Vitamin D-dependent rickets (VDDR) type 1: case series of two siblings with a CYP27B1 mutation and review of the literature

Abstract

Two siblings presented with clinical and biochemical features of rickets, initially suspected as hypophosphatemic rickets. There was no improvement initially, hence the siblings were reinvestigated and later diagnosed as having vitamin D-dependent rickets (VDDR) type 1 due to a rare mutation in the CYP27B1 gene encoding the 1α-hydroxylase enzyme. Both siblings improved with calcitriol supplementation. The initial presentation of VDDR is often confusing and algorithmic evaluation helps in diagnosis. We also present a brief review of the literature, including genetics.

Lifelong deformities in an adult caused by vitamin D‑dependent rickets type 1A: A case report

“…This suggests that Chinese patients with VDDR-1A are predominantly heterozygous for this mutation. A previous report in 2020( 14 ) described two brothers from India with VDDR-1A diagnosed at 30 and 15 months, respectively. They presented with complaints of slow growth, inability to stand, hypotonia and rickets, where genetic testing revealed a homozygous c.1294C>T (p.R432C) mutation.…”

“…The patient's genetic sequencing results were consistent missense mutations. Partial mutations in the CYP27B1 gene, such as Q65H, R107H and P112L, can cause loss of enzyme activity, resulting in severe phenotypes ( 14 ). Other mutations, such as G57V, G73W and R459C, are associated with moderate to severe phenotypes ( 14 ).…”

“…Partial mutations in the CYP27B1 gene, such as Q65H, R107H and P112L, can cause loss of enzyme activity, resulting in severe phenotypes ( 14 ). Other mutations, such as G57V, G73W and R459C, are associated with moderate to severe phenotypes ( 14 ). VDDR-1A was first reported internationally in 1961( 15 ), in which children carrying mutations exhibited symptoms from 6 months to 2 years of age.…”

An overview of CYP27B1 enzyme mutation and management: A case report and review of the literature

“…They concluded that physiological doses of calcitriol (0.25–0.75 μg/day) could improve the clinical and laboratory profile of the patients. Both cases in the Dhull et al 16 study received 30 ng/kg/day and 2 mmols/kg/day calcitriol and phosphate, respectively. Based on the positive feedback received, the calcitriol dose was changed to 20 ng/kg/day in the first case and to 10 ng/kg/day in the second case.…”

An overview of CYP27B1 enzyme mutation and management: A case report and review of the literature

“…Then, after positive feedback, the calcitriol dosage was modified; it was set to 20 ng/kg/day in the first case and reduced to 10 ng/kg/ day in the second case. Also, over the course of treatment, phosphate supplementation was reduced and then discontinued (43).…”