E-Poster Presentation 30th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2020

Vitamin D Deficient Rickets Type 1A: Case Report

Aviva Frydman¹

Vitamin D Deficient Rickets Type 1A: Case Report

Aviva Frydman¹, Jeffrey Zajac^2-3 , Christopher Yates¹

1. Department of Endocrinology, Western Health
2. Department of Endocrinology, Austin Health
3. Department of Medicine, University of Melbourne

We report the case of a 32-year-old female with vitamin D dependent rickets. She was diagnosed with congenital rickets at 18 months of age. Initial symptoms were inability to walk, bowed legs, failure to thrive and hypocalcaemic seizures. She was found to have low serum calcium, low phosphate, elevated parathyroid hormone (PTH), elevated alkaline phosphatase (ALP), normal 25 hydroxyvitamin D (25OHD), and very low 1,25 dihydroxyvitamin D (1,25(OH)₂D). X-rays revealed gross rachitic changes in the skeleton, hands and knees at 21 months. She was treated with oral calcitriol, but had recurrent hypocalcaemia requiring intravenous calcium. By age 12, X-rays revealed anterior bowing of bilateral mid to lower tibiae and lateral bowing of bilateral femora. At age 22 an iliac crest biopsy revealed marked reduction in mineralized bone consistent with severe osteomalacia/rickets with scattered healing microfractures. Throughout her 20s she remained intermittently adherent to oral calcitriol and calcium supplementation. Her rickets has been complicated by a right femoral diaphyseal fracture, bilateral femoral osteotomies for severe bowing and she requires a scooter for mobilization. She has had two successful pregnancies.

She is one of eight children of non-consanguiness parents. Two brothers were diagnosed with rickets 6-7 months of age (figure 1). Family genetic testing in 2016 revealed a CYP27B1 gene mutation in one allele. She may be a compound heterozygote for CYP27B1 mutations, however no mutations have been identified in the other allele to date.

There are 3 main forms of Vitamin D Dependent Rickets (VDDR) (1). VDDR type 1A is an autosomal recessive condition resulting from biallelic mutations in the CYP27B1 gene which codes for 1a hydroxylase, the enzyme responsible for conversion of 25OHD to 1,25(OH)₂D. Impaired hydroxylation leads to normal or high levels of 25OHD but low levels of 1,25(OH)₂D, consistent with our case. Treatment requires oral replacement of calcitriol.

, Jeffrey Zajac² , Christopher Yates¹

1. Department of Endocrinology, Western Health
2. Department of Endocrinology, Austin Health

We report the case of a 32-year-old female with vitamin D dependent rickets. She was diagnosed with congenital rickets at 18 months of age. Initial symptoms were inability to walk, bowed legs, failure to thrive and hypocalcaemic seizures. She was found to have low serum calcium, low phosphate, elevated parathyroid hormone (PTH), elevated alkaline phosphatase (ALP), normal 25 hydroxyvitamin D (25OHD), and very low 1,25 dihydroxyvitamin D (1,25(OH)₂D). X-rays revealed gross rachitic changes in the skeleton, hands and knees at 21 months. She was treated with oral calcitriol, but had recurrent hypocalcaemia requiring intravenous calcium. By age 12, X-rays revealed anterior bowing of bilateral mid to lower tibiae and lateral bowing of bilateral femora. At age 22 an iliac crest biopsy revealed marked reduction in mineralized bone consistent with severe osteomalacia/rickets with scattered healing microfractures. Throughout her 20s she remained intermittently adherent to oral calcitriol and calcium supplementation. Her rickets has been complicated by a right femoral diaphyseal fracture, bilateral femoral osteotomies for severe bowing and she requires a scooter for mobilization. She has had two successful pregnancies.

She is one of eight children of non-consanguiness parents. Two brothers were diagnosed with rickets 6-7 months of age (figure 1). Family genetic testing in 2016 revealed a CYP27B1 gene mutation in one allele. She may be a compound heterozygote for CYP27B1 mutations, however no mutations have been identified in the other allele to date.

There are 3 main forms of Vitamin D Dependent Rickets (VDDR). VDDR type 1A is an autosomal recessive condition resulting from biallelic mutations in the CYP27B1 gene which codes for 1a hydroxylase, the enzyme responsible for conversion of 25OHD to 1,25(OH)₂D (figure 1). Impaired hydroxylation leads to normal or high levels of 25OHD but low levels of 1,25(OH)₂D, consistent with our case. Treatment requires oral replacement of calcitriol.

Images and tables

Figure 1: Vitamin D metabolism