Maple syrup urine disease: Clinical outcomes, metabolic control, and genotypes in a screened population after four decades of newborn bloodspot screening in the Republic of Ireland,Journal of Inherited Metabolic Disease

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Maple syrup urine disease: Clinical outcomes, metabolic control, and genotypes in a screened population after four decades of newborn bloodspot screening in the Republic of Ireland
Journal of Inherited Metabolic Disease ( IF 4.2 ) Pub Date : 2020-12-09 , DOI: 10.1002/jimd.12337
Daniel O'Reilly ₁ , Ellen Crushell ₁ , Joanne Hughes ₁ , Stephanie Ryan ₂ , Yvonne Rogers ₁ , Ingrid Borovickova _{3,

4} , Philip Mayne _{3,

4} , Michael Riordan ₅ , Atif Awan ₅ , Kevin Carson ₆ , Kim Hunter ₆ , Bryan Lynch ₇ , Amre Shahwan ₇ , Véronique Rüfenacht ₈ , Johannes Häberle ₈ , Eileen P Treacy ₉ , Ahmad A Monavari ₁ , Ina Knerr ₁

Affiliation

Since 1972, 18 patients (10 females/8 males) have been detected by newborn bloodspot screening (NBS) with neonatal‐onset maple syrup urine disease (MSUD) in Ireland. Patients were stratified into three clusters according to clinical outcome at the time of data collection, including developmental, clinical, and IQ data. A fourth cluster comprised of two early childhood deaths; a third patient died as an adult. We present neuroimaging and electroencephalography together with clinical and biochemical data. Incidence of MSUD (1972‐2018) was 1 in 147 975. Overall good clinical outcomes were achieved with 15/18 patients alive and with essentially normal functioning (with only the lowest performing cluster lying beyond a single SD on their full scale intelligence quotient). Molecular genetic analysis revealed genotypes hitherto not reported, including a possible digenic inheritance state for the BCKDHA and DBT genes in one family. Treatment has been based on early implementation of emergency treatment, diet, close monitoring, and even dialysis in the setting of acute metabolic decompensation. A plasma leucine ≥400 μmol/L (outside therapeutic range) was more frequently observed in infancy or during adolescence, possibly due to infections, hormonal changes, or noncompliance. Children require careful management during metabolic decompensations in early childhood, and this represented a key risk period in our cohort. A high level of metabolic control can be achieved through diet with early implementation of a “sick day” regime and, in some cases, dialysis as a rescue therapy. The Irish cohort, despite largely classical phenotypes, achieved good outcomes in the NBS era, underlining the importance of early diagnosis and skilled multidisciplinary team management.

中文翻译：

枫糖浆尿病：爱尔兰共和国新生儿血斑筛查四年后筛查人群的临床结果、代谢控制和基因型

自 1972 年以来，爱尔兰已通过新生儿血斑筛查 (NBS) 检测出 18 名患者（10 名女性/8 名男性）患有新生儿发病枫糖浆尿病 (MSUD)。根据收集数据时的临床结果，将患者分为三个组，包括发育、临床和 IQ 数据。第四组包括两名儿童早期死亡；第三名患者成年后死亡。我们提供神经影像学和脑电图以及临床和生化数据。MSUD（1972-2018 年）的发生率为 147975 分之一。 15/18 名患者存活且功能基本正常（只有表现最差的集群超出其全面智商的单一 SD），取得了总体良好的临床结果. 分子遗传分析揭示了迄今未报道的基因型，BCKDHA和DBT一个家庭的基因。治疗基于早期实施紧急治疗、饮食、密切监测，甚至在急性代谢失代偿的情况下进行透析。血浆亮氨酸≥400 μmol/L（超出治疗范围）在婴儿期或青春期更常见，可能是由于感染、激素变化或不依从所致。儿童在儿童早期代谢失代偿期间需要仔细管理，这代表了我们队列中的一个关键风险期。高水平的代谢控制可以通过饮食和早期实施“病假”制度来实现，在某些情况下，透析作为一种抢救疗法。爱尔兰队列尽管主要是经典表型，但在 NBS 时代取得了良好的成果，

更新日期：2020-12-09

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