Vitamin D-dependent Rickets Type 1A: Recognizing Clinical Clues to Avoid Delayed Diagnosis
Abstract
Vitamin D-dependent rickets type 1A (VDDR1A) is a rare, inherited form of rickets caused by biallelic mutations in the CYP27B1 gene, leading to 1α-hydroxylase deficiency and impaired 1,25-dihydroxyvitamin D (1,25(OH)₂D) production. We report the case of a 25-year-old woman who was initially diagnosed at 12 months of age with "vitamin D-resistant rickets" and presented with motor delay, skeletal deformities, and a history of multiple orthopedic surgeries. At 25 years of age, etiologic evaluation identified a homozygous CYP27B1 p.Thr325Met variant, classified as likely pathogenic by the testing laboratory but previously reported as a variant of uncertain significance. The condition's rarity and its clinical overlap with more common forms of rickets hindered early diagnosis. Treatment with calcitriol and mineral supplementation was followed by sustained biochemical improvement over approximately one year, although established skeletal deformities persisted. This report underscores the importance of clinical and laboratory recognition, genetic testing, individualized management, and cautious interpretation of rare genetic variants.
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