PDF(Pubmed)
Abstract：
Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder characterized by deficient or absent α-L-iduronidase (IDUA) enzyme activity due to pathogenic variants in the IDUA 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 IDUA 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 IDUA 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.
摘要：
I型粘多糖贮积症（MPSI）是一种常染色体隐性遗传溶酶体贮积症，其特征是由于IDUA基因中的致病性变体而缺乏或缺乏α-L-艾杜糖醛酸酶（IDUA）酶活性。造血干细胞移植和/或酶替代疗法的早期治疗与这种进行性多系统疾病的改善结果相关。诊断通常由于晚期表现和非特异性症状而延迟。导致高发病率和死亡率。科威特MPSI的发病率未知。这项试点研究是为了在Farwaniya医院(FH)出生的所有科威特新生儿中筛查MPSI，科威特的一个主要中心，超过12个月。这项研究检查了纳入国家新生儿筛查（NBS）的MPSI的发生率，以使其能够早期发现和适当治疗。对2021年12月至2022年12月在FH出生的所有科威特新生儿进行了MPSI筛选。筛选包括使用串联质谱法确定干血点衍生样品中的IDUA酶活性。已计划对IDUA基因进行后续遗传分析，以筛选IDUA酶活性降低的病例，作为第二层测试。共有618名新生儿,包括331名(54%)男孩和287名(46%)女孩，被筛选。其中,20具有缺乏的IDUA酶活性，但显示出阴性的遗传测试。然而,我们已经诊断出另一个属于FH的MPSI女婴，但父母选择在私立医院分娩.分子遗传学研究表明，在IDUAc.1882C>T中存在先前报道的致病性无义变体，这与严重的表型有关。包括在内，据估计，MPSI约占科威特所有筛查病例的0.2%。我们的研究是第一个评估科威特MPSI发病率的研究。鉴于单一中心，少数接受筛查的婴儿，到目前为止，研究持续时间短，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们人群的发病率。为了计算这种严重疾病的实际发病率，必须在科威特所有妇产医院对新生儿进行筛查。尽管如此，我们的初步数据支持将MPSI纳入国家NBS计划,以允许早期开始治疗,从而改善疾病结局.
