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J Pediatr Endocrinol Metab. 2018 Aug 28;31(8):861-868. doi: 10.1515/jpem-2017-0312.

Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR): clinical heterogeneity and long-term efficacious management of eight patients from four unrelated Arab families with a loss of function VDR mutation.

Author information

1
Department of Pathology, Molecular Genetics Pathology Unit, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
2
Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
3
Department of Pediatrics - MBC 58, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
4
Department of Pathology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
5
Department of Orthopedic, King Saud University, Riyadh, Saudi Arabia.
6
Genome Technologies, Ontario Institute for Cancer Research, Toronto, Canada.

Abstract

BACKGROUND:

Vitamin D regulates the concentrations of calcium and phosphate in blood and promotes the growth and remodeling of bones. The circulating active form of vitamin D, 1,25-dihydroxyvitamin D, binds to the vitamin D receptor (VDR), which heterodimerizes with the retinoid X receptor to regulate the expression of target genes. Inactivating mutations in the VDR gene cause hereditary vitamin D-resistant rickets (HVDRR), a rare disorder characterized by an early onset of rickets, growth retardation, skeletal deformities, hypocalcemia, hypophosphatemia and secondary hyperparathyroidism, and in some cases alopecia.

METHODS:

We describe eight new HVDRR patients from four unrelated consanguineous families. The VDR gene was sequenced to identify mutations. The management of patients over a period of up to 11 years following the initial diagnosis is assessed.

RESULTS:

Although all patients exhibit main features of HVDRR and carry the same c.885C>A (p.Y295*) loss of function mutation in the VDR gene, there was heterogeneity of the manifestations of HVDRR-associated phenotypes and developmental milestones. These eight patients were successfully treated over a period of 11 years. All clinical symptoms were improved except alopecia.

CONCLUSIONS:

The study concludes that VDR sequencing and laboratory tests are essential to confirm HVDRR and to assess the effectiveness of the treatment.

KEYWORDS:

alopecia; growth retardation; hereditary 1,25-dihydroxyvitamin D-resistant rickets; treatment; vitamin D receptor mutation

PMID:
29949513
DOI:
10.1515/jpem-2017-0312
[Indexed for MEDLINE]

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