Search for a rare disease
Other search option(s)
Hypocalcemic vitamin D-resistant rickets
A rare genetic, disorder of vitamin D metabolism characterized by hypocalcemia, severe rickets and in many cases alopecia.
ORPHA:93160Classification level: Disorder
- Hereditary vitamin D-resistant rickets
- VDDR II
- VDRR II
- Vitamin D-dependent rickets type II
- Vitamin D-resistant rickets type II
- Prevalence: Unknown
- Inheritance: Autosomal recessive
- Age of onset: Infancy, Neonatal
- ICD-10: E83.3
- ICD-11: 5C63.21
- OMIM: 277440 600785 619073
- UMLS: C3536983
- MeSH: -
- GARD: -
- MedDRA: -
The prevalence is unknown.
Progressive rickets manifest during the first years of life with poor growth and skeletal deformities. Total body alopecia is present in severe forms of the disease (2/3 of cases). In some cases, skin lesions or epidermal cysts can be observed along with alopecia. The disease presents a broad clinical picture that largely depends on the genotype.
The disease is due to mutations in the vitamin D receptor gene (VDR; 12q13-14) that decrease the receptor's action thereby preventing calcitriol's action. This leads to an impaired intestinal absorption of calcium and phosphate.
Diagnosis is based on clinical, biochemical and radiological findings. Biochemical features are severe hypocalcemia, hypophosphatemia, secondary hyperparathyroidism, normal serum levels of calcidiol (25-hydroxyvitamin D), elevated serum levels of calcitriol (1,25-dihydroxyvitamin D3, the active form of vitamin D), and high serum levels of alkaline phosphatase. Radiological findings include typical rickets and/or osteomalacia and decreased bone mineralization. Osteitis fibrosa cystica due to secondary hyperparathyroidism is commonly observed.
Differential diagnosis includes other forms of rickets (hereditary and nutritional) and atrichia with papular lesions (APL) and hypocalcemic vitamin D-dependent rickets.
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them that there is a 25% risk of having an affected child at each pregnancy.
Management and treatment
Treatment aims at improving growth, correcting hypocalcemia and hyperparathyroidism, and at enhancing mineralization of bones. In patients with mild forms it consists of daily administration of high doses of calcitriol and calcium; intravenous administration may be needed in severe phenotypes. Response to treatment largely depends on the severity of the disease. Patients with alopecia generally do not respond to oral treatment and need intravenous calcium infusions. Regular monitoring of biochemical parameters is required.
Correction of rachitic deformities depends on the severity of the disease.
A summary on this disease is available in Français (2022) Nederlands (2022) Greek (2012, pdf)