Alsharhan Hind, Haider Mohammad Z, Qadoura Bann, Ayed Mariam, Dhaunsi Gursev S, Alkandari Hessa
Department of Pediatrics, Farwaniya Hospital, Ministry of Health, Sabah Al-Nasser, Kuwait.
Department of Pediatrics, Health Sciences Centre, College of Medicine, Kuwait University, Safat, Kuwait.
Front Pediatr. 2024 Jul 15;12:1376053. doi: 10.3389/fped.2024.1376053. eCollection 2024.
Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder characterized by deficient or absent -L-iduronidase (IDUA) enzyme activity due to pathogenic variants in the gene. Early treatment with hematopoietic stem cell transplantation and/or enzyme replacement therapy is associated with improved outcomes in this progressive multisystem disease. The diagnosis is usually delayed due to late presentation and non-specific symptoms, which result in high morbidity and mortality. The incidence of MPS I is unknown in Kuwait. This pilot study was undertaken to screen MPS I in all Kuwaiti neonates born at Farwaniya Hospital (FH), a major center in Kuwait, over 12 months. This study examined the incidence of MPS I for inclusion in the national newborn screening (NBS) to enable its early detection and adequate treatment. All Kuwaiti neonates born at FH between December 2021 and December 2022 were screened for MPS I. The screening consisted of determining IDUA enzyme activity in dried blood spot-derived samples using tandem mass spectrometry. A follow-up genetic analysis of the gene has been planned to screen the cases with diminished IDUA enzyme activity as second-tier testing. A total of 618 newborns, including 331 (54%) boys and 287 (46%) girls, were screened. Of them, 20 had deficient IDUA enzyme activity but showed negative genetic testing. However, we have diagnosed one additional female infant with MPS I who belonged to FH, but the parents chose to deliver in a private hospital. The molecular genetic study revealed the presence of a previously reported pathogenic nonsense variant in the c.1882C>T, which is associated with severe phenotype. That being included, MPS I is estimated to be approximately 0.2% of all screened cases in Kuwait. Our study is the first to evaluate the incidence of MPS I in Kuwait. Given the single center, small number of screened infants, and the short study duration thus far, it is premature to calculate the incidence. It is anticipated that as the study continues, we would be able to estimate the incidence in our population correctly. Screening newborns in all maternity hospitals in Kuwait is necessary to calculate the actual incidence of this severe disorder. Still, our preliminary data support the inclusion of MPS I in national NBS program to allow early initiation of treatment and thus improve disease outcome.
黏多糖贮积症I型（MPS I）是一种常染色体隐性溶酶体贮积病，其特征是由于IDUA基因的致病变异导致α-L-艾杜糖醛酸酶（IDUA）活性缺乏或缺失。对于这种进行性多系统疾病，早期进行造血干细胞移植和/或酶替代疗法与改善预后相关。由于出现症状较晚且症状不具特异性，诊断通常会延迟，这导致了高发病率和高死亡率。在科威特，MPS I的发病率尚不清楚。本试点研究旨在对科威特主要医疗中心法瓦尼亚医院（FH）在12个月内出生的所有科威特新生儿进行MPS I筛查。本研究调查了MPS I的发病率，以便将其纳入国家新生儿筛查（NBS），从而实现早期检测和适当治疗。对2021年12月至2022年12月期间在FH出生的所有科威特新生儿进行了MPS I筛查。筛查包括使用串联质谱法测定干血斑样本中的IDUA酶活性。已计划对IDUA酶活性降低的病例进行后续基因分析，作为二线检测。共筛查了618名新生儿，其中包括331名（54%）男孩和287名（46%）女孩。其中，20名新生儿的IDUA酶活性不足，但基因检测呈阴性。然而，我们又诊断出一名属于FH的MPS I女婴，但父母选择在一家私立医院分娩。分子遗传学研究显示，IDUA基因存在一个先前报道的致病性无义变异c.1882C>T，该变异与严重表型相关。综上所述，MPS I估计约占科威特所有筛查病例的0.2%。我们的研究是首次评估科威特MPS I的发病率。鉴于目前是单中心研究，筛查的婴儿数量较少，且研究持续时间较短，现在计算发病率还为时过早。预计随着研究的继续，我们将能够正确估计我国人群中的发病率。有必要对科威特所有妇产医院的新生儿进行筛查，以计算这种严重疾病的实际发病率。尽管如此，我们的初步数据支持将MPS I纳入国家NBS计划，以便尽早开始治疗，从而改善疾病预后。
