Molybdenum Cofactor Deficiency Type A disease in Northern Israel.

IF 1.8 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL
Israel Medical Association Journal Pub Date : 2025-03-01
Eliyahu Fund, Hanna Mandel, Yoav Zehavi, Ronen Spiegel
{"title":"Molybdenum Cofactor Deficiency Type A disease in Northern Israel.","authors":"Eliyahu Fund, Hanna Mandel, Yoav Zehavi, Ronen Spiegel","doi":"","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Molybdenum cofactor deficiency (MoCD) is a group of three autosomal recessive disorders caused by deficiency of the de novo metabolic synthesis of molybdenum cofactor. Most patients present within the first weeks of life with intractable seizures and progressive encephalopathy. Type A is the most common form caused by pathogenic variants in MOCS1 gene that result in deficiency of the first enzyme, cyclic pyranopterin monophosphate synthase.</p><p><strong>Objectives: </strong>To characterize MoCD type A clinical features, disease course, neuroradiology, and genetic features in Northern Israel.</p><p><strong>Methods: </strong>In this retrospective study, we collected the clinical, brain imaging, and genetic data of confirmed MoCD type A patients in Northern Israel.</p><p><strong>Results: </strong>The study included 10 confirmed MoCD type A patients (6 males, 4 females), all deceased. The patients were of consanguineous families. Nine patients were of Arab Muslim ethnicity and one was of Druze origin. A total of four different homozygous genotypes were identified. All patients presented initially between 1-4 days of life. Three died within the first month of life, five within the first year of life, and only two died after the age of 7 years. All patients who survived beyond the first month developed profound global developmental delays, had poorly controlled epilepsy, and developed severe microcephaly.</p><p><strong>Conclusions: </strong>Although MoCD type A is an ultra-rare disease worldwide, it is relatively common in northern Israel due to several founder mutations and high consanguinity. All the patients presented the severe neonatal form of the disease with significant neurological deterioration and early lethality within infancy and childhood.</p>","PeriodicalId":50268,"journal":{"name":"Israel Medical Association Journal","volume":"27 3","pages":"142-146"},"PeriodicalIF":1.8000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Israel Medical Association Journal","FirstCategoryId":"3","ListUrlMain":"","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0

Abstract

Background: Molybdenum cofactor deficiency (MoCD) is a group of three autosomal recessive disorders caused by deficiency of the de novo metabolic synthesis of molybdenum cofactor. Most patients present within the first weeks of life with intractable seizures and progressive encephalopathy. Type A is the most common form caused by pathogenic variants in MOCS1 gene that result in deficiency of the first enzyme, cyclic pyranopterin monophosphate synthase.

Objectives: To characterize MoCD type A clinical features, disease course, neuroradiology, and genetic features in Northern Israel.

Methods: In this retrospective study, we collected the clinical, brain imaging, and genetic data of confirmed MoCD type A patients in Northern Israel.

Results: The study included 10 confirmed MoCD type A patients (6 males, 4 females), all deceased. The patients were of consanguineous families. Nine patients were of Arab Muslim ethnicity and one was of Druze origin. A total of four different homozygous genotypes were identified. All patients presented initially between 1-4 days of life. Three died within the first month of life, five within the first year of life, and only two died after the age of 7 years. All patients who survived beyond the first month developed profound global developmental delays, had poorly controlled epilepsy, and developed severe microcephaly.

Conclusions: Although MoCD type A is an ultra-rare disease worldwide, it is relatively common in northern Israel due to several founder mutations and high consanguinity. All the patients presented the severe neonatal form of the disease with significant neurological deterioration and early lethality within infancy and childhood.

以色列北部缺钼辅助因子A型疾病
背景:钼辅助因子缺乏症(MoCD)是一组由钼辅助因子新生代谢合成缺乏引起的三种常染色体隐性遗传病。大多数患者在出生后的头几周出现难治性癫痫发作和进行性脑病。A型是最常见的形式,由MOCS1基因的致病性变异引起,导致第一种酶环吡蝶呤单磷酸合成酶缺乏。目的:了解以色列北部MoCD A型的临床特征、病程、神经放射学和遗传特征。方法:在这项回顾性研究中,我们收集了以色列北部确诊的MoCD A型患者的临床、脑成像和遗传资料。结果:纳入确诊MoCD A型患者10例(男6例,女4例),均已死亡。这些病人都是近亲。9名患者为阿拉伯穆斯林,1名德鲁兹裔。共鉴定出4种不同的纯合基因型。所有患者最初出现在生命的1-4天之间。其中3人在出生后一个月内死亡,5人在出生后一年内死亡,只有2人在7岁以后死亡。所有存活超过第一个月的患者都出现了严重的全面发育迟缓,癫痫控制不佳,并发展为严重的小头畸形。结论:尽管MoCD A型在世界范围内是一种极其罕见的疾病,但由于几个始祖突变和高血缘关系,在以色列北部相对常见。所有患者均表现为严重的新生儿形式,在婴儿期和儿童期出现明显的神经功能恶化和早期死亡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Israel Medical Association Journal
Israel Medical Association Journal 医学-医学:内科
CiteScore
2.20
自引率
12.50%
发文量
54
审稿时长
3-8 weeks
期刊介绍: The Israel Medical Association Journal (IMAJ), representing medical sciences and medicine in Israel, is published in English by the Israel Medical Association. The Israel Medical Association Journal (IMAJ) was initiated in 1999.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信