Calcium and vitamin D metabolism in hypocalcemic vitamin D-resistant rickets carriers.
OBJECTIVE
Hypocalcemic vitamin D-resistant rickets (HVDRR) is a rare monogenic autosomal recessive disorder associated with mutations in the gene of the vitamin D receptor (VDR), the mediator of 1,25(OH)2D3 action. Although many investigations have discussed the clinical manifestations and molecular etiology of this disease, only a few have investigated the biochemical and hormonal status of heterozygous HVDRR. The aim of the current work was to investigate the profile of selected biochemical and hormonal parameters related to the vitamin D endocrine system in a large number of HVDRR heterozygotes.


METHODS
67 relatives of 2 HVDRR patients, all members of an extended Greek kindred of five generations with a common ancestor, were included in the study. Direct sequencing was used to identify VDR gene mutations. Serum Ca, P, 25(OH)D, iPTH, and 1,25(OH)2D levels were determined in all members of the kindred.


RESULTS
DNA analysis of the participants led to the design of two study groups: the HVDRR carriers (24) and the control subjects (43). Our results showed elevated circulating serum levels of 1,25(OH)2D3 and lower levels of PTH than their age- and sex-matched controls. No hypocalcemia or hypophosphatemia were detected in HVDRR carriers.


CONCLUSIONS
Our findings suggest that HVDRR carriers may have compensatory elevated serum levels of 1,25(OH)2D3 through which they restrain PTH secretion. The study of HVDRR carriers could be a useful tool for the investigation of the vitamin D endocrine system.
Nicolaidou
Polyxeni
P
Third Department of Pediatrics, Athens University Medical School, University General Hospital Attikon, Chaidari, Greece. pedatt@med.uoa.gr
Papadopoulou
Anna
A
Georgouli
Helen
H
Matsinos
Y G
YG
Tsapra
Helen
H
Fretzayas
Andreas
A
Giannoulia-Karantana
Aglaia
A
Kitsiou
Sophia
S
Douros
Konstantinos
K
Papassotiriou
Ioannis
I
Chrousos
Georges P
GP
D000293:Adolescent; D000328:Adult; D000368:Aged; D002118:Calcium / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006580:Genetic Carrier Screening; D006115:Greece / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D007015:Hypophosphatemia, Familial / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D002118:Calcium