Adult Idiopathic Renal Fanconi Syndrome: A Case Report

Renal Fanconi syndrome (RFS) is caused by generalized proximal tubular dysfunction and can be divided into hereditary and acquired form. Adult-onset RFS is usually associated with drug toxicity or systemic disorders, and modern molecular genetics may explain the etiology of previous idiopathic cases of RFS. Here, we report the case of a 52-year-old woman with RFS whose etiology could not be identified. She presented with features of phosphaturia, renal glucosuria, aminoaciduria, tubular proteinuria, and proximal renal tubular acidosis. Her family history was unremarkable, and previous medications were nonspecific. Her bone mineral density was compatible with osteoporosis, serum intact parathyroid hormone level was mildly elevated, and 25(OH) vitamin D level was insufficient. Her blood urea nitrogen and serum creatinine levels were 8.4 and 1.19 mg/dL, respectively (estimated glomerular filtration rate, 53 mL/min/1.73 m²). Percutaneous renal biopsy was performed but revealed no specific renal pathology, including mitochondrial morphology. No mutation was detected in EHHADH gene. We propose the possibility of involvement of other genes or molecules in this case of adult RFS.

Adefovir-induced Fanconi syndrome associated with osteomalacia

Fanconi syndrome is a dysfunction of the proximal renal tubules that results in impaired reabsorption and increased urinary loss of phosphate and other solutes. The pathophysiology of drug-induced Fanconi syndrome is unclear. Here we report the case of a 36-year-old woman who presented with pain in multiple bones and proteinuria. She had a 7-year history of taking adefovir at 10 mg/day for chronic hepatitis B. Three years previously she had received surgery for a nontraumatic right femur neck fracture, after which she continued to complain of pain in multiple bones, and proteinuria, glycosuria, and phosphaturia were noted. The findings of a light-microscope examination of a renal biopsy sample were normal, but mitochondrial damage of the proximal tubules was evident in electron microscopy. Western blot analysis revealed that the level of serum fibroblast growth factor 23 (FGF23) was lower than in normal controls. After 2 months of treatment, hypophosphatemia and proximal tubular dysfunction were reversed, and serum FGF23 had normalized. This case suggests that direct mitochondrial damage in proximal tubules can cause drug-induced Fanconi syndrome associated with osteomalacia.

Case report of tumour-induced osteomalacia with parotid gland tumour as a focus / Journal of the ASEAN Federation of Endocrine Societies

@#<p style="text-align: justify;">Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, which is characterized by overproduction of FGF23 as a phosphaturic agent leading to chronic phosphaturia and hypophosphatemia, associated with inappropriately normal or low levels of vitamin D. We describe a rare case of a 57-year-old Indian female who presented with bone pains, muscle pains and lower limb weakness. On examination she was found to have hypophosphatemia. Our work up led to the identification of a FGF23 secreting parotid tumour. The tumour responsible for symptoms was a pleomorphic adenoma of the parotid gland. Its complete resection resulted in normalisation of patient's symptoms. Laboratory parameters and microsopic examination further revealed a mesenchymal tumour of mixed connective tissue type.</p>

Raquitismo e osteomalácia hipofosfatêmicos de origem genética mediados por FGF23: caracterização molecular, óssea e renal / FGF23-mediated inherited hypophosphatemic rickets: molecular characterization, bone analysis and renal evaluation

Introdução: raquitismo e osteomalácia hipofosfatêmicos de origem genética mediados por FGF23 (RQ/OM-FGF23) são caracterizados pelo aumento patológico dos níveis séricos de FGF23 com consequentes hiperfosfatúria e hipofosfatemia. A forma hereditária mais comum é a ligada ao X dominante (XLHR) ocasionada por mutações inativadoras no gene PHEX. Objetivos: identificar a etiologia molecular; avaliar a densidade mineral óssea (DMO) e a microarquitetura óssea e, determinar a prevalência de nefrocalcinose (NC), nefrolitíase (NL) e de alterações metabólicas urinárias em 47 pacientes com RQ/OM-FGF23 (16 crianças e 31 adultos). Métodos: as análises dos genes PHEX e FGF23 foram realizadas pelos métodos de Sanger e MLPA. A DMO areal (DMOa) foi avaliada por densitometria óssea (DXA), enquanto a DMO volumétrica (DMOv) e os parâmetros de microarquitetura óssea foram analisados por HR-pQCT. A NC foi classificada segundo uma escala de 0-3 (0 = ausência de NC; 3 = NC grave) pelas ultrassonografia (US) e tomografia computadorizada (TC) renais. A presença de NL foi analisada pela TC renal. Fatores de risco para NC e NL foram avaliados pela urina de 24 horas. Resultados: foram identificadas mutações no PHEX em 41 pacientes (87,2%). A avaliação óssea foi realizada em 38 pacientes com XLHR que foram comparados a controles saudáveis. Os pacientes tiveram maior DMOa em L1-L4 (p=0,03) e menor DMOa em 1/3 distal do rádio (p < 0,01). Em rádio distal, a DMOv total (Total.vBMD) e os componentes trabecular (Tb.vBMD) e cortical (Ct.vBMD) foram semelhantes entre os grupos. Na tíbia distal, os pacientes apresentaram menor Total.vBMD em relação aos controles devido ao déficit no Tb.vBMD (p < 0,01). Além do mais, ao separarmos por status metabólico, os pacientes descompensados tiveram menor Ct.vBMD em tíbia distal comparados aos controles (p=0,02). Quanto aos parâmetros estruturais, em rádio distal, os pacientes apresentaram menor número de trabéculas (Tb.N; p=0,01), maior espessura trabecular...

Background: FGF23-mediated hypophosphatemic rickets is a group of diseases characterized by a pathological increase of FGF23 serum levels, resulting in hyperphosphaturia and hypophosphatemia. In this group, the most common form of inheritance is the X-linked dominant (XLHR) caused by inactivating mutations in the PHEX gene. Aims: to identify the molecular basis; to evaluate the bone mineral density and bone microarchitecture; to determinate the prevalence of nephrocalcinosis (NC), nephrolithiasis (NL) and their related metabolic factors in 47 patients with FGF23-mediated hypophosphatemic rickets (16 children and 31 adults). Methods: PHEX and FGF23 were analyzed by conventional Sanger sequencing and MLPA. The areal BMD (aBMD) was evaluated by dual-energy x-ray absorptiometry (DXA), while the volumetric BMD (vBMD) and the bone microarchitecture were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT). NC was investigated by renal ultrasonography (US) and computed tomography (CT) and classified using a 0-3 scale (0= no NC and 3= severe NC). The presence of NL was determined by renal CT. Risk factors for NC and NL were evaluated by 24-hour urinary samples. Results: 41 patients (87.2%) presented mutations in PHEX. The bone analysis was made in 38 XLHR patients compared to healthy controls. XLHR patients presented higher aBMD at L1-L4 (p=0.03) and lower aBMD at the distal third of the radius (p < 0.01). At the distal radius, HR-pQCT showed no differences in the vBMD neither in its trabecular (Tb.vBMD) and cortical (Ct.vBMD) components. At the distal tibia, the XLHR patients showed lower Total.vBMD (p < 0.01) compared to controls due to decreased Tb.vBMD (p < 0.01). Moreover, after XLHR patients were sorted by metabolic status, the noncompensated ones revealed lower Ct.vBMD at the distal tibia compared to their respective controls (p=0.02). Regarding to the microarchitectural parameters, at the distal radius, XLHR...

A Case of Tubulointerstitial Nephritis and Uveitis with Fanconi Syndrome / 대한내과학회지

Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease that comprises 4.7% of acute interstitial nephritis. With reno-ocular manifestations, TINU syndrome is accompanied by symptoms such as fever, fatigue, malaise, anorexia, vomiting, and arthralgia. TINU syndrome is reported mainly in children or adolescent girls, and it is rare in adults. Although TINU syndrome can present with multiple renal tubular defects, Fanconi syndrome characterized by generalized impairment of proximal tubular function, leading to renal glucosuria, hyperuricosuria, hyperphosphaturia, proximal renal tubular acidosis, and kaliuresis leading to hypokalemia, has rarely been described. We report a case of TINU syndrome with Fanconi syndrome in a 46-year-old HLA B27-positive Korean woman.

Three Cases of Osteomalacia with Fractures Induced by Adefovir in Chronic Hepatitis B / 대한골다공증학회지

Adefovir dipivoxil is used antiviral agent in the treatment of chronic hepatitis B virus infection. This drug is recommended for patients infected with lamivudine-refractory hepatitis B. Many studies of low-dose adefovir have shown little evidence of renal tubular dysfunction. However, hypophosphatemic osteomalacia has recently been reported in patients treated with adefovir. We report three cases of low dose adefovir-induced hypophosphatemic osteomalacia with fractures. All three patients had been receiving adefovir due to lamivudine-refractory hepatitis B, presented multiple bone pain. The laboratory tests revealed hypophosphatemia and phosphaturia. Bone scintigraphy showed increased uptake in multiple lesions. They were diagnosed as adefovir induced hypophophatemic osteomalacia. Changing the antiviral agent and administration of calcitriol and phosphates improved hypophosphatemia and clinical symptoms. Patients with hepatitis B virus treated with adefovir should be monitored with the serum phosphate levels and presenting symptoms of diffuse bone pain, clinicians need to suspect this infrequent complication.

Osteomalacia por tumor secretor de FGF-23 / Ostemalacia due to a tumor secreting FGF-23

Se presenta un caso de osteomalacia oncogénica en un varón de 50 años, con fuertes dolores óseos y gran debilidad muscular durante 4 años. Tenía varias deformidades vertebrales dorsales en cuña, fracturas en ambas ramas iliopubianas y en una rama isquiopubiana, y una zona de Looser en la meseta tibial derecha. Se localizó un tumor de 2 cm de diámetro en el hueco poplíteo derecho mediante centellograma con octreótido marcado con tecnecio. El tumor fue extirpado quirúrgicamente. La microscopía mostró un tumor mesenquimático fosfatúrico, de tejido conectivo mixto. La inmunotinción demostró FGF-23. Hubo rápida mejoría, con consolidación de las fracturas pelvianas y de la pseudofractura tibial y normalización de las alteraciones bioquímicas.

A case of oncogenic osteomalacia in a 50-year-old male is here presented. He suffered severe bone pain and marked muscular weakness of 4 years' duration. There were several vertebral deformities in the thoracic spine, bilateral fractures of the iliopubic branches, another fracture in the left ischiopubic branch, and a Looser's zone in the right proximal tibia. An octreotide-Tc scan allowed to identify a small tumor in the posterior aspect of the right knee. It was surgically removed. Microscopically, it was a phosphaturic mesenchymal tumor-mixed connective tissue (PMT-MCT). Expression of FGF-23 was documented by immune-peroxidase staining. There was rapid improvement, with consolidation of the pelvic fractures and the tibial pseudo-fracture. The laboratory values returned to normal.

Phosphaturia as a Promising Predictor of Recurrent Stone Formation in Patients with Urolithiasis

PURPOSE: Recent studies have suggested that renal phosphate leakage and the associated phosphaturia are significant underlying causes of calcium urolithiasis. The aims of this study were to assess whether phosphaturia relates to urinary metabolic abnormalities and recurrent stone formation. MATERIALS AND METHODS: A database of patient histories and urine chemistries was analyzed for 1,068 consecutive stone formers (SFs) and 106 normal controls. Urine values for phosphaturia that were higher than 95% of the normal control values were defined as indicating hyperphosphaturia, and the effect of phosphaturia on urinary metabolites and stone recurrence was determined. Of these patients, 247 patients (23.1%) who had been followed up for more than 36 months or had a recurrence of stones during follow-up (median, 46.0 months; range, 5-151) were included in the analyses for stone recurrence. RESULTS: Of the SFs, 19.9% (212/1,068) had increased urinary phosphate excretion. SFs with hyperphosphaturia had a greater urinary volume and higher levels of calcium, uric acid, oxalate, and citrate than did SFs with normophosphaturia. A multivariate Cox regression model, stratified by stone episodes, revealed that hyperphosphaturia was an independent predictor of recurrent stone formation in first-time SFs (hazard ratio [HR]: 2.122; 95% confidence interval [CI]: 1.100-4.097; p=0.025). No association was detected between hyperphosphaturia and recurrent stone formation in recurrent SFs. Kaplan-Meier curves showed identical results. CONCLUSIONS: This study demonstrates that hyperphosphaturia is closely associated with urinary metabolic abnormalities. Furthermore, hyperphosphaturia is a significant risk factor for stone recurrence in first-time SFs.

Contribución de la vigilancia del crecimiento a la calidad de atención: un modelo de gestión / Contribution to the monitoring of growth and quality of patient care: a management model

El estudio del crecimiento a largo plazo de niños con raquitismo hipofosfatémico familiar, demostró que 18 de los 30 pacientes estudiados no crecían adecuadamente, y que a su vez este pobre crecimiento estaba asociado a una falta de cumplimiento de la ingesta de fósforo indicada por el médico tratante, medicación que forma parte esencial de la terapia. Entre las principales causas identificadas de falta de cumplimiento se encontró la incapacidad de muchas farmacias del país de preparar la solución de sales de fósforo, las dificultades de transporte y conservación de dichas sales, la inestabilidad de la solución, la falta de recursos de los pacientes sin cobertura, la dificultad de las obras sociales en financiar las sales en los pacientes con cobertura. Luego de reuniones mantenidas entre miembros de un equipo multidiciplinarios formado ad hoc, la farmacia del hospital logró preparar una cápsula con sales de fósforo para ser disuelta en agua en el hogar, se estableció un circuito de entrega gratuita del medicamento al paciente aprobado por las autoridades del Hospital, y un sistema de cobro a los organismos pagadores en los casos que correspondiera. La autorización de la Dirección fue tomada en base a la necesidad de mejorar la calidad de atención en estos pacientes, al relativo bajo costo del medicamento (1180 pesos por pacientes por año), y el escaso número de pacientes bajo tratamiento. La vigilancia del crecimiento en pacientes crónicos probó en este caso ser una herramienta confiable y sencilla para detectar un problema generalizado en el tratamiento de una enfermedad y mejorar la calidad de la atención.

Crecimiento a largo plazo de pacientes con raquitismo hipofosfatémico familiar (RHF) / Long term growth in patients with familial hypophosphatemic rikets

El raquitismo hipofosfatémico familiar (RHF) es una condición genética trasmitida en la mayoría de los casos en forma dominante ligada al sexo, que se asocia a un pérdida renal de fosfatos, con secundaria hipofosfatemia, déficit de osificación, incurvación de miembros inferiores y retraso de crecimiento. Objetivo: describir el crecimiento y su relación con el cumplimiento del tratamiento a largo plazo, en un grupo de pacientes seguidos en el Hospital Garrahan por los servicios de Crecimiento y Desarrollo, Nefrología y Endocrinología. Tiempo de observación de 1.0 a 16.4 años. Población y Métodos: N= 30 pacientes (18 mujeres y 13 varones). Se midió la estatura según técnica estandarizada y se trataron los pacientes en forma uniforme con sales de fósforo 1-25 (HO2) vitamina. Se definió incumplimiento del tratamiento como la discontinuidad de la ingesta de sales de fósforo de más de un mes por año. Resultados: La edad mediana de inicio de tratamiento fue 4.92 años (r: 0.7/12.7), talla media: -2.85 Ds (r. -42/6.7) y a la última consulta: 15.04 años (r: 4.66/20.73), talla media: -3.31 Ds (r: -0.70/-6.6). En promedio, los niños crecieron entre 2.8/3.0 DS. Hubo 12 niños que perdieron estatura durante el seguimiento. La mayor proporción del déficit de talla ya estaba presente al diagnóstico. La regresión logística entre pérdida de talla en puntajes z (0.5 DS o más), y cuatro variables independientes (edad al diagnóstico), cumplimiento del tratamiento, sexo y talla al diagnóstico, cumplimiento al tratamiento, sexo y talla al diagnóstico) reveló que sólo las dos primeras están significativamente relacionadas al déficit de crecimiento (P 0.02 y 0.03 respectivamente). Conclusión: la edad tardía al diagnóstico y el incumplimiento del tratamiento se asocian a déficit de crecimiento.

A Case of Multiple Myeloma with Ameliorated Bone Pain after Treatment of Adult Fanconi Syndrome / 대한신장학회지

Adult Fanconi syndrome is characterized by variable abnormalities caused by renal proximal transport defects, resulting in glycosuria, aminoaciduria, bicarbonaturia, uricosuria and phosphaturia. A 57-year-old man with kappa-light chain multiple myeloma, undergoing chemotherapy with prednisolone and melphalan for 17 month, was admitted with spontaneous femoral neck fracture and was consulted due to polyuria and refractory metabolic acidosis immediately after hemiarthroplasty. The laboratory values showed normal anion gap metabolic acidosis with normal urinary anion gap, hypokalemia, hypouricemia, hypophosphatemia at the time of consultation. After partial correction of acidemia, the fractional excretion of HCO3- was 11.9%, it was interpreted as proximal renal tubular acidosis. 24-hour urine collection showed increased level of excretion for most aminoacids. Diffuse osteopenia and multiple compression fractures on spine were detected on radiological examinations. Also, osteoporosis and osteomalacia was suggested during his clinical course. After the diagnosis of Fanconi syndrome was made, treatment was started with sodium bicarbonate, potassium citrate, calcitriol, calcium carbonate along with phosphate rich diet. Laboratory abnormalities were corrected and refractory multiple bone pain was ameliorated with these treatment.

Two Cases of Oculocerebrorenal Syndrome in Two Brothers Diagnosed after Congenital Cataract Surgery

PURPOSE: We report two cases of brothers diagnosed with oculocerebrorenal syndrome after binocular congenital cataract surgery. METHODS: Two brothers who had undergone surgeries for congenital cataracts showed growth retardation, proteinuria, and generalized tonic seizures. The patients were referred to the pediatrics department and evaluated for systemic diseases and genetic counseling. RESULTS: Two brothers had renal tubular dysfunction characterized by hypercalciuria and hyperphosphaturia. The older brother had multiple microcalcifications on both kidneys, and ischemic injury with general dysfunction of the brain. Genetic analysis of brothers and their mother showed a new mutation of P799L in the region of the chromosome Xq25-26.1 locus. The two brothers were diagnosed with oculocerebrorenal syndrome of Lowe (OCRL). CONCLUSIONS: In cases of patients with congenital cataracts, the evaluation of systemic disease including genetic abnormality should be considered whenever systemic symptoms such as growth retardation, proteinuria or seizure are found.

Non-azotemic refractory rickets in Indian children.

In order to examine the etiology of refractory rickets, we evaluated the case records of patients presenting between 1990 and 2002. Subjects with impaired renal functions were excluded. Of 131 patients, 25.9 % each had hypophosphatemic rickets and distal renal tubular acidosis (RTA), 19.6 %vitamin D dependent rickets (VDDR), 11.3 % proximal RTA, 9.1 % liver disease and 6.1 % malabsorption. A significant proportion of patients with VDDR and proximal RTA showed deformities in the first year of life, whereas those with distal RTA and hypophosphatemic rickets presented later. Patients with hypophosphatemic rickets had predominant involvement of lower limbs; hypercalciuria was found in 4. Distal RTA was associated with marked rickets and normal levels of alkaline phosphatase. Hypophosphatemia and low tubular reabsorption of phosphate, though characteristic of hypophosphatemic rickets, was also seen in patients with VDDR (19.2%) and distal RTA (17.6 %). Our findings suggest that application and interpretation of appropriate investigations are useful in determining the cause of non-azotemic refractory rickets allowing initiation of specific therapy.

Clinical Characteristics of Arthrogryposis, Renal Tubular Dysfunction, Cholestasis(ARC) Syndrome in Korea

PURPOSE: ARC syndrome refers to an association of arthrogryposis, renal tubular dysfunction, and cholestasis. The VPS33B gene was recently identified as the causative gene. So far, 41 cases of ARC syndrome have been reported worldwide, and it has rarely been reported in Korea. This study was conducted to report the clinical findings of seven ARC syndrome cases in Korean children, focusing especially on renal tubular dysfunction. METHODS: The hospital records of 7 cases diagnosed as ARC syndrome at Severance Hospital between Mar. 1995 and Aug. 2005 were reviewed and analyzed. RESULTS: Of the 7 cases, 4 were boys and 3 were girls. Six patients(85%) were born with normal birth weight at term, and one was born at preterm. All cases presented with cholestasis and severe jaundice. According to the type of arthrogryposis described by Brown et al, type 3 and 4 were found in 2 patients and type 6, 7, and the undistributed type in one patient respectively. Other associated clinical findings were as follows:failure to thrive in 6(85%), lax skin in 5(71%), and gray platelet syndrome in 4(57%). Urine analysis revealed 6 cases(85%) with proteinuria, 3(43%) with hematuria, 5(71%) with glycosuria, 2(29%) with phosphaturia and 2(29%) with calciuria. Serum electrolytes showed 4 cases(57%) with hyponatremia, 3(43%) with hypokalemia, and 1(14%) with creatinine elevation. Renal tubular dysfunctions were diagnosed as renal tubular acidosis in 6 cases(85%), nephrogenic diabetes insipidus in 2(29%), and Fanconi syndrome in 2(29%). During the follow-up period, 2(29%) had no treatment, 5(85%) had continuous supplementation to correct the electrolyte imbalance and acidosis, and 1(14%) had dialysis. Only one patient had a family history of ARC syndrome in a sibling. Four cases(57%) were diagnosed at the mean age of 8.2 months, and one case was lost during follow-up. Ages of the survived 2 cases were 13 and 25 months, respectively. CONCLUSION: The rare disease of ARC syndrome is associated with severe renal dysfunction. However, this study revealed that the renal manifestation of ARC syndrome in Korean children is relatively mild and survival rate is higher than that of previous studies. Contrary to previous reports, this study showed that familial cases are rare and sporadic occurence is possible in Korea. Thus, the diagnosis of this syndrome requires a careful evaluation of the renal function in cases of congenital arthrogryposis, and a mandatory genetic counseling of affected family for prevention of familial occurance.

Distintas formas de presentación clínica de un raquitismo hipofosfatémico autosómico dominante por mutación del factor de crecimiento fibroblástico 23 en una familia / Different forms of clinical presentation of an autosomal dominant hypophosphatemic rickets caused by a FGF23 mutation in one family

In this report we describe different forms of clinical presentation of an autosomal dominant hypophosphatemic rickets (ADHR) in 4 members of the same family as well as the treatment used in these patients and their response to it. Patient No 1: a 60 year old female who consulted for bone pain: Bone densitometry showed osteoporosis. Laboratory assays showed hypophosphatemia with low renal phosphate threshold, high total alkaline phosphatase, normal intact PTH and normal serum calcium. With neutral phosphate and calcitriol, the biochemical parameters normalized and bone densitometry improved significantly in less than a year. Patient No 2 her grand daughter consulted at 1 year and 8 months of age for growth retardation (height at percentile 3) and genu varum. Laboratory assays showed low serum phosphate and high total alkaline phosphatase; thickening and irregular epiphyseal borders of the wrists were observed radiologically. She began treatment with calcitriol and phosphorus with normalization of laboratory parameters and increase in growth (height increasing to percentile 50 after 20 months of therapy). Patient No 3: mother of patient No 2, she had no clinical manifestations and normal densitometry but presented low serum phosphate (1.9 mg/dl) that normalized with neutral phosphate therapy. Patient No 4: he was the youngest son of Patient No 1, who had had hypophosphatemic rickets, by age 5; his serum phosphate normalized without treatment At age 29, he presented normal serum phosphate and bone densitometry. Genomic DNA analysis performed in patient No 3, showed missense mutation with substitution of arginine at position 179 for glutamine. The family was catalogued as having autosomal dominant hypophosphatemic rickets/osteomalacia.

Describimos distintas formas de presentación clínica de un raquitismo hipofosfatémico autosómicodominante en 4 miembros de una misma familia y su respuesta al tratamiento. Paciente N° 1: de sexofemenino de 60 años que consultó por dolores costales y pélvicos, con osteoporosis densitométrica, hipofosfatemia con bajo umbral renal de fósforo, PTH intacta normal y calcemia normal. Tratada con fósforo neutro y calcitriol logró la normalización bioquímica y una notable mejoría de la densitometría en menos de un año. Paciente N° 2: su nieta, consultó al año y ocho meses de edad por presentar talla en percentil 3 y genu varum. En el laboratorio mostró hipofosfatemia y fosfatasa alcalina total muy elevada y en la Rx de mano, ensanchamiento y deflecamiento epifisario compatible con raquitismo. Tratada con fósforo neutro y calcitriol, normalizó los parámetros bioquímicos y logró un ascenso en el percentil de talla de 3 a 50 a los 20 meses de tratamiento. Paciente N° 3: la madre de la paciente N° 2, quien sin ninguna manifestación clínica y con densitometría ósea normal presentó hipofosfatemia que se normalizócon tratamiento con fosfato neutro. Paciente N° 4: el tío de la paciente N° 2, tuvo raquitismo hipofosfatémico de niño,y luego de los 5 años normalizó el fósforo sin tratamiento. Estudiado a los 29 años presentó fósforo normal y densitometría ósea normal. El análisis del ADN genómico de la paciente N° 3 mostró una mutación con sentido erróneo en el gen del factor de crecimiento fifroblástico 23 (sustitución de arginina por una glutamina en posición 179). Por lo tanto se llegó al diagnóstico de raquitismo/osteomalacia hipofosfatémico autosómico dominante.

Clinical Study of Hypophosphatemic Rickets

PURPOSE: Hypophosphatemic rickets is a hereditary disease, characterized by hypophosphatemia due to renal phosphate wasting, impaired renal production of 1,25-dihydroxyvitamin D3, rachitic bone deformities and impaired growth. The purpose of this study is to provide clinical profiles of patients with hypophosphatemic rickets in our hospital. METHODS: Between July 1983 and February 2004, 56 patients were diagnosed as having hypophosphatemic rickets. The medical records of these patients were reviewed retrospectively. Clinical manifestations, family histories, laboratory data, treatment outcomes were described. RESULTS: Fifty six patients were enrolled in this study. The average age at symptom onset and diagnosis were 20 months and 5 years respectively. Fourteen patients had family histories. The main clinical manifestations were bow legs and short stature. There was a significant negative correlation between the ages and the height z-scores at the time of diagnosis(r=-0.47, P=0.005). Initial laboratory data showed normocalcemia, hypophosphatemia, elevated serum alkaline phosphatase, decreased tubular reabsorption of phosphate and a normal range of 1,25-dihydroxyvitamin D3. Radiographic examinations of bone revealed fraying, widening and cupping of the metaphyseal ends. Treatment consisted of Joulie solution and vitamin D metabolites, and resulted in improved biochemical and radiographic findings. However, height z-scores remained essentially unchanged(P=0.224). Complications of treatment were frequently observed, including hyperparathyroidism, nephrocalcinosis, and hypercalciuria. Sixteen patients had corrective osteotomy and 4 of them underwent leg lengthening together. CONCLUSION: There was a gap of several years between the onset of symptoms and the diagnosis. Early treatment seems to be essential to growth. For the earlier treatment, the offsprings of affected parents should be followed up closely.