Skeletal Abnormalities and VDR1 Gene Polymorphisms in Mucopolysaccharidosis Patients

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.

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.

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).

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.

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.