Background: Hereditary hypophosphatemic rickets with hypercalciuria(HHRH; OMIM: 241530) is a rare autosomal recessive disorder,which is the result of loss-of-function mutations in the sodium-phosphate-cotransporter NPT2c.This disorder is characterized by renal phosphate(Pi) wasting,hypercalciuria,increased 1,25 (OH)2-D levels and decreased parathormone(PTH) levels.Here we report the clinical features of two siblings with HHRH,confirmed with molecular diagnosis.
Case Reports: One of the two siblings born to first-degree-consanguineous parents, Case1 is a 16-year 9-month old boy, and Case 2 is a 8-year 8-month old girl. They were both referred to our outpatient-clinic due to bowing legs and difficulty in walking. In addition, Case 1 suffered fracture on his right femur, which was the fourth fracture on his leg. Birth histories and developmental-milestones were normal in both of them. At the referral time, weight, height and body mass index(BMI) of Case1 were 48 kg (-2.6 SDS),155.3 cm (-3.0 SDS) and 19.9 kg/m2 (-1.0 SDS) respectively,the puberty was Tanner 5. The anthropometric measurements of Case2 were 24.7 kg (-0.7 SDS), 129.9 cm (-0.1 SDS), 14.6 kg/m2 (-0.9 SDS) respectively, puberty was Tanner1 and genu valgus deformity was remarkable on physical examination. Laboratory examination of Case1 revealed serum calcium (Ca) 9.7 mg/dl, phosphorus (P) 1.7 mg/dl, alkaline-phosphatase (ALP) 360 U/L, 25 OH-D-vitamin 9.2 ng/ml, PTH 8.2 pg/ml (12- 65) and 1-25 D-vitamin 88 pg/ml (26-95).Bone mineral density at the spine (L1-L4) was measured as 0.697 g/cm2 (corrected z-score +0.7).Laboratory examination of Case2 revealed Ca 10.1 mg/dl, P 3.3 mg/dl, ALP 435 U/L, 25-OH-D vitamin 14.5 ng/ml and PTH 13.4 pg/ml. Tubular phosphate reabsorptions were 88% in both cases. Two siblings had also hypercalciuria and on follow-ups bilateral renal calculi in Case1 and bilateral Grade1 nephrocalcinosis in Case2 were detected. Metabolic tests and arterial blood gas test of cases were in normal ranges. In the light of these findings, HHRH was considered as pre-diagnosis and SLC34A3 gene analysis was performed. Genetic analysis revealed homozygous mutation in SLC34A3 c.756G>A (pGln252=) and c.1335+2T>A p.?(splice donor variant). After oral phosphorus treatment clinical and biochemical improvements were observed in both cases
Conclusion: Hereditary hypophosphatemic rickets with hypercalciuria is a rare cause of hypophosphatemic rickets.Diagnosis is important for the treatment.The clinical phenotype due to mutations in the SLC34A3 gene may vary even among effected siblings regarding to severity of hypophosphatemia,short stature,deformity in extremities and also frequency fractures.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology