ESPE Abstracts

Background & Aim: Vitamin D-dependent rickets type 1 A (VDDR1A) is an autosomal recessive condition caused by mutation in CYP27B1, which encodes 1 α-hydroxylase enzyme that catalyzes the conversion of 25-hydroxyvitamin D (25OHD) to 1,25-dihydroxyvitamin D (1,25 (OH)₂D). We are reporting 4 cases of VDDR1A due to CYP27B1 mutation initially misdiagnosed as vitamin D deficient and hypophosphatemic rickets.

Case Summaries: We identified 4 cases (all male) from 3 different families of VDDR1A due to homozygous CYP27B1 mutation (c.1319_1325dup p.(Phe443Profs*24)) over 1 year. All were born to consanguineous parents with one case had a history of 4 siblings’ death. Initial presentation was bony deformities and failure to thrive in late infancy (9- 12 months). Three had additional complaints of abdominal distension with repeated diarrheas and one had a history of fracture after minor trauma. All were initially misdiagnosed as vitamin D deficient rickets and hypophosphatemic rickets (treated with cholecalciferol and joule’s solution) and referred to tertiary care at mean age of 2.8 (1.5-3.9) year because of failure to respond to treatment. At presentation mean height was at -4.10 (-2.10 to -4.88) SD and BMI was at -0.18 (1.96 to -1.84) SD. All cases had signs of frank rickets and three had abdominal distension with hepatomegaly. Bone profile revealed low-normal calcium (7.9-8.9 mg/dl), low phosphate (1.5-2.2 mg/dl), normal magnesium (2-2.5mg/dl), raised Alkaline phosphatase (868 – 3723 IU/l), normal to raised 25-OHD level (39.8-122 ng/ml) and raised PTH (80.9- 771 pg/ml). Fractional excretion of phosphate was > 15% (17%-23%) and tubular reabsorption of phosphate was <85% (76-84%). 1,25 (OH)₂D were not done due to non-availability. Skeletal survey showed florid rickets with marked osteopenia. After genetic confirmation of VDDR1A due to CYP27B, joule solution was stopped, and alfacalcidol was started at the dose of 150 ng/kg/day along with calcium supplementation. Two months post-treatment follow up showed they are catching up with mean height velocity 7.7 (4.06-12.3) cm/year, normalization of calcium and phosphorus, decreasing trend of alkaline phosphatase and PTH, normal urine calcium to creatinine ratio and x-ray showing interval improvement with zone of healing.

Conclusion: VDDR1A is often missed and presented late in resource limited countries due to lack of availability of 1,25 (OH)₂D level and genetic testing. It is easily treatable condition with excellent outcome if diagnosed timely and managed promptly.