Agana Marisha, Frueh Julia, Kamboj Manmohan, Patel Dilip R, Kanungo Shibani
Department of Pediatric and Adolescent Medicine, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, MI, USA.
Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA.
Ann Transl Med. 2018 Dec;6(24):469. doi: 10.21037/atm.2018.12.34.
Inborn errors of metabolism (IEMs) are rare genetic or inherited disorders resulting from an enzyme defect in biochemical and metabolic pathways affecting proteins, fats, carbohydrates metabolism or impaired organelle function presenting as complicated medical conditions involving several human organ systems. They involve great complexity of the underlying pathophysiology, biochemical workup, and molecular analysis, and have complicated therapeutic options for management. Age of presentation can vary from infancy to adolescence with the more severe forms appearing in early childhood accompanied by significant morbidity and mortality. The understanding of these complex disorders requires special in-depth training, American Board of Medical Genetics and Genomics (ABMGG) certification and experience. Most primary care physicians (PCPs) are reluctant to deal with IEM due to unfamiliarity and rarity of such conditions compounded by prompt progression to crisis situations along with paucity of time involved in dealing with such complex disorders. While there are biochemical geneticists aka metabolic specialists' expertise available, mostly in larger academic medical centers, with expertise to deal with these rare complex issues, their initial clinical presentation in most newborns, children, adolescents or adults including asymptomatic positive newborn screen (NBS), occur in the out-patient PCP settings. Therefore, it is important that PCPs' comfort to recognize early signs and symptoms is important to initiate appropriate diagnostic and therapeutic interventions, and be able to make appropriate referrals. The following article reviews common IEM clinical presentations for a robust diagnostic differential and discuss evaluation and management approaches of patients with known or suspected IEM.
先天性代谢缺陷（IEMs）是罕见的遗传或遗传性疾病，由影响蛋白质、脂肪、碳水化合物代谢的生化和代谢途径中的酶缺陷或细胞器功能受损引起，表现为涉及多个人体器官系统的复杂病症。它们涉及潜在病理生理学、生化检查和分子分析的极大复杂性，并且有复杂的治疗管理选择。发病年龄从婴儿期到青春期不等，较严重的形式出现在幼儿期，伴有显著的发病率和死亡率。对这些复杂疾病的理解需要特殊的深入培训、美国医学遗传学与基因组学委员会（ABMGG）认证和经验。大多数初级保健医生（PCP）由于不熟悉此类病症且其罕见性，再加上病情迅速发展到危急情况以及处理此类复杂疾病所需时间有限，而不愿处理先天性代谢缺陷。虽然有生化遗传学家，也就是代谢专家，他们大多在较大的学术医疗中心，具备处理这些罕见复杂问题的专业知识，但这些疾病在大多数新生儿、儿童、青少年或成人中的初始临床表现，包括无症状的新生儿筛查阳性（NBS），都发生在门诊初级保健医生的诊疗环境中。因此，初级保健医生能够识别早期体征和症状对于启动适当的诊断和治疗干预并能够进行适当转诊非常重要。以下文章回顾了常见的先天性代谢缺陷临床症状以进行有力的鉴别诊断，并讨论已知或疑似先天性代谢缺陷患者的评估和管理方法。
