Vitamin D Hydroxylation-Deficient Rickets, Type 1b

A number sign (#) is used with this entry because vitamin D-dependent rickets type 1B, due to a defect in vitamin D 25-hydroxylation, is caused by mutation in the CYP2R1 gene (608713) on chromosome 11p15.

For a general phenotypic description and discussion of genetic heterogeneity of rickets due to disorders in vitamin D metabolism or action, see vitamin D-dependent rickets type 1A (VDDR1A; 264700).

Clinical Features

Casella et al. (1994) described 2 brothers of Nigerian descent who had rickets at a young age despite a history of adequate vitamin D intake. The patient had bone abnormalities of the legs appearing between 2 and 7 years of age. Before treatment, he had low normal serum calcium levels, low serum phosphate levels, elevated serum alkaline phosphatase levels, normal serum levels of 1-alpha,25-dihydroxyvitamin D, and low 25-hydroxyvitamin D. Treatment with vitamin D2 in pharmacologic doses resulted in resolution of the biochemical abnormalities and radiographic deformities. High levels of vitamin D2 were required to maintain normal concentrations of 25-hydroxyvitamin D in the serum even though vitamin D absorption was normal. The unique biochemical profile enabled exclusion of other causes of vitamin D-dependent rickets could be excluded (e.g., VDDR1A and VDDR2A, 277440). Cheng et al. (2004) noted that the scarcity of cases of 25-hydroxylase deficiency may reflect genetic polymorphisms that allow alternate pathways to function in some individuals. It may be significant that the patient studied by Cheng et al. (2004) was Nigerian. Individuals with dark skin require exposure to sunlight for longer periods of time to generate requisite levels of vitamin D3 as compared with those of less skin pigmentation and thus may be more sensitive to impaired synthesis of the vitamin.

Molecular Genetics

In one of the patients described by Casella et al. (1994), Cheng et al. (2004) identified a homozygous mutation in the CYP2R1 gene (608713.0001).