Natural history of propionic acidemia in the Amish population.
Natural history of propionic acidemia in the Amish population.
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DOI：
10.1016/j.ymgmr.2022.100936
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发表时间：
2022-12
影响因子：
1.9
通讯作者：
Ghaloul-Gonzalez, Lina
中科院分区：
文献类型：
--
作者：
Ehrenberg, Sarah;Vockley, Catherine Walsh;Heiman, Paige;Ammous, Zineb;Wenger, Olivia;Vockley, Jerry;Ghaloul-Gonzalez, Lina
在Amish中，丙酸血症（PA）是由PCCB基因中的纯合致病性变体（c.1606A>G; p.Asn536Asp）引起的。阿米什患者可以有边界或正常的新生儿筛查（NBS）结果和症状可以在任何时候从幼儿期到中年。在非阿米什人人群中，PA的早期诊断和治疗可改善患者结局。在这里，我们提供了来自三个不同的医疗中心的阿米什人诊断为PA的患者的回顾性图表审查的数据，以记录其在阿米什人的自然史，并确定治疗对该人群结局的影响。共有38例患者入组本研究，平均当前年龄为19.9岁（范围4岁-45岁），57.9%为男性。14例患者（36.8%）被诊断为新生儿筛查（NBS）阳性，而24例患者（63.2%）的NBS为阴性或不确定或在其病历中没有NBS记录。这24例患者是在家庭成员被诊断为PA（14例; 58.3%）、因代谢性酸中毒住院治疗（5例; 20.8%）、因癫痫发作住院治疗（3例; 12.5%）或通过脐带血（2例; 8.3%）后通过筛查确诊的。大多数患者接受限制蛋白质饮食（32; 84.2%），包括代谢配方奶粉（29; 76.3%）。大多数接受肉毒碱（35; 92.1%）、生物素（2; 76.3%）和/或辅酶Q10（16; 42.1%）治疗。然而，患者之间的治疗依从性差异很大，据报道，7例（24.1%）患者未依从代谢配方。心肌病是最常见的结果（22; 63.2%），其次是发育迟缓/智力残疾（15; 39.5%）、QT间期延长（14; 36.8%）、癫痫发作（12; 31.6%）、发育不良（4; 10.5%）和基底节卒中（3; 7.9%）。对于那些通过NBS诊断并早期进行饮食和补充管理的患者，尤其是心肌病患者，结果没有明显差异。然而，这是一项有限的回顾性观察性研究。应进行一项前瞻性研究，严格记录治疗依从性，并对心肌病和长QT间期进行普遍筛查，以更好地研究早期发现和治疗的影响。其他治疗选择，如肝移植和未来的治疗，如mRNA或基因治疗，应探讨在这一人群。
Propionic acidemia (PA) in the Amish is caused by a homozygous pathogenic variant (c.1606A>G; p.Asn536Asp) in the PCCB gene. Amish patients can have borderline or normal newborn screening (NBS) results and symptoms can present at any time from early childhood to mid-adulthood. Early diagnosis and initiation of treatment for PA in the non-Amish population improves patient outcomes. Here, we present data from a retrospective chart review of Amish patients diagnosed with PA from three different medical centers in order to document its natural history in the Amish and determine the influence of treatment on outcomes in this population. A total of 38 patients with average current age 19.9 years (range 4y-45y), 57.9% males, were enrolled in the study. Fourteen patients (36.8%) were diagnosed with a positive newborn screening (NBS) while 24 patients (63.2%) had negative or inconclusive NBS or had no record of NBS in their charts. These 24 patients were diagnosed by screening after a family member was diagnosed with PA (14; 58.3%), following a hospitalization for metabolic acidosis (5; 20.8%), hospitalization for seizures (3; 12.5%) or via cord blood (2; 8.3%). The majority of patients were prescribed a protein restricted diet (32; 84.2%), including metabolic formula (29; 76.3%). Most were treated with carnitine (35; 92.1%), biotin (2; 76.3%) and/or Coenzyme Q10 (16; 42.1%). However, treatment adherence varied widely among patients, with 7 (24.1%) of the patients prescribed metabolic formula reportedly nonadherent. Cardiomyopathy was the most prevalent finding (22; 63.2%), followed by developmental delay/intellectual disability (15; 39.5%), long QT (14; 36.8%), seizures (12; 31.6%), failure to thrive (4; 10.5%), and basal ganglia strokes (3; 7.9%). No difference in outcome was obvious for those diagnosed by NBS and treated early with dietary and supplement management, especially for cardiomyopathy. However, this is a limited retrospective observational study. A prospective study with strict documentation of treatment adherence and universal screening for cardiomyopathy and long QT should be conducted to better study the impact of early detection and treatment. Additional treatment options such as liver transplantation and future therapies such as mRNA or gene therapy should be explored in this population.
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影响因子：
3.5
作者：
Malvagia S;Forni G;Ombrone D;la Marca G
通讯作者：
la Marca G
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通讯作者：
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作者：
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通讯作者：
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