A Case of Vitamin-D-Dependent Rickets Type 1A with Normal 1,25-Dihydroxyvitamin D Caused by Two Novel Mutations of the CYP27B1 Gene.
BACKGROUND
Vitamin-D-dependent rickets 1A (VDDR-1A) is caused by mutations of the renal CYP27B1 gene and is a rare form of rickets. Herein, we report a 20-month-old toddler who presented with inability to walk and failure to thrive. The clinical, biochemical and radiological findings were consistent with a diagnosis of rickets, specifically of the genetic type due to increased 25-OH vitamin D stores.


RESULTS
Our patient was a compound heterozygote with 2 novel mutations: c.242G>A(p.Gly81Glu) and c.1144C>G (p.Pro382Ala) in the CYP27B1 gene. Analysis of both mutations with in silico models predicted a deleterious effect on 25-OH vitamin D 1α-hydroxylase function. Interestingly, the levels of 1,25-(OH)2 vitamin D were within normal limits. Our patient was initiated on 1α-hydroxyvitamin D (alfacalcidol) and supplemental calcium. Monitoring of bone metabolism showed a normalization of all bone metabolism serum indices after 3 months of therapy and, thereafter, only alfacalcidol was given at a maintenance dose. The clinical follow-up showed a dramatic improvement in musculoskeletal activity, and the patient regained acceleration in height and weight appropriate for his age.


CONCLUSIONS
This rare case report of VDDR-1A with normal levels of 1,25-(OH)2 vitamin D enhances our awareness for this type of rickets in clinical practice.
Division of Endocrinology and Diabetes, Department of Pediatrics, Medical School, University of Patras, Patras, Greece.
Aris
A
Giannakopoulos
Alexandra
A
Efthymiadou
Dionisios
D
Chrysis
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D019943:Amino Acid Substitution; D053098:Familial Hypophosphatemic Rickets / Q000097:blood / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage*; D007223:Infant; D008297:Male; D009154:Mutation; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
D006887:Hydroxycholecalciferols; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C000600378:CYP27B1 protein, human; C008088:alfacalcidol