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J Pediatr Genet 2024; 13(01): 043-049
DOI: 10.1055/s-0041-1736559
Case-Based Review

Vitamin D-Dependent Rickets Type 1A in Two Siblings with a Hypomorphic CYP27B1 Variant Frequent in the African Population

Joana de Brito Chagas 
1   Pediatric Department, Hospital Pediátrico, Centro Hospitalar Universitário de Coimbra (HP-CHUC), Coimbra, Portugal
,
Carolina Cordinhã
2   Pediatric Department, Pediatric Nephrology Unit, Hospital Pediátrico, Centro Hospitalar Universitário de Coimbra (HP-CHUC), Coimbra, Portugal
,
Carmen do Carmo
2   Pediatric Department, Pediatric Nephrology Unit, Hospital Pediátrico, Centro Hospitalar Universitário de Coimbra (HP-CHUC), Coimbra, Portugal
,
Cristina Alves
3   Department of Pediatric Orthopaedics, Hospital Pediátrico, Centro Hospitalar Universitário de Coimbra (HP-CHUC), Coimbra, Portugal
,
Karen E. Heath
4   Institute of Medical and Molecular Genetics, IdiPAZ, Hospital Universitario La Paz, UAM, Madrid, Spain
5   Skeletal Dysplasia Multidisciplinary Unit and ERN-BOND, Hospital Universitario La Paz, Madrid, Spain; CIBERER, ISCIII, Madrid, Spain
,
Sérgio B. Sousa
6   Medical Genetics Unit, Skeletal Dysplasia Multidisciplinary Centre and ERN-BOND, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
7   University Clinic of Genetics, Faculty of Medicine, Universidade de Coimbra, Coimbra, Portugal
,
Clara Gomes
2   Pediatric Department, Pediatric Nephrology Unit, Hospital Pediátrico, Centro Hospitalar Universitário de Coimbra (HP-CHUC), Coimbra, Portugal
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Abstract

Vitamin D-dependent type 1A rickets (VDDR-1A) is a rare autosomal recessive disease due to the inability to convert 25-hydroxyvitamin D [25(OH)D] to the active form 1.25-dihydroxyvitamin D [1.25(OH)2D] by the enzyme 25(OH)D-1α-hydroxylase leading to low or low-normal serum levels of [1.25(OH)2D].

We report two sisters with rickets in whom the diagnosis of VDDR-1A was a challenge. They had normal 1.25(OH)2D levels, which are unusual with this condition but may be explained by the identified genotype. Both have compound heterozygous for two, most likely, hypomorphic CYP27B1 alleles: the novel p.(Arg117Gly) variant, and p.(Ala129Thr), which are present in 0.43% of the African population.

This report illustrates the variability of clinical, laboratory, and radiological presentation between two sisters with the same genotype, during phases of faster or slower growth. Genetic testing was crucial for establishing the diagnosis that optimized the management and genetic counseling.

Keywords

rickets - children - vitamin D - osteomyelitis


Publikationsverlauf

Eingereicht: 24. April 2021

Angenommen: 15. September 2021

Artikel online veröffentlicht:
25. Oktober 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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