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Hypocalcemic vitamin D-dependent rickets

ORPHA289157
Synonym(s) 1-alpha-hydroxylase deficiency
PDDRI
Pseudovitamin D-deficient rickets
VDDI
VDDR-I
Vitamin D dependent rickets type I
Vitamin D-dependency type I
Prevalence 1-5 / 10 000
Inheritance Autosomal recessive
Age of onset Infancy
Neonatal
ICD-10
  • E55.0
OMIM
UMLS -
MeSH -
MedDRA -

Summary

Hypocalcemic vitamin D-dependent rickets (VDDR-I) is an early-onset hereditary vitamin D metabolism disorder characterized by severe hypocalcemia leading to osteomalacia and rachitic bone deformations, and moderate hypophosphatemia.

The prevalence at birth is estimated at around 1/2,000. The disease is more frequent in the French Canadian population in the Saguenay region of Quebec.

The disease manifests within the first year of life with hypotonia, tetany, seizures, muscle weakness, and poor growth. Progressively, patients present with rachitic deformities (bowed legs, rachitic rosary...). Enamel hypoplasia is occasionally observed.

The disease is due to inactivating mutations in the CYP27B1 gene (12q14) that codes for 1-alpha-hydroxylase which converts the vitamin D precursor calcidiol to calcitriol, the vitamin D active metabolite. This defect in the synthesis of vitamin D leads to defective intestinal absorption of calcium and phosphate.

Diagnosis is based on biochemical and radiological findings. Classic radiological signs of rickets are skeletal anomalies of the growth plates and metaphyseal bones, osteomalacia, and osteoporosis. Biochemical findings are severe hypocalcemia and moderate hypophosphatemia. Additional biochemical anomalies include normal serum levels of calcidiol (25-hydroxyvitamin D) associated with low serum levels of calcitriol (1,25-dihydroxyvitamin D3), aminoaciduria and elevated peripheral parathyroid hormone concentrations. Bone biopsy can reveal osteomalacia. Diagnosis is confirmed by DNA analysis.

Differential diagnosis includes nutritional vitamin D deficiency, vitamin D resistant rickets (see this term) and bone dysplasia.

Transmission is autosomal recessive.

Treatment aims at improving growth and restoring normal serum levels of calcium, phosphorus, alkaline phosphatase, and parathyroid hormone and at healing/preventing skeletal deformities. It consists of daily administration of large doses of vitamin D and physiologic doses of calcitriol. Nephrocalcinosis, hypercalciuria, and hypercalcemia can be observed as complications of the therapy. Regular monitoring (physical and biochemical examination, hand radiographs, renal ultrasound) is thus required.

With treatment, prognosis is good.

Expert reviewer(s)

  • Dr Harald JÜPPNER

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