidectomy (PTX) and the calcimimetic agent cinacalcet. Methods: A single center retrospective study including adult renal transplant recipients who developed hypercalcemia due to persistent hyperparathyroidism. Inclusion criteria: PTH > 65 pg/mL with serum calcium > 11.5 mg/dL at any time after transplant or serum calcium persistently higher than 10.2 mg/dL one year after transplant. Patients treated with cinacalcet (n=46) were compared to patients treated with parathyroidectomy (n=30). Follow-up period was one year. Clinical and laboratory data were analyzed to compare efficacy and safety of both therapeutic modalities. Results: PTX controlled calcemia faster (month 1 x month 6) and reached significantly lower levels at month 12 (9.1±1.2 vs 9.7±0.8 mg/dL, p < 0.05); PTX patients showed significantly higher levels of serum phosphate (3.8±1.0 vs 2.9±0.5 mg/dL, p < 0.05) and returned PTH to normal levels (45±51 pg/mL). Cinacalcet, despite controlling calcium and phosphate in the long term, decreased but did not correct PTH (197±97 pg/mL). The proportion of patients that remained with PTH above normal range was 95% in the cinacalcet group and 22% in the PTX group. Patients treated with cinacalcet had better renal function (creatinine 1.2±0.3 vs 1.7±0.7 mg/dL, p < 0.05). Conclusions: Surgical treatment was superior to cinacalcet to correct the metabolic disorders of hyperparathyroidism despite being associated with worse renal function in the long term. Cinacalcet proved to be a safe and well tolerated drug.

RESUMO Introdução: O hiperparatireoidismo persistente pós-transplante está associado a aumento na incidência de eventos cardiovasculares, fraturas e óbitos. O objetivo deste estudo foi comparar as opções terapêuticas disponíveis: paratireoidectomia (PTX) e o agente calcimimético cinacalcete. Métodos: Estudo retrospectivo de um único centro incluiu pacientes transplantados renais adultos que desenvolveram hipercalcemia devido a hiperparatireoidismo persistente. Critérios de inclusão: PTH > 65 pg/mL com cálcio sérico > 11,5 mg/dL a qualquer momento após o transplante, ou cálcio sérico persistentemente superior a 10,2 mg/dL um ano após o transplante. Os pacientes tratados com cinacalcete (n = 46) foram comparados aos pacientes tratados com paratireoidectomia (n = 30). O período de acompanhamento foi de um ano. Dados clínicos e laboratoriais foram analisados para comparar a eficácia e a segurança de ambas as modalidades terapêuticas. Resultados: a PTX controlou a calcemia mais rapidamente (mês 1 x mês 6) e atingiu níveis significativamente mais baixos no mês 12 (9,1 ± 1,2 v.s. 9,7 ± 0,8 mg/dL, p < 0,05); pacientes submetidos à PTX apresentaram níveis significativamente mais altos de fósforo sérico (3,8 ± 1,0 v.s. 2,9 ± 0,5 mg/dL, p < 0,05) e retornaram aos níveis normais de PTH (45 ± 51 pg/mL). O cinacalcete, apesar de controlar o cálcio e o fósforo no longo prazo, diminuiu, mas não corrigiu o PTH (197 ± 97 pg/mL). A proporção de pacientes que permaneceram com PTH acima da faixa normal foi de 95% no grupo cinacalcete e 22% no grupo PTX. Os pacientes tratados com cinacalcete apresentaram melhor função renal (creatinina 1,2 ± 0,3 v.s. 1,7 ± 0,7 mg/dL, p < 0,05). Conclusões: O tratamento cirúrgico foi superior ao cinacalcete para corrigir os distúrbios metabólicos do hiperparatireoidismo, apesar de estar associado a pior função renal no longo prazo. Cinacalcete provou ser um medicamento seguro e bem tolerado.

Hypophosphatemia and risk of refeeding syndrome in critically ill patients before and after nutritional therapy

Summary OBJECTIVE: To investigate the prevalence of hypophosphatemia as a marker of refeeding syndrome (RFS) before and after the start of nutritional therapy (NT) in critically ill patients. METHODS: Retrospective cohort study including 917 adult patients admitted at the intensive care unit (ICU) of a tertiary hospital in Cuiabá-MT/Brasil. We assessed the frequency of hypophosphatemia (phosphorus <2.5mg/dl) as a risk marker for RFS. Serum phosphorus levels were measured and compared at admission (P1) and after the start of NT (P2). RESULTS: We observed a significant increase (36.3%) of hypophosphatemia and, consequently, a greater risk of RFS from P1 to P2 (25.6 vs 34.9%; p<0.001). After the start of NT, malnourished patients had a greater fall of serum phosphorus. Patients receiving NT had an approximately 1.5 times greater risk of developing RFS (OR= 1.44 95%CI 1.10-1,89; p= 0.01) when compared to those who received an oral diet. Parenteral nutrition was more associated with hypophosphatemia than either enteral nutrition (p=0,001) or parenteral nutrition supplemented with enteral nutrition (p=0,002). CONCLUSION: The frequency of critically ill patients with hypophosphatemia and at risk for RFS on admission is high and this risk increases after the start of NT, especially in malnourished patients and those receiving parenteral nutrition.

RESUMO OBJETIVO: Determinar a frequência de hipofosfatemia como marcador da síndrome de realimentação (SR) antes e após o início da TN em pacientes críticos. MÉTODOS: Coorte retrospectiva realizada com 917 pacientes adultos de um hospital terciário em Cuiabá-MT. Foi determinada a frequência de hipofosfatemia (fósforo <2,5 mg/dl) como marcador de risco de SR, para valores de fósforo sérico da admissão (P1) e após o início da TN (P2). RESULTADOS: Foi observado um aumento significativo (36,3%) da hipofosfatemia entre P1 e P2 e, consequentemente, do risco de SR (25,6% vs 34,9%; p<0,001) com o início da TN. Após o início da TN, pacientes desnutridos apresentaram maior queda do fósforo sérico. Os pacientes com TN apresentaram aproximadamente 1,5 vez mais chance de desenvolver hipofosfatemia e risco de SR (OR=1,44 IC95% 1,10-1,89; p=0,01) quando comparado aos com dieta oral. Nutrição parenteral foi mais associada à hipofosfatemia versus nutrição enteral (p=0,001) e nutrição enteral suplementada com parenteral (p=0,002). CONCLUSÃO: A frequência de pacientes críticos com hipofosfatemia e em risco de SR é alta e esse risco aumenta após o início da TN, especialmente nos desnutridos e naqueles recebendo nutrição parenteral.

Variación en los niveles séricos de Calcio, Fósforo, Magnesio, Cobre y Zinc durante las distintas etapas productivas en cabras de leche en un tambo caprino del noroeste argentino / Variation in serum levels of Calcium, Phosphorous, Magnesium, Copper and Zinc across productive stages of dairy goats in northwestern Argentina

Resumen El objetivo de este trabajo fue evaluar los niveles séricos de calcio (Ca), fósforo (P), magnesio (Mg), cobre (Cu), y zinc (Zn) en cabras lecheras en diferentes etapas productivas. Se seleccionaron 20 cabras de raza Saanen en diferentes estadios productivos: preparto (1 a 2 semanas previas al parto), posparto (1 a 2 semanas de lactancia), pico de lactancia (6 a 8 semanas de lactancia posparto) y período de seca (15 a 30 días de finalizada la lactancia) de un establecimiento lechero del valle de Lerma, Salta. Se colectaron muestras de sangre y se midieron los niveles séricos de Ca, Mg, Cu, y Zn empleando espectrofotometría de absorción atómica y P por colorimetría. Se identificó hipocalcemia (7,7±0,2 mg/dL) e hipofosfatemia (3,4±0,4 mg/dL) durante todas las etapas productivas. El Mg, por el contrario, presentó niveles adecuados durante todo el ensayo (2,5±0,06 mg/dL). Con respecto a los microminerales evaluados, solo los niveles séricos de Zn fueron inferiores a los recomendaros en todos los periodos productivos (53±4 µg/dL). Los niveles de Cu estuvieron dentro de los límites normales (53±4 µg/dL). Estos resultados permitieron identificar anormalidades en los niveles de Ca, P y Zn durante los periodos productivos evaluados. La información sobre deficiencias minerales en cabras es escasa y debe estudiarse más al respecto.

Abstract The aim of this study was to evaluate the serum levels of calcium (Ca), phosphorus (P), magnesium (Mg), copper (Cu), and zinc (Zn) in dairy goats in different productive periods. Twenty Saanen breed goats were selected at different productive stages: prepartum (1 to 2 weeks before partum), postpartum (1 to 2 weeks of lactation), peak of lactation (6 to 8 weeks postpartum) and dry period (15 to 30 days of the final lactation) of a dairy farm in the Valle de Lerma, in the province of Salta. Blood samples were collected and then, Ca, Mg, Cu and Zn levels were measured using atomic absorption spectrophotometry, and P was measured by colorimetric. Hypocalcaemia (7,7±0,2 mg/dL) and hypophosphatemia (3,4±0,4 mg/dL) were found in all production stages. In contrast, Mg levels did not present variation during all the samplings (2.5 ± 0.06 mg / dL). In evaluated micro-minerals, only the serum levels of Zn were lower than those recommended in all the productive periods (53 ± 4 µg / dL). Serum cupper levels were within normal limits (53 ± 4 µg / dL). The obtained results allowed identifying abnormalities in Ca, P and Zn levels during the evaluated productive periods. Information about mineral deficiency in goats is restricted and it is needed to study more about it.

Asociación entre hipoalbuminemia e hipofosfatemia con desnutrición en pacientes con Enfermedad Renal Crónica en hemodiálisis / Association Between Hypoalbuminemia And Hypophosphatemia With Malnutrition In Patients With Chronic Renal Disease Undergoing Hemodialysis

Introducción: La malnutrición en los pacientes en hemodiálisis es consecuencia de diversos factorescarenciales e hipercatabólicos y constituye un factor de riesgo de morbimortalidad. Objetivo:Determinar la asociación entre hipoalbuminemia e hipofosfatemia con la escala de valoración globalsubjetiva (VGS) tipo C en pacientes con enfermedad renal crónica en hemodiálisis. Métodos: Estudiotransversal analítico. Se estudiaron pacientes del servicio de hemodiálisis del hospital GuillermoAlmenara. Para la asociación entre variables continuas de malnutrición y los tipos de VGS se utilizóel test de Kruskal-Wallis y prueba de comparaciones múltiples y para las variables categóricashipoalbuminemia (≤3,5 g/dL) e hipofosfatemia (<3 mg/dL) se utilizó el chi cuadrado. Se analizó laasociación con la VGS tipo C. Resultados: Se incluyeron 131 pacientes y la edad mediana fue de 63años. El 34% presentó hipoalbuminemia, 27% presentó hipofosfatemia y el 14% una VGA tipo C. El52% (68) de los pacientes presentó alteración de al menos un biomarcador analizado. Se encontrarondiferencias entre VGS y albúmina (p<0,001) y fósforo (p=0,040). Los pacientes con VGS tipo C tuvieronuna media de albúmina de 3,1±0,74 de fósforo de 2,88±1,54 y tuvieron diferencia significativa encomparación con los de VGS tipo A (p<0,001 y p=0,011, respectivamente). El análisis de chi cuadradotambién demostró asociación significativa entre VGS e hipoalbuminemina (p=0,017) e hipofosfatemia(p=0,050). Conclusión: Existe asociación entre la VGS tipo C e hipoalbuminemia e hipofosfatemia enpacientes con enfermedad renal crónica en hemodiálisis.

Introduction: Malnutrition in hemodialysis patients is a consequence of various deficiency andhypercatabolic factors and constitutes a risk factor for morbidity and mortality. Objective: Determinethe association between hypoalbuminemia and hypophosphatemia with the Subjective globalassessment (SGA) C in patients with chronic renal disease on hemodialysis. Methods: Analytical cross-sectional study. Patients from the hemodialysis service of the Hospital Guillermo Almenara werestudied. The Kruskal-Wallis test and multiple comparisons test were used for the association betweencontinuous variables of malnutrition and the types of SGA. The square-chi test was used for thecategorical variables hypoalbuminemia (≤3.5 g/dL) and hypophosphatemia (<3 mg/dL). The associationwith SGA C was analyzed. Results: 131 patients were included and the median age was 63 years. 34%had hypoalbuminemia, 27% had hypophosphatemia and 14% had SGA C. 52% (68) of the patientspresented alteration of at least one analyzed biomarker. Differences were found between SGA andalbumin (p<0.001) and phosphorus (p=0.040). Patients with SGA C had a mean albumin of 3.1±0.74 andphosphorus of 2.88±1.54 and had a significant difference compared to those with SGA A (p<0.001 and P= 0.011, respectively). Chi-square analysis also demonstrated a significant association between SGA andhypoalbuminemia (p = 0.017) and hypophosphatemia (p=0.050). Conclusion: There is an associationbetween SGA C and hypoalbuminemia and hypophosphatemia in patients with chronic kidney diseaseundergoing hemodialysis.

Risk of refeeding syndrome. case report

ABSTRACT Introduction: Refeeding syndrome (RS) is an acute metabolic disorder that occurs during nutritional repletion. Although it has been known for years, the early detection of risk factors for its onset and the implementation of measures to prevent it are not common in nutritional care. Case presentation: 48-year-old male patient, in critical care for 6 days, with suspected Wernicke-Korsakoff encephalopathy and high risk of refeeding syndrome according to criteria of the United Kingdom National Institute of Health and Clinical Excellence. The subject received enteral nutrition with 14 kcal/kg for the first 3 days, with subsequent increases aiming to achieve a nutritional goal of 25 kcal/kg on day 5. He also received daily supplementation of thiamine 600mg, folic acid 5mg and pyridoxine 50mg. Blood phosphorus decreased from 3 mg/dL to 2 mg/dL the day after initiating the nutritional plan and normalized by day 3. Discussion: The patient did not present severe hypophosphatemia or clinical manifestations of refeeding syndrome. Hypophosphatemia was resolved by maintaining a stable caloric restriction during the first days. Some professionals consider this restriction as very conservative, and others think that it may lead to achieve significant improvements in mortality reduction. Conclusions: The strategy for assessing the risk of refeeding syndrome, nutritional management and implemented follow-up were successful in preventing the patient from developing a refeeding syndrome.

RESUMEN Introducción. El síndrome de realimentación (SR) es un trastorno metabólico agudo que ocurre durante la repleción nutricional. Aunque ha sido conocido por años, la detección precoz de factores de riesgo para su desarrollo y la instauración de medidas para prevenirlo no son una práctica habitual en la atención nutricional. Presentación del caso. Paciente masculino de 48 años en cuidado crítico por 6 días, con sospecha de encefalopatía de Wernicke-Korsakoff y riesgo alto de SR según criterios del Instituto Nacional de Salud y Excelencia Clínica del Reino Unido. El sujeto recibió nutrición enteral con 14 kcal/kg los 3 primeros días, con aumentos posteriores que pretendían una meta de 25 kcal/kg al día 5 y suplementación diaria de tiamina 600mg, ácido fólico 5mg y piridoxina 50mg. El fósforo en sangre disminuyó de 3 mg/dL a 2 mg/dL al día siguiente del inicio de la nutrición y se normalizó para el día 3. Discusión. El paciente no presentó manifestaciones clínicas de SR ni hipofosfatemia severa; esta última se resolvió manteniendo estable la restricción calórica los primeros días. Para algunos profesionales dicha restricción puede ser muy conservadora; sin embargo, para otros puede llevar a mejoras significativas en la reducción de la mortalidad. Conclusiones. La estrategia para valorar el riesgo de SR, el manejo nutricional y el seguimiento implementado fueron acertados para evitar que el paciente desarrollara el síndrome.

Uveítis anterior aguda asociada a raquitismo renal hipofosfatémico / Acute anterior uveítis associated to hypophosphatemic renal ricketts

Los raquitismos hipofosfatémicos hereditarios son un grupo de enfermedades caracterizadas por la pérdida renal de fosfatos. Cursan con hipocrecimiento disarmónico y deformidades óseas. La forma más común es el raquitismo hipofosfatémico ligado al cromosoma X, el cual es causado por mutaciones inactivantes en el gen PHEX. El objetivo de nuestro trabajo fue describir las alteraciones oculares encontradas y la evolución clínica en un paciente con raquitismo hipofosfatémico hereditario y uveítis anterior. Se presenta un niño de 9 años de edad con diagnóstico de raquitismo hipofosfatémico hereditario, valorado en el Servicio de Uveítis del Instituto Cubano de Oftalmología Ramón Pando Ferrer por presentar dolor ocular y molestias a la luz en el ojo derecho. En la exploración oftalmológica se constata una uveítis anterior con hipopión en el ojo derecho y depósitos de cristales en todo el espesor corneal y el iris en ambos ojos. Se indicaron esteroides tópicos con resolución del proceso inflamatorio. Los hallazgos en el segmento anterior del paciente son sugestivos de cistinosis, donde el acúmulo de cristales es la alteración corneal más típica de las manifestaciones oculares, con una incidencia del 90 por ciento en niños menores de un año, y los primeros órganos afectados son los riñones. Los raquitismos hipofosfatémicos hereditarios pueden cursar con depósitos de cristales corneales y procesos inflamatorios de la úvea anterior(AU)

Hereditary hypophosphatemic rickets are a group of diseases characterized by renal loss of phosphates. They appear with disharmonic hypogrowth and bone deformities. The most common form is the X-chromosome-linked hypophosphatemic rickets which is caused by inactivating mutations in PHEX gene. The objective of our work was to describe the ocular alterations and the clinical evolution in a patient with hereditary hypophosphatemic rickets and previous uveitis. Here is the case of a 9 years-old boy diagnosed with hereditary hypophosphatemic rickets, who was seen at the Uveitis Service of Ramon Pando Ferrer Cuban Institute of Ophthalmology. He presented with ocular pain and feeling of discomfort to light in his right eye. The ophthalmological exam yielded anterior uveitis with hypopyon in his right eye and crystal depots in the whole corneal thickness and the iris of both eyes. Topical steroids were prescribed to treat the inflammatory process. The findings in the anterior segment of the patients indicated the presence of cystinosis in which the accumulation of crystals is the most typical corneal alteration among the ocular manifestations. Its incidence reaches 90 percent in under one year-old children and the first affected organs are the kidneys. The hereditary hypophosphatemic rickets may appear with corneal crystal depots and inflammatory processes in the anterior uvea(AU)

La alimentación con lactancia materna exclusiva es un factor de riesgo para osteopenia en prematuros menores de 1500 gramos y menores de 32 semanas de gestación en comparacion leche materna fortificada o leche de fórmula / Exclusive breastfeeding is a risk factor for osteopenia in preterm infants under 1500 grams and under 32 weeks of gestation compared to fortified breast milk or formula milk

Contexto: La osteopenia o enfermedad ósea metabólica del prematuro, consiste en una mineralización ósea insuficiente de origen multifactorial que afecta principalmente a recién nacidos pretérminos. Propósito: Determinar si la leche materna exclusiva es un factor de riesgo de osteopenia en prematuros menos de 1500 gramos y menos de 32 semanas de gestación. Material y métodos: Estudio descriptivo, epidemiológico, observacional, transversal de dos cohortes para comparar la osteopenia entre aquellos que consumen leche materna exclusiva versus los que reciben alimentación mixta (leche materna-leche de fórmula). Población 406 casos ingresados en Unidad de cuidados intensivos neonatales del Hospital Docente de Calderón- Hospital Roberto Gilbert Elizalde de Abril - Noviembre 2018. Muestra 209 prematuros. Resultados: Se analizaron 209 prematuros de bajo peso < 1.500 gramos y con edad gestacional < 32 semanas de gestación que fueron alimentados con leche materna o mixta, sexo femenino (n=109; 52,15%) y sexo masculino (n= 100; 47,85%); recibieron leche materna exclusiva (n=99; 47,37%), mientras que el (n=110; 52,63%) recibieron lactancia mixta. Se comparó los parámetros bioquímicos que forman parte del perfil de osteopenia entre los prematuros de bajo peso con lactancia materna versus lactancia mixta; los resultados muestran diferencias significativas para todos los parámetros con p-valor de 0,000; donde para el calcio la media fue de 9,23 mg en lactancia materna y 10,43 mg en mixta; la media del fósforo se ubicó en 2,94 mg en lactancia materna y 4,71 mg en mixta; por último la fosfatasa alcalina presentó promedio de 651,85 UI/L en lactancia materna y 395,51 UI/L en mixta; siendo significativas las diferencias entre estos grupos con p-valor 0,000. Conclusión: Los prematuros que recibieron leche materna exclusiva presentan mayor riesgo de desarrollar osteopenia en relación con los prematuros que recibieron lactancia mixta.

Context: Osteopenia or metabolic bone disease of prematurity, consists of an insufficient bone mineralization of multifactorial origin that mainly affects preterm newborns. Purpose: To determine if exclusive breast milk is a risk factor for osteopenia in premature babies less than 1500 grams and less than 32 weeks of gestation. Material and methods: A descriptive, epidemiological, observational, cross-sectional study of two cohorts to compare osteopenia between those who consume exclusive breast milk versus those who receive mixed feeding (breast milk-formula milk). Population 406 cases admitted to the Neonatal Intensive Care Unit of the Teaching Hospital of Calderón Hospital Roberto Gilbert Elizalde in April - November 2018. It shows 209 premature infants. Results: We analyzed 209 premature infants of low weight <1,500 grams and with gestational age <32 weeks of gestation that were fed with breast milk or mixed, female sex (n = 109, 52.15%) and male sex (n = 100; 47.85%); they received exclusive breast milk (n = 99, 47.37%), while (n = 110, 52.63%) received mixed breastfeeding. We compared the biochemical parameters that are part of the profile of osteopenia among low birth weight premature infants with breastfeeding versus mixed lactation; the results show significant differences for all parameters with p-value of 0.000; where for calcium the average was 9.23 mg in breastfeeding and 10.43 mg in mixed; the average phosphorus was 2.94 mg in breastfeeding and 4.71 mg in mixed; finally, alkaline phosphatase presented an average of 651.85 IU / L in breastfeeding and 395.51 IU / L in mixed; being significant the differences between these groups with p-value 0.000. Conclusion: Preterm infants who received exclusive breast milk presented a higher risk of developing osteopenia in relation to preterm infants who received mixed breastfeeding.

Raquitismo hipofosfatêmico: relato de caso / Hypophosphatemic rickets: case report

RESUMO Objetivo: O raquitismo hipofosfatêmico precisa ser precocemente diagnosticado porque seu tratamento previne sequelas incapacitantes. Este relato alerta para a doença. Relato de caso: Relato de perfil metabólico, depuração de creatinina, estado nutricional e desenvolvimento pôndero-estatural de paciente com características clínico-laboratoriais de raquitismo hipofosfatêmico, atendido em ambulatório de tubulopatias por período de 12 meses. Chegou ao serviço após tempo prolongado acamado, dependente de ventilação mecânica e com perfil metabólico ósseo alterado. Terapêutica consistiu na administração de fósforo (inicial: 65 mg/kg/dia, final: 24,2 mg/kg/dia), cálcio (inicial: 127 mg/kg/dia, final: 48,4 mg/kg/dia) e calcitriol (inicial: 0,06 mcg/kg/dia, final: 0,03 mcg/kg/dia), e a análise constou da descrição das consultas, utilizando-se mediana de exames laboratoriais e dados antropométricos. Observou-se nítida melhora inicial do padrão respiratório do paciente, que evoluiu com ventilação espontânea e deambulação autônoma; com exames laboratoriais: cálcio (mg/dL) inicial 7,1, final 10,1; fósforo (mg/dL) inicial 1,7, final 3,2; magnésio (mg/dL) inicial 1,5, final 2,1; paratormônio (pg/L) inicial 85,8, final 52,7; fosfatase alcalina (UI/L) inicial 12660, final 938; e melhora do desenvolvimento pôndero-estatural (escore Z: E/I inicial: -6,05, final -3,64; P/I: inicial -2,92, final -1,57) com presença de litíase transitória. A depuração de creatinina (mL/min/1,73 m2sc) foi constante durante o seguimento. O tratamento propiciou benefícios clínicos, bioquímicos e nutricionais, mas, apesar da boa resposta inicial, a família abandonou o seguimento por dois anos, apresentando o paciente piora da deambulação e das deformidades esqueléticas. Comentários: Não apenas diagnóstico precoce é necessário, como também a adesão ao tratamento é fundamental para o sucesso na condução dessa patologia.

ABSTRACT Objective: Early diagnosis and immediate treatment of hypophosphatemic rickets is of utmost importance as it may prevent subsequent sequelae. This report aims at warning pediatricians to consider the presence of the disease. Case description: Description of the metabolic profile, creatinine clearance, nutritional status, weight and body structure of a patient who presented the clinical-laboratorial characteristics of hypophosphatemic rickets and was followed in an outpatient clinic for tubulopathies over the period of 12 months. The patient had been bedridden for some time, was dependent on mechanical ventilation and presented an altered metabolic bone condition. Treatment was phosphate (initial: 65 mg/kg/day and final: 24,2 mg/kg/day), calcium (initial: 127 mg/kg/day, final: 48,4 mg/kg/day) and calcitriol (initial: 0.06 mcg/kg/day, final: 0.03 mcg/kg/day). The patient improved, evolving into spontaneous breathing and walking unaided. Laboratory results: calcium (mg/dL) initial 7.1, final 10.1; phosphate (mg/dL) initial 1.7 final 3.2; magnesium (mg/dL) initial 1.5 final 2.1, parathyroid hormone (pg/l) initial 85.8, final 52.7, alkaline phosphatase (UI/l) initial 12660, final 938; there was also improvement in weight/structural development (Z score: H/A initial: -6.05, final -3.64; W/A: initial -2.92, final -1.57) with presence of transitory gallstones. Creatinine clearance (mL/min/1.73m2bsa) was constant. The medication improved his laboratory results and nutritional status, but the patient did not return for two years for follow-up and, during this period, his condition has noticeably deteriorated. Comments: Early diagnosis and follow-up are essential in dealing with this pathology.

Hipercalcemia e hipofosfatemia en prematuros que reciben nutrición parenteral agresiva / Hypercalcemia and hypophosphatemia among preterm infants receiving aggressive parenteral nutrition

Introducción. La nutrición parenteral agresiva constituye un estándar de cuidado en prematuros de muy bajo peso. Sin embargo, investigaciones recientes evaluaron su impacto en los resultados a corto plazo, como la homeostasis mineral y electrolítica. El objetivo fue comparar la prevalencia de hipercalcemia e hipofosfatemia en prematuros que recibían nutrición parenteral agresiva o estándar. Métodos. Estudio observacional retrospectivo que comparó a un grupo de prematuros menores de 1250 gramos que recibían nutrición parenteral agresiva con un grupo control histórico. Se calculó la prevalencia de hipercalcemia y se buscó la asociación con nutrición parenteral agresiva ajustando por confundidores. Se estimó la media de fosfatemia del grupo control mediante regresión lineal y se la comparó con el otro grupo. Resultados. Se incluyeron 40 pacientes por grupo. La prevalencia de hipercalcemia fue mayor en el grupo de nutrición parenteral agresiva (87,5% vs. 35%, p= 0,001). La nutrición parenteral agresiva se asoció con hipercalcemia al ajustar por peso al nacer, restricción del crecimiento intrauterino, aporte de aminoácidos y calorías (ORa 21,8; IC 95%: 3,7-128). La media de calcemia fue diferente entre ambos grupos (p= 0,002). El grupo de nutrición parenteral agresiva presentó más sepsis sin alcanzar significancia estadística y su fosfatemia media resultó menor que la estimada para el grupo control (p= 0,04). La prevalencia de hipofosfatemia en este grupo fue de 90% (IC 95%: 76-97%). Conclusiones. Nuestros datos muestran una asociación entre hipercalcemia/hipofosfatemia y nutrición parenteral agresiva. Se recomienda monitorizar la calcemia y la fosfatemia frecuentemente, ya que pueden estar asociadas con resultados clínicos adversos.

Introduction. Aggressive parenteral nutrition is the standard of care among very-low-birth weight preterm infants. However, in recent studies, its impact on short-term outcomes, has been evaluated. The objective was to compare the prevalence of hypercalcemia and hypophosphatemia among preterm infants receiving aggressive or standard parenteral nutrition. Methods. Observational, retrospective study comparing a group of preterm infants weighing less than 1250 grams who received aggressive parenteral nutrition with a historical control group. The prevalence of hypercalcemia was estimated and its association with aggressive parenteral nutrition was searched adjusting by confounders. The mean phosphate level was estimated for the control group by linear regression and was compared to the value in the other group. Results. Forty patients per group were included. The prevalence of hypercalcemia was higher in the group who received aggressive parenteral nutrition (87.5% versus 35%, p= 0.001). Aggressive parenteral nutrition was associated with hypercalcemia when adjusting by birth weight, intrauterine growth restriction, amino acid, and calorie intake (adjusted odds ratio: 21.8, 95% confidence interval -amp;#91;CI-amp;#93;: 3.7-128). The mean calcium level was different between both groups (p= 0.002). Infants who received aggressive parenteral nutrition had more sepsis without reaching statistical significance and the mean phosphate level was lower than that estimated for the control group (p= 0.04). The prevalence of hypophosphatemia in this group was 90% (95% CI: 76-97%). Conclusions. Our data show an association between hypercalcemia/hypophosphatemia and aggressive parenteral nutrition. It is recommended to frequently monitor calcium and phosphate levels since they might be associated with adverse clinical outcomes.

Hipofosfatemia y su relación con el inicio del soporte nutricional en pacientes críticos / Hypophosphatemia and its relationship with the start of nutritional support in critical patients

Objetivos: Establecer la relación entre el inicio del soporte nutricional y el desarrollo de hipofosfatemia. Determinar la incidencia de hipofosfatemia, evaluar el desarrollo de hipofosfatemia en pacientes clasificados "en riesgo" de desarrollar síndrome de realimentación según la guía NICE, relacionar hipofosfatemia y gravedad de la enfermedad mediante el puntaje APACHE II. Materiales y Métodos: Estudio analítico, observacional y retrospectivo, que evaluó la determinación plasmática seriada antes del inicio del soporte nutricional y al primer día de este, en 61 enfermos críticos. Los pacientes fueron clasificados como "con riesgo" o "sin riesgo" de desarrollar síndrome de realimentación según la guía NICE y se calculó el puntaje APACHE II. El análisis se llevó a cabo con las prueba t de Student y correlación lineal para datos cuantitativos, y ji al cuadrado para datos cualitativos. Se consideraron estadísticamente significativos valores p<0,05. Resultados: El nivel de fosfato del día 0 sin alimentación al día 1 del soporte nutricional disminuyó significativamente (p = 0,001). La incidencia de hipofosfatemia al día 1 fue del 6% y la de hipofosfatemia grave, 2,6%. La clasificación mediante la guía NICE no produjo diferencia significativa en el valor de fosfato (p = 0,103). No se halló asociación entre hipofosfatemia y puntaje APACHE II (p = 0,73). Conclusiones: La disminución del nivel de fosfato en pacientes críticos al comienzo del soporte nutricional manifiesta la relación de este ion con el inicio de la alimentación. La hipofosfatemia no fue condicionada por la clasificación "en riesgo" según la guía NICE o la gravedad de la enfermedad por APACHE II. Estos hallazgos confirman la importancia del monitoreo periódico de los valores de fosfato y de aquellos factores de riesgos que puedan conducir a su disminución(AU)

Objectives: Establish the relationship between onset of nutritional support and development of hypophosphatemia.To determine the incidence of hypophosphatemia and assess development of hypophosphatemia in patients classified as "at risk" of refeeding syndrome according to NICE guide. To relate hypophosphatemia and severity of the disease through APACHE II score. Materiales and Methods: Analytical, observational and retrospective study to evaluate the serial laboratory results before nutritional support and the first day of it in 61 critically ill patients. Patients were classified as "at risk" or "not at risk" of developing refeeding syndrome according to NICE guide and APACHE II score. Analysis of quantitative data was performed using Student t test and linear correlation; chi-squared test was used for qualitative data. A value of p<0.05 was considered statistically significant. Results: Phosphate level without food on day 0 to day 1 of nutritional support decreased significantly (p=0.001). The incidence of hypophosphatemia to day 1 was 6% and that of severe hypophosphatemia was 2.6%. NICE guide classification produced no significant difference in the level of phosphate (p=0.103). No association between hypophosphatemia and APACHE II score (p=0.73) was found. Conclusiones: The decreased level of phosphate found at the start of nutritional support in critically ill patients shows the relationship of this ion with the start of feeding. Hypophosphatemia was not conditioned by "at risk" classification according to the NICE guide or the severity of the disease according to APACHE II score. These findings confirm the importance of regular monitoring of phosphate and those risk factors that could lead to its decline(AU)

Persistent disorders of mineral metabolism after one year of kidney transplantation / Alterações do metabolismo mineral e ósseo após um ano de transplante renal

Abstract Introduction: The persistence of mineral metabolism disorders after renal transplant (RT) appears to possess a negative impact over graft and patient's survival. Objectives: To evaluate the parameters of mineral metabolism and the persistence of hyperparathyroidism (HPT) in transplanted patients for a 12-month period after the procedure. Methods: Retrospective analysis of 41 transplants (18 women- 44%, mean age of 39 ± 15 years) performed in a University Hospital, evaluating changes of calcium (Ca), phosphorus (P) and parathyroid hormone (PTH) and the prevalence of persistent HPT. The patients were divided into two groups accordingly to PTH levels prior to Tx: Group 1 with PTH ≤ 300 pg/mL (n = 21) and Group 2 with PTH > 300 pg/mL (n = 20). The persistency of HPT after transplant was defined as PTH ≥ 100 pg/mL. The evolution of biochemical parameters and the persistency of HPT were analyzed in each group after 1 year of transplant. Results: After a one-year of follow up, 5% of the patients presented hypophosphatemia (p < 2.7 mg/dL), 24% hypercalcemia (Ca > 10.2 mg/dL) and 48% persistency of HPT (PTH ≥ 100 pg/mL). There was a positive correlation between the PTH pre and post Tx (r = 0.42/p = 0.006) and a negative correlation between PTH and Ca pre-Tx (r = -0.45/p = 0.002). However, there was no significant difference among groups 1 and 2 regarding PTH levels pre and post Tx. Conclusion: The findings in this article suggest that mineral metabolism alterations and the persistency of HPT may occur after one year of renal Tx, mainly in patients which present high PTH levels prior toTx.

Resumo Introdução: A persistência de distúrbios do metabolismo mineral ósseo após o transplante renal (Tx) parece possuir um impacto negativo sobre a sobrevida do enxerto e do paciente. Objetivos: avaliar os parâmetros do metabolismo mineral e a persistência de hiperparatiroidismo (pHPT) 12 meses após o Tx. Métodos: Análise retrospectiva de 41 transplantes (18 mulheres- 44%, idade de 39 ± 15 anos) realizados em um Hospital Universitário, avaliando cálcio (Ca), fósforo (P), hormônio da paratireóide (PTH) e a prevalência de pHPT. Pacientes foram divididos em dois grupos de acordo com os níveis de PTH pré Tx: Grupo 1: PTH ≤ 300 pg/ml (n = 21) e Grupo 2: PTH > 300 pg/ml (n = 20). pHPT foi definida como PTH ≥ 100pg/mL após o Tx. A evolução dos parâmetros bioquímicos e a pHPT foram analisadas após 1 ano de Tx. Resultados: após um ano, 5% dos pacientes apresentaram hipofosfatemia (p < 2,7mg/dL), 24% hipercalcemia (Ca > 10,2 mg/dL) e 48% persistência de HPT (PTH ≥ 100 pg/mL ). Houve correlação positiva entre PTH pré e pós Tx (r = 0,42/p = 0,006) e correlação negativa entre PTH e Ca pré-Tx (r = -0,45/p = 0,002). Entretanto, não houve diferença significativa entre os grupos 1 e 2 em relação aos níveis de PTH pré e pós-Tx. Conclusão: Os resultados sugerem que alterações do metabolismo mineral e a pHPT podem ocorrer após um ano do Tx, principalmente em pacientes com níveis elevados de PTH pré-Tx.

Tumores indutores de osteomalácia: diagnóstico, caracterização tumoral e avaliação evolutiva em longo prazo de nove pacientes / Tumor-induced osteomalacia: diagnosis, tumor characterization, and clinical evaluation in nine patients over a long-term period

Tumores indutores de osteomalácia (TIOs) são raros, geralmente apresentam origem mesenquimal, têm produção excessiva de fosfatoninas sendo a mais comum o FGF23 (Fibroblast Growth Factor 23) que, em níveis elevados, provoca osteomalácia hipofosfatêmica. A cura dos TIOs envolve a remoção completa do tumor, o que torna essencial sua localização. OBJETIVOS: (1) caracterizar nove pacientes com TIO ao diagnóstico e avaliá-los evolutivamente em longo prazo; (2) avaliar a eficácia da cintilografia com Octreotida (Octreoscan®) e a da cintilografia de corpo inteiro com Mibi (MIBI) na detecção dos TIOs. MÉTODOS: O acompanhamento dos pacientes consistiu na avaliação clínica, na avaliação laboratorial com ênfase no metabolismo ósseo e na realização de exames de imagem para caracterização das deformidades esqueléticas. Para a localização dos TIOs, os pacientes foram submetidos a exames de Octreoscan®, MIBI, ressonância magnética (RM) e tomografia computadorizada (TC). RESULTADOS: O período de observação dos pacientes variou de dois a 25 anos. Ao diagnóstico, todos exibiam fraqueza muscular, dores ósseas e fraturas de fragilidade. Em relação à avaliação laboratorial, apresentavam: hipofosfatemia com taxa de reabsorção tubular de fosfato reduzida, fosfatase alcalina aumentada e níveis elevados de FGF23. O Octreoscan® permitiu a identificação dos TIOs nos nove pacientes e o MIBI possibilitou a localização dos TIOs em seis pacientes, sendo que ambos os exames foram concordantes entre si e com os exames topográficos (RM ou TC). Os achados histopatológicos das lesões dos nove pacientes confirmaram tratar-se de oito tumores mesenquimais fosfatúricos (PMTs) benignos e um PMT maligno. Após a primeira intervenção cirúrgica para a remoção dos TIOs, quatro pacientes encontram-se em remissão da doença e cinco evoluíram com persistência tumoral. Dos cinco, quatro foram reoperados e um aguarda nova cirurgia. Dos que foram reoperados, um paciente se mantém em remissão da...

Tumor-induced osteomalacia (TIO) is rare. The tumor usually has mesenchymal origin and produces excessive phosphatonins, most commonly FGF23 (Fibroblast Growth Factor 23), which at high levels causes hyphophostatemic osteomalacia. The cure for TIO is achieved through complete removal of the tumor. It is therefore essential identify its location. OBJECTIVES: (1) to characterize nine patients with TIO at diagnosis and to evaluate their follow-up over a long-term period; (2) to evaluate the efficacy of whole-body scintigraphy 111In-octreotide (Octreoscan®) and 99mTc-sestamibi (MIBI) in TIO detection. METHODS: Evaluations consisted of clinical and laboratory testing of bone metabolism and imaging to characterize skeletal deformities. To locate TIO, patients underwent Octreoscan®, MIBI, magnetic resonance (MRI), and computed tomography (TC). RESULTS: Patients were followed-up from two to 25 years. At diagnosis, all patients presented with muscle weakness, bone pain and fragility fractures. Laboratorial evaluation revealed hypophosphatemia with reduced tubular reabsorption of phosphate, increased alkaline phosphatase, and high levels of FGF23. TIO was identified in nine patients through Octreoscan® and in six patients through MIBI. Results of both types of scintigraphies matched one another as well with topographic examination (MR or CT). Histopathological findings of the lesions in the nine patients confirmed the existence of eight benign phosphaturic mesenchymal tumors (PMTs) and one malign PMT. After the first surgery for tumor resection, four patients were in remission, whereas five revealed tumoral persistence. Four of the latter five were re-operated, and one is still waiting for another surgery. Of those four patients, one became in remission, one died of clinical complications, one disclosed metastatic disease, and the last one had tumoral recurrence three years after the second surgery. Severe bone deformations were observed in patients whose...

Osteomalacia oncogénica: Presentación de dos casos

La osteomalacia oncogénica es una enfermedad rara. Existen descriptos alrededor de 337 casos. Es ocasionada por un tumor productor del factor de crecimiento fibroblástico 23 (FGF-23), hormona que disminuye la reabsorción tubular de fosfatos y altera la hidroxilación renal de la vitamina D, con hipofosfatemia, hiperfosfaturia y niveles bajos de calcitriol. Se presentan dos pacientes de 44 y 70 años, que consultaron por dolores óseos generalizados de aproximadamente un año de evolución en los que se hallaron alteraciones bioquímicas compatibles con osteomalacia hipofosfatémica. En el primer caso se realizó la resección de una tumoración en tejido celular subcutáneo del pie derecho, un año después del diagnóstico clínico. Luego de la exéresis, se disminuyó el aporte de fosfatos que recibía el paciente, pero reaparecieron los dolores al intentar suspenderlos. Ocho años más tarde, hubo recidiva local de la tumoración por lo que se efectuó resección completa. Después de la misma, se logró suspender el aporte de fosfatos. En el segundo caso, el paciente se estudió con tomografía por emisión de positrones con 18F-fluorodesoxiglucosa, hallando formación nodular hipermetabólica en partes blandas de antepie derecho, de 2.26 cm de diámetro. Luego de su escisión se pudo suspender el aporte de fosfatos. Ambos pacientes se encuentran asintomáticos con indicadores de metabolismo fosfocálcico normales. El diagnóstico anatomopatológico en ambos fue un tumor mesenquimático fosfatúrico, variante mixta del tejido conectivo, la entidad más frecuentemente asociada a la osteomalacia oncogénica.

Oncogenic osteomalacia is a rare disease. It is caused by a tumor that produces fibroblast growth factor 23, a hormone that decreases the tubular phosphate reabsorption and impairs renal hydroxylation of vitamin D. This leads to hyperphosphaturia with hypophosphatemia and low calcitriol levels. About 337 cases have been reported and we studied two cases; 44 and 70 year-old men who sought medical attention complaining of suffering diffuse bone pain over a period of approximately one year. In both cases, a laboratory test showed biochemical alterations compatible with a hypophosphatemic osteomalacia. In the first case, a soft tissue tumor of the right foot was removed, one year after the diagnosis. The patient was allowed to diminish the phosphate intake, but symptoms reappeared at this time. Eight years later, a local recurrence of the tumor was noted. A complete excision was now performed. The patient was able to finally interrupt the phosphate intake. In the second case, an F-18 fluorodeoxyglucose positron emission tomography, with computed tomography revealed a 2.26 cm diameter hypermetabolic nodule in the soft tissue of the right forefoot. After its removal, the patient discontinued the phosphate intake. Both patients are asymptomatic and show a regular phosphocalcic laboratory evaluation. The histopathological diagnosis was, in both cases, a phosphaturic mesenchymal tumor, a mixed connective tissue variant. This is the prototypical variant of these tumors.

Tumor-induced osteomalacia: the importance of early diagnosis / Osteomalácia induzida por tumor: a importância do diagnóstico precoce

Tumor-induced osteomalacia is a rare paraneoplasic syndromethat can be completely cured with the removal of the culprittumor. This study described the clinical history of a patientaffected by tumor-induced osteomalacia. The patient was a57-year-old female who sought hospital due to intense andprogressive pain in the lower limbs and muscle weakness, aswell diffuse osteoporosis and a variety of pathologic fracturesat radiographs. Laboratory tests revealed hypophosphatemiawith hyperphosphaturia and raised the hypothesis of tumorinducedosteomalacia. Whole-body technetium-99m octreotidescintigraphy revealed the presence of a focal area of radiotraceruptake in the medial region of the left tarsus. After tumorexcision, there was a rapid correction of serum phosphorus,reduction of musculoskeletal complaints and evidence of bonehealing. Despite the diagnosis and treatment, the patient hadan unfavorable clinical outcome; she developed sepsis frompulmonary focus, evolving into refractory septic shock anddeath. We stress the need for greater recognition of tumorinducedosteomalacia as a cause of clinical bone pain, fractures,osteopenia and muscle weakness, superimposed on thecharacteristic biochemical profile with hypophosphatemia andrelative hyperphosphaturia. Greater awareness of the disease willallow earlier diagnosis and ultimately a greater curative potentialfor patients afflicted with this syndrome.(AU)

Osteomalácia induzida por tumor é uma síndrome paraneoplásicarara que pode ser curada completamente com a ressecção dotumor causador. Este estudo descreveu a história clínica de umapaciente afetada pela osteomalácia induzida por tumor. Paciente,de 57 anos, deu entrada no hospital por dor em membros inferiores,e fraqueza muscular intensa e progressiva, assim comoosteoporose difusa e fraturas patológicas. Exames laboratoriaisevidenciaram hipofosfatemia com hiperfosfatúria e levantarama hipótese de osteomalácia induzida por tumor. Cintilografia detodo corpo com tecnécio-99m revelou a presença de área focalde captação do radiofármaco na região medial do tardo esquerdo.Após a ressecção do tumor, houve rápida correção do fósforosérico, redução das queixas musculoesqueléticas e evidência decalo ósseo. Apesar de diagnóstico e tratamento, a paciente apresentouum desfecho clínico desfavorável, desenvolvendo sepsede foco pulmonar, choque séptico e evoluindo a óbito. Nós enfatizamosa necessidade de maior reconhecimento da osteomaláciainduzida por tumor como causa de dor óssea, fraturas patológicas,osteopenia e fraqueza muscular, superpostos a um perfilbioquímico característico, com hipofosfatemia e hiperfosfatúriarelativa. Maior alerta sobre a doença permitirá um diagnósticomais precoce e maior potencial curativo aos pacientes afetadospor essa síndrome.(AU)

Raquitismos hipofosfatémicos hereditarios / Hereditary hypophosphatemic rickets

Los raquitismos hipofosfatémicos hereditarios (RHH) son un grupo de enfermedades caracterizadas por la pérdida renal de fosfatos, que ocasionan retardo del crecimiento, raquitismo y osteomalacia. La forma más común es el raquitismo hipofosfatémico ligado al cromosoma X, el cual es causado por mutaciones inactivantes en el gen PHEX. Las otras formas de los síndromes hipofosfatémicos hereditarios presentan menor prevalencia. Estas incluyen el raquitismo hipofosfatémico autosómico dominante, el raquitismo hipofosfatémico autosómico recesivo tipos 1 y 2 y el raquitismo hipofosfatémico hereditario con hipercalciuria. En este artículo se revisan las bases genéticas de los diferentes tipos de RHH, las manifestaciones clínicas, las características bioquímicas en sangre y orina y los nuevos aspectos de su tratamiento.

Hereditary hypophosphatemic rickets (HHR) are a group of diseases characterized by renal phosphate wasting causing growth retardation, rickets and osteomalacia. The most common form is the X-linked dominant hypophosphatemic rickets caused by inactivating mutations in the PHEX gene. The other hereditary hypophosphatemic syndromes present a lower prevalence. These include autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets types 1 and 2 and the hereditary hypophosphatemic rickets with hypercalciuria. This article reviews the genetic basis of the different types of HHR, clinical manifestations, biochemical characteristics in blood and urine and new aspects of treatment.

Osteomalacia inducida por tumor: hemangiopericitoma rinosinusal / Tumor-induced osteomalacia: rhinosinusal hemangiopericytoma

La osteomalacia inducida por tumor es una rara enfermedad del metabolismo óseo caracterizada por el aumento en la excreción de fosfato a nivel renal seguido de hipofosfatemia. Es causada por agentes fosfatúricos producidos por determinados tumores. La resección total del tumor resulta en la completa reversión de las anormalidades bioquímicas, la desaparición de las manifestaciones clínicas y los hallazgos en los estudios por imágenes. Presentamos el caso de un varón de 61 años con cuadro clínico y laboratorio compatibles con osteomalacia oncogénica inducida por tumor mesenquimático de localización rinosinusal. En nuestro caso el diagnóstico histológico correspondió a una neoplasia de tipo vascular: hemangiopericitoma.

Tumor-induced osteomalacia is a rare disease of bone metabolism. The characteristic of this disease is an increase in phosphate excretion followed by hypophosphatemia, due to phosphaturic agents produced by different types of tumors. Tumor resection results in complete resolution of clinical, biochemical and radiological abnormalities. We present the case of a 61 year old man with signs, symptoms and laboratory findings consistent with oncogenic osteomalacia due to a rhino-sinusal mesenchymal tumor. The histological diagnosis showed a vascular neoplasm: hemangiopericytoma.