Department of Pediatric Genetics, Istanbul University-Cerrahpasa, Medical School, Istanbul, Turkey.
Department of Pediatric Genetics, Istanbul University-Cerrahpasa, Medical School, Istanbul, Turkey.
Gene. 2019 Jul 1;704:59-67. doi: 10.1016/j.gene.2019.04.026. Epub 2019 Apr 11.
Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by biallelic mutations in GALNS gene and characterized by progressive skeletal deformities with short stature. The aim of this study was to evaluate the genotype, longitudinal height measurement and clinical features of MPS IVA patients. Thirty-two patients from 22 families were enrolled. The ages of patients at diagnosis ranged from two months to 18 years of age, and followed up for three to twenty years. They were classified as severe and attenuated form (intermediate and mild) according to their height measurements. The mean height standard deviation scores (SDS) for Turkish standards at 0-3, 5 and 10 years of ages were found to be -1.1, -4.2 and -7.3 respectively in patients with severe phenotype, while they were +0.4, -1.5 and -3 for intermediate phenotype. Patients with severe form reached a mean final height of -8.5 SDS, and mild phenotype -3.6 SDS. The most common initial and current symptoms in the patients with the severe phenotype were pectus carinatus and/or kyphosis deformities which occurred between 5 months and 3 years of age, and genu valgum deformity which developed after 3 years of age. However, kyphoscoliosis was the most common initial and current findings in the attenuated phenotype. Although, initial symptoms appeared in early childhood in the intermediate phenotype, similar to the severe phenotype, the clinical findings progressed slowly and genu valgum deformity did not develop. In patients with mild phenotype, the onset of symptoms was after 5 years of age. In conclusion, this study provides significant insights into the initial and follow-up clinical features and height values that contribute to the differential diagnosis of the severe and intermediate phenotypes in early childhood. Eleven mutations in GALNS gene in which one of them is novel (c.416G>A) were associated with the severe phenotype and three mutations (c.1038C>A, c.850T>G, c.752G>A) lead to the attenuated phenotype.
黏多糖贮积症 IVA（MPS IVA）是一种溶酶体贮积病，由 GALNS 基因的双等位基因突变引起，其特征为进行性骨骼畸形和身材矮小。本研究旨在评估 MPS IVA 患者的基因型、纵向身高测量和临床特征。共纳入 22 个家系的 32 例患者。患者的诊断年龄为 2 个月至 18 岁，随访 3 至 20 年。根据身高测量结果，他们分为严重型和衰减型（中间型和轻度型）。严重表型患者在 0-3、5 和 10 岁时，根据土耳其标准的身高标准差评分（SDS）分别为-1.1、-4.2 和-7.3，而中间表型患者则分别为+0.4、-1.5 和-3。严重表型患者的平均最终身高 SDS 为-8.5，轻度表型为-3.6。严重表型患者最初和当前最常见的症状是鸡胸和/或脊柱后凸畸形，发生在 5 个月至 3 岁之间，以及 3 岁后出现的膝外翻畸形。然而，衰减表型中最常见的最初和当前发现是脊柱侧凸。尽管中间表型的初始症状出现在儿童早期，但与严重表型相似，临床发现进展缓慢，且不会出现膝外翻畸形。轻度表型患者的症状发生在 5 岁以后。总之，本研究为严重和中间表型在儿童早期的鉴别诊断提供了重要的初始和随访临床特征和身高值。GALNS 基因中的 11 个突变（其中一个为新突变（c.416G>A））与严重表型相关，3 个突变（c.1038C>A、c.850T>G、c.752G>A）导致衰减表型。
