Vitamin D-Dependent Rickets Type 1B (25-Hydroxylase Deficiency): A Rare Condition or a Misdiagnosed Condition?
Level 4 - case-series / case-control
Case series of affected families combined with in vitro functional studies
PubMed 28548312 · doi:10.1002/jbmr.3181
What was done
Researchers evaluated 7 patients from 2 unrelated families presenting with homozygous loss-of-function mutations in CYP2R1 and their heterozygous unaffected parents. Genetic sequencing and in vitro enzymatic activity assays were performed, and clinical, biochemical, radiographic, and bone densitometry responses to treatments—including alfacalcidol (1α-OH-D3) and calcifediol (25-OH-D3)—were evaluated.
What was found
Genetic analysis identified a novel c.124_138delinsCGG variation and a previously reported c.296T>C mutation in CYP2R1, both confirmed to cause loss of enzymatic function in vitro. Patients demonstrated very low 25-OH-D alongside normal or elevated 1,25-(OH)2D concentrations. Siblings exhibited three stages of rickets, whereas adult patients maintained normal mineral metabolism without vitamin D supplementation. Treatment with 1α-OH-D3 produced partial improvement and a dramatic increase in serum 1,25-(OH)2D, whereas 25-OH-D3 treatment resulted in dramatic clinical, biochemical, and bone densitometry improvements alongside normal CYP24A1 activity. No specific numerical values were provided in the abstract.
Why it matters
This report expands the known genetic spectrum of vitamin D-dependent rickets type 1B and highlights a biochemical profile easily misdiagnosed as nutritional vitamin D deficiency. It supports calcifediol (25-OH-D) as an effective targeted replacement therapy.
Limits
The study is limited to a small sample size of 7 patients across 2 families without a control group. The abstract omits precise quantitative measurements, baseline laboratory values, and standardized treatment durations.
Cited by
- supports The CYP2R1 gene encodes the enzyme responsible for converting inactive supplemental vitamin D into calcifediol.