Multidisciplinary approach for patients with nephropathic cystinosis: model for care in a rare and chronic renal disease / Abordagem multidisciplinar para pacientes com cistinose nefropática: modelo para atendimento em uma doença renal rara e crônica

Abstract Care for patients with chronic and rare diseases is complex, especially considering the lack of knowledge about the disease, which makes early and precise diagnosis difficult, as well as the need for specific tests, sometimes of high complexity and cost. Added to these factors are difficulties in obtaining adequate treatment when available, in raising patient and family awareness about the disease and treatment compliance. Nephropathic cystinosis is among these diseases. After more than 20 years as a care center for these patients, the authors propose a follow-up protocol, which has been used with improvement in the quality of care and consists of a multidisciplinary approach, including care provided by a physician, nurse, psychologist, nutritionist and social worker. In this paper, each field objectively exposes how to address points that involve the stages of diagnosis and its communication with the patient and their relatives or guardians, covering the particularities of the disease and the treatment, the impact on the lives of patients and families, the approach to psychological and social issues and guidelines on medications and diets. This protocol could be adapted to the follow-up of patients with other rare diseases, including those with renal involvement. This proposal is expected to reach the largest number of professionals involved in the follow-up of these patients, strengthening the bases for the creation of a national protocol, observing the particularities of each case.

Resumo A assistência a pacientes com doenças crônicas e raras é complexa, principalmente pela falta de disseminação de conhecimento sobre a doença, o que dificulta o diagnóstico preciso e precoce, além da necessidade da realização de exames específicos, por vezes de alta complexidade e custo. Somam-se a esses fatores dificuldades na obtenção de tratamento adequado quando disponível, na conscientização do paciente e da família sobre a doença e na aderência ao tratamento. A cistinose nefropática está entre essas doenças. Após mais de 20 anos como centro de atendimento a esses pacientes, os autores propõem um protocolo de seguimento, o qual vem sendo empregado com melhora na qualidade da assistência e consiste de uma abordagem multidisciplinar, incluindo, principalmente, atendimento prestado por médico, enfermeiro, psicólogo, nutricionista e assistente social. Neste artigo, cada área expõe de maneira objetiva como abordar pontos que envolvem as etapas do diagnóstico e sua comunicação ao paciente e a seus familiares ou responsáveis, abrangendo as particularidades da doença e do tratamento, o impacto na vida do paciente e de sua família, a abordagem das questões psicológicas e sociais e orientações quanto a medicamentos e dietas. Considera-se que este protocolo poderia ser adaptado ao seguimento de pacientes portadores de outras doenças raras, incluindo aquelas com envolvimento renal. Com essa proposta, espera-se alcançar o maior número de profissionais envolvidos no seguimento desses pacientes, fortalecendo as bases para a criação de um protocolo nacional, observando-se as particularidades de cada caso.

Síndrome de Fanconi y raquitismo hipofosfatémico asociado al uso de tenofovir en una niña infectada con VIH / Tenofovir-associated Fanconi`s syndrome and rickets in a HIV infected girl

El tenofovir (TDF) es un inhibidor de la transcriptasa reversa análogo de nucleótidos, aunque tiene buena tolerabilidad y alta actividad antirretroviral, su efecto sobre el riñón ha sido un motivo de preocupación. Objetivo: Describir el caso de una niña infectada por VIH que presenta síntomas y hallazgos de laboratorio compatibles con un síndrome de Fanconi durante el tratamiento con TDF como parte de su terapia antirretroviral. Caso clínico: Niña infectada por el VIH-1, que después de 18 meses con el tratamiento con TDF presentó pérdida de fuerza y dolor de las extremidades inferiores con deterioro funcional. Los hallazgos de laboratorio fueron compatibles con el síndrome de Fanconi. Las radiografías mostraron fractura bilateral de cadera y muñecas. El síndrome de Fanconi se recuperó por completo cuatro meses después del cambio de terapia antirretroviral. Conclusiones: Los médicos que prescriben TDF deben estar preparados para detectar signos y síntomas indicativos de disfunción renal y considerar de inmediato el cambio del fármaco a otro antirretroviral.

Tenofovir (TDF) is an inhibitor of reverse transcriptase nucleotide analogue, although it has good tolerability and high anti-retroviral activity, its effect on the kidney has been a concern. Objective: To describe a girl infected with HIV who presented Fanconi syndrome during antiretroviral therapy with TDF. Clinical case: We describe a HIV-1-infected girl, who after 18 months treatment with TDF presented loss of strength and pain of the lower extremities with functional impairment. Laboratory findings were consistent with Fanconi syndrome. Radiographs showed bilateral hip fracture and wrists. Full recovery of Fanconi syndrome was achieved four months after changing antiretroviral therapy. Conclusions: TDF-prescribing physicians must be prepared to detect signs and symptoms of renal dysfunction and immediately consider switching to another antiviral drug.

Fanconi-Bickel syndrome versus osteogenesis imperfeeta: An Iranian case with a novel mutation in glucose transporter 2 gene, and review of literature.

Fanconi-Bickel syndrome is an extremely rare hereditary metabolic disease, characterized by hepatomegaly due to glycogen storage, refractory hypophosphatemic rickets, marked growth retardation and proximal renal tubular acidosis. Recurrent bone fractures are one of the hallmark findings. It is a single gene disorder; the responsible gene belongs to the facilitative glucose transporters 2 (GLUT2) family gene or (SLC2A2) mapped to the q26.1-26.3 locus on chromosome 3, and encodes the GLUT protein 2. This protein is expressed in pancreatic ί-cells, hepatocytes, renal tubules, and intestinal mucosa. Several mutations in the GLUT2 gene have been reported in different ethnicities. Herein we report an Iranian girl with a missed diagnosis of osteogenesis imperfecta. She was referred with the history of frequent fractures, and severe motor delay and was suspected to osteogenesis imperfecta. Following the case we detected refractory rickets instead of OI, sever growth failure, proximal renal tubulopathy and RTA, and enlarged kidneys, progressive hepatomegaly, and GSD on liver biopsy. Glucose and galactose tolerance tests confirmed abnormal carbohydrate metabolism. Molecular analysis on GLUT2 gene revealed a homozygous novel mutation in exon 5; it was 15 nucleotide deletion and 7 nucleotide insertion and caused a frame shift mutation, produced a premature truncated protein (P.A229QFsX19). This mutation has not been reported before in the relevant literature.

Disfunción tubular renal distal en pacientes pediátricos con diagnóstico de desnutrición grave / Dystal renal tubular dysfunction in seriously undernourished pediatric patients

La acidosis metabólica es mas frecuente en los pacientes desnutridos graves que en los eutróficos. El objetivo del presente estudio fue evaluar la función tubular renal en 30 niños desnutridos graves hospitalizados. La investigación fue de tipo prospectiva, descriptiva de corte transversal, se realizó prueba de sobrecarga con bicarbonato de sodio al 5 por ciento a 30 desnutridos graves: marasmo, kwashiorkor o mixtos, con edades de 6 meses a 5 años, etiología primaria, de ambos sexos, hemodinámicamente estables, con acidosis metabólica, hipercloremia y anión gap urinario positivo. Se determinó la relación calcio/creatinina e índice ácido úrico/creatinina. Se calcularon las frecuencias absolutas, relativas, valores medios y desviación estándar. Los lactantes representaron 80 por ciento de los pacientes. Prevalecieron las formas clínicas kwashiorkor y mixtas de evolución crónica. En 12 (40,0 por ciento) pacientes se observó acidosis tubular renal distal. El valor promedio de la relación calcio/creatinina en menores de 2 años de edad fue de 0,362 ± 0,414 y en los mayores de 2 años de 0,265 ± 0,22. El valor promedio del índice ácido úrico/creatinina fue de 0,57 ± 0,28. La acidosis metabólica presente en los pacientes, de acuerdo a los resultados observados, obedece a una disfunción tubular renal distal. La interpretación de la relación calcio/creatinina e índice ácido úrico/creatinina urinaria resulta difícil, haciéndose necesario aumentar las investigaciones en estos pacientes.

Seriously undernourished patients have a bigger tendency to metabolic acidosis than euthrophic individuals. The objective of the present work was to realize a study of the renal tubular function in 30 severely undernourished children. The investigation was a prospective, descriptive and transversal study. A test of overload with 5 percent sodium bicarbonate was realized to 30 seriously undernourished children whose primari etiology was marasmus, kwashiorkor or with mixed conditions, with ages of 6 months to 5 years, from both sexes, hemodynamically stable, with metabolic acidosis, hiperchloremia and positive urinary anion gap. The relation calcium/creatinine and the index uric acid/creatinine were determined. The absolute and relatives frequencies, average values and standard deviations were calculated. Infants represented 80 percent of the evaluated patients. The clinical forms kwashiorkor and mixed forms, of chronic evolution prevailed. Distal tubular renal acidosis was observed in 12 patients (40 percent) after the test overload with 5 percent bicarbonate. The average values of the relation calcium/creatinine of children < 2 years was 0.362 ± 0.414 and of children > 2 years was 0.265 ± 0.222. The uric acid/creatinine index was 0.57 ± 0.28. Metabolic acidosis is frequent in serious infantile undernourishment, which, according to the results observed, obeys to distal renal tubular dysfunction. The interpretation of the relation calcium/creatinine and the uric acid/creatinine index is difficult, becoming necessary to increase the investigations in these patients.

Fanconi-Bickel syndrome.

We present here the first case of Fanconi-Bickel syndrome, a rare type of glycogen storage disease, from India. A 17-month-old female child presented with severe growth retardation and abdominal distention. Clinical examination revealed a "doll-like" face, massive hepatomegaly, and rickets. Laboratory investigations confirmed severe hypophosphatemic rickets and proximal renal tubular dysfunction. Liver biopsy showed glycogen accumulation in the hepatocytes.

A Case of IgA kappa Light Chain Deposition Disease and Combined Adult Fanconi Syndrome with Auer rod-like Intracytoplasmic Inclusions in Plasma Cells and Proximal Renal Tubular Cells / 대한진단검사의학회지

We report a case of IgA kappa light chain deposition disease and combined adult Fanconi syndrome with Auer rod-like intracytoplasmic inclusions in plasma cells and proximal renal tubular cells in a 54-yr-old female. Cytochemical stainings revealed a strong acid phosphatase activity of the inclusions and weak periodic acid-Schiff positivity, whereas the reactions for peroxidase and alpha-naphthyl acetate esterase were negative. An immunostaining verified IgA-kappa inside the plasma cells. Kidney biopsy revealed Bence Jones cast nephropathy with kappa light chain positivity, and Congo red staining was negative. Electron microscopy showed needle-shaped crystals located in tubular epithelial cells.

Distúrbios tubulares no período neonatal: quando suspeitar? / Renal tubular disorders in neonates: when they must be suspected?

Este artigo relata e discute os casos de dois recém-nascidos que apresentaram disfunções tubulares ainda no período neonatal. O primeiro diz respeito a um prematuro extremo, que apresentou sofrimento fetal agudo e necessitou de suporte ventilatório. Fez uso de antimicrobianos (ampicilina e gentamicina) para tratamento de quadro séptico e indometacina para fechamento farmacológico do canal arterial. Este neonato apresentou uma disfunção tubular generalizada, necessitando de uso crônico de bicarbonato oral. Essas alterações, no entanto, foram de caráter transitório, pois, atualmente, vêm evoluindo bem, tolerando redução progressiva da suplementação. O segundo caso se refere também a um prematuro extremo, mas que não apresentou complicações ao nascimento. Fez uso de ventilação mecânica por imaturidade pulmonar e antimicrobianos (vancomicina e ceftazidime) para tratamento de sepse neonatal. A partir da segunda semana de vida, observou-se acidose metabólica persistente associada a urina alcalina e poliúria com aumento da perda de cálcio e potássio, caracterizando uma acidose tubular renal distal clássica ou do tipo 1. Este paciente necessitou de doses elevadas de bicarbonato oral. Atualmente, ainda necessita de suplementação alcalina (8 mEq/ Kg/ dia), mas está com crescimento adequado e com as alterações metabólicas corrigidas. Estes casos ilustram a importância do diagnóstico precoce e tratamento dos distúrbios tubulares a fim de evitar desequilíbrios metabólicos graves, déficit de crescimento e dano renal definitivo.

This paper reports and discusses the cases of two neonates which presented tubular disorders during neonatal period. The first case describes an extremely premature newborn who suffered birth asphyxia and required mechanical ventilatory support. This newborn also used antibiotics (ampicillin and gentamicin) for the treatment of neonatal sepsis and indometacin for pharmacological closure of the patent ductus arteriosus. The neonate developed a global tubular dysfunction which demanded oral administration of sodium bicarbonate. However, these alterations seemed to be transient since this patient progressively reduced his need of bicarbonate supplementation. The second case refers to an extremely low-birth weight premature newborn who did not suffer birth asphyxia. This neonate also required mechanical ventilatory support for pulmonary immaturity and antibiotics (vancomycin and ceftazidime) for the treatment of neonatal sepsis. After the second week of life, it was observed a persistent metabolic acidosis associated with alkaline urine and polyuria with great loses of calcium and potassium. Taken together, these disturbances suggest the diagnosis of distal or type 1 renal tubular acidosis. Then, the newborn has needed progressive elevation of oral bicarbonate dosage. Actually, this patient receives oral bicarbonate (8 mEq/Kg/day) and, thus, has an appropriate growth, without metabolic alterations. These cases illustrate the importance of early recognition and treatment of renal tubular disorders in order to avoid homeostatic disarrangement, growth failure and permanent renal damage.

Cistinose nefropática: relato de 2 casos e revisäo da literatura / Nephropathic cystinosis: report of two cases and review of the literature

Os autores descrevem dois casos de cistinose nefropática, da forma infantil, que se apresentaram com síndrome de Fanconi e diabetes insipidus nefrogênico. Após a confirmaçäo diagnóstica através da identificaçäo de cristais de cistina pelo exame de lâmpada de fenda e aspirado de medula óssea, os pacientes receberam tratamento convencional de reposiçäo das perdas renais de eletrólitos e minerais. O paciente 1 evoluiu para óbito após quadro de broncopneumonia. No paciente 2 foi iniciado tratamento com cisteamina, que é eficaz na depleçäo de cistina dos tecidos, na dose média de 50 mg/kg/dia, sendo este o primeiro caso de terapêutica com cisteamina em nosso meio.