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. 2021 Mar 17:14:349-358.
doi: 10.2147/PGPM.S295241. eCollection 2021.

Skeletal Abnormalities and VDR1 Gene Polymorphisms in Mucopolysaccharidosis Patients

Camelia Alkhzouz  1   2 , Georgiana Cabau  2 , Cecilia Lazea  2   3 , Carmen Asavoaie  3 , Simona Bucerzan  1   2 , Andreea Manuela Mirea  2 , Marius Farcas  2 , Maria Miclaus Jnr  2 , Radu Popp  2 , Diana Miclea  1   2
Affiliations

Skeletal Abnormalities and VDR1 Gene Polymorphisms in Mucopolysaccharidosis Patients

Camelia Alkhzouz et al. Pharmgenomics Pers Med. .

Abstract

Introduction: Articular and bone damage, which is so disabling in Mucopolysaccharidosis (MPS), requires attention as to the explanatory bias of the pathogenetic mechanisms identified to date. The vitamin D receptor (VDR) has been investigated in many studies in correlation with bone metabolism, osteoporosis, and the impaired bone mineral density associated with certain polymorphisms of the VDR gene.

Aim: This study aims to observe whether there is an association between clinical features, phospho-calcium metabolism parameters and the VDR gene polymorphisms in patients with MPS.

Patients and method: We evaluated six patients with MPS type I, 20 patients with MPS type II, two patients with MPS types IIIA and IIIB and three patients with MPS type IVB. In these patients, phospho-calcium metabolism, markers of bone formation, bone radiographs and bone densitometry were evaluated, as were four polymorphisms of the VDR gene (ApaI, BsmI, FokI and TaqI).

Results: There was a deficiency in 25 hydroxy vitamin D in MPS type I patients at the final evaluation and in MPS type II patients, both at ERT initiation and at the last evaluation. The analysed polymorphisms were not associated with modified calcium-phosphor levels, but some differences were observed regarding the level of 25 OH vitamin D. Thus, in the case of AA polymorphism, all patients have a 25 OH vitamin D deficiency, and one patient with the AA genotype and three with Aa have a 25 OH vitamin D deficiency and secondary hyperparathyroidism due to this deficiency (four patients), all of them having the Bb phenotype.

Conclusion: In MPS patients, vitamin D deficiency is observed, as it is in some patients with secondary hyperparathyroidism, which indicates vitamin D supplementation to protect bone metabolism. There are no obvious correlations between VDR polymorphism and bone metabolism in MPS patients.

Keywords: ApaI; BsmI; FokI; TaqI; mucopolysaccharidosis; vitamin D receptor.

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Conflict of interest statement

Dr. Camelia Alkhzouz, Dr. Carmen Asavoaie and Dr. Diana Miclea report personal fees from Speaker in conference organized by Takeda Pharmaceuticals Company, Romania, “News on integrated care and management of patients with Hunter’s syndrome”, Cluj Napoca, 08 November 2019. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Radiological abnormalities seen in our patients with MPS type II. (A) Macrocephaly in 6 years old MPS II patient; (B) i,ii. Dorsolumbar kyphosis and a hypoplastic transitional vertebra with anterior beaking; (C) Short, thick clavicles, paddle-shaped ribs, scoliosis; (D) Round and flared iliac wings, an underdeveloped acetabulum and signs of hip dysplasia; (E) i,ii. Thick and hypoplastic distal radius and ulna creating a V-shaped deformity (Madelung deformity); small/underdeveloped carpal bones; bullet-shaped phalanges; (F) i,ii,iii. Small and hypoplastic tarsal bones and calcaneovalgus deformity.
See this image and copyright information in PMC

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