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Vitamin D-dependent rickets
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Vitamin D-dependent rickets

Vitamin D-dependent rickets is a group of disorders characterized by soft, weak bones due to the body's inability to properly use vitamin D.

Overview

Vitamin D-dependent rickets is a group of disorders characterized by soft, weak bones (rickets). In these conditions, the process of mineralizing developing bones is disrupted. People with these disorders have problems using vitamin D, which is essential for maintaining the proper levels of calcium and phosphate in the blood—minerals required for strong bones and teeth.

Signs and symptoms often begin in infancy and include weak muscle tone (hypotonia), failure to thrive, and abnormally curved (bowed) legs once the child begins to walk. Weakened bones are often painful and prone to fractures. Other features include delayed bone growth, short stature, and enlargement of the skull, wrists, and ends of the ribs. Dental abnormalities, such as delayed tooth formation and thin enamel, are also common. Very low blood calcium levels can lead to muscle cramps, tingling sensations (paresthesias), or seizures. Hair loss (alopecia) has been reported in some individuals with type 2A.

Frequency

The prevalence of vitamin D-dependent rickets is unknown. While common rickets (caused by dietary lack of vitamin D or insufficient sun exposure) affects approximately 24 in 100,000 people in the U.S. annually, genetic forms are much less common.

Causes

Pathogenic variants in several genes can cause vitamin D-dependent rickets. These genes provide instructions for proteins that help the body use vitamin D. Vitamin D must undergo two biochemical reactions to become the fully active form, called calcitriol.

  • CYP27B1 and CYP2R1: These genes provide instructions for enzymes that help convert vitamin D to calcitriol. Variants here reduce or eliminate enzyme activity, impairing this conversion.
  • VDR: This gene produces vitamin D receptors. Variants here lead to changes in the VDR protein, preventing the receptor from properly interacting with calcitriol or DNA, which impairs gene activity involved in calcium regulation.

The inability to regulate calcium also impairs phosphate regulation, leading to low blood levels of calcium (hypocalcemia) and phosphate (hypophosphatemia), which disrupts bone mineralization.

Genes Associated with Vitamin D-dependent Rickets

  • CYP27B1
  • CYP2R1
  • VDR

Inheritance

Types VDDR1A, VDDR1B, and VDDR2A are usually inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell must have a pathogenic variant. VDDR3 is typically inherited in an autosomal dominant pattern, where one copy of the altered gene is sufficient to cause the disorder. Some individuals with a variant in one copy of the CYP2R1 gene show mild symptoms, a pattern known as incomplete autosomal dominance.

Frequently Asked Questions

Therapy focuses on providing the active form of vitamin D (calcitriol) or analogs such as alfacalcidol, often combined with oral calcium supplements to maintain normal serum calcium and phosphate. Doses are individualized based on serial labs (calcium, phosphate, alkaline phosphatase, PTH) and growth parameters, and adjustments are made every 3–6 months.
Nutritional rickets results from insufficient vitamin D intake or sunlight exposure, and it usually responds to standard vitamin D supplementation. Vitamin D‑dependent rickets is caused by genetic defects (e.g., CYP27B1, CYP2R1, VDR) that impair the activation or action of vitamin D, so regular vitamin D doses are ineffective. Diagnosis requires measuring serum 1,25‑dihydroxyvitamin D (calcitriol) levels and confirming a pathogenic gene mutation.
Initially, calcium, phosphate, alkaline phosphatase, and urinary calcium excretion are checked every 2–4 weeks to avoid hypercalcemia. Once stable, monitoring can be spaced to every 3–6 months, with additional checks during growth spurts, illness, or medication changes.
If calcium and phosphate are kept in the normal range, most skeletal deformities improve, but residual growth retardation, dental enamel defects, and, rarely, nephrocalcinosis can occur. Regular orthopedic assessments, dental exams, and renal ultrasounds are recommended to detect and manage these issues early.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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