Synonyms: pseudo-vitamin D deficiency rickets Type I, vitamin D-dependent rickets Type I, VDDR I
Inheritance: autosomal recessive
Genetic locus: chromosome 12q13.3
Molecular defect: deficiency in 1-alpha hydroxylase; this results in decreased production of 1,25 dihydroxy vitamin D3
Clinical features:
(1) normal at birth with onset in during infancy or early childhood
(2) severe muscle weakness with tetany
(3) rickets in young children and osteomalacia in adults
(4) seizures
Laboratory features:
(1) very low serum levels of 1,25 dihydroxy vitamin D
(2) low serum calcium
(3) high serum parathyroid hormone (PTH)
Management - Patients respond well to replacement therapy with high doses of vitamin D:
(1) 1-alpha-hydroxy vitamin D3
(2) 1,25-dihydroxyvitamin D3
(3) 25-hydroxyvitamin D3
(4) dihydrotachysterol
According to Liberman and Marx (page 4229) the daily replacement dose must be very high, sufficient to maintain serum 1,25-dihydroxyvitamin D3 at levels 3 to 150 times the upper limit of normal (65 pg/mL), i.e. at levels from 200 to 10,000 pg/mL.
