Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Dis Model Mech. 2023 Nov 1;16(11). doi: 10.1242/dmm.050233. Epub 2023 Nov 23.
Amino acids are organic molecules that serve as basic substrates for protein synthesis and have additional key roles in a diverse array of cellular functions, including cell signaling, gene expression, energy production and molecular biosynthesis. Genetic defects in the synthesis, catabolism or transport of amino acids underlie a diverse class of diseases known as inborn errors of amino acid metabolism. Individually, these disorders are rare, but collectively, they represent an important group of potentially treatable disorders. In this Clinical Puzzle, we discuss the pathophysiology, clinical features and management of three disorders that showcase the diverse clinical presentations of disorders of amino acid metabolism: phenylketonuria, lysinuric protein intolerance and homocystinuria due to cystathionine β-synthase (CBS) deficiency. Understanding the biochemical perturbations caused by defects in amino acid metabolism will contribute to ongoing development of diagnostic and management strategies aimed at improving the morbidity and mortality associated with this diverse group of disorders.
氨基酸是有机分子，它们作为蛋白质合成的基本底物，并在多种细胞功能中具有额外的关键作用，包括细胞信号转导、基因表达、能量产生和分子生物合成。氨基酸合成、分解代谢或运输的遗传缺陷是一类称为氨基酸代谢先天错误的多种疾病的基础。这些疾病单独发生的情况很少见，但总体而言，它们代表了一组重要的、具有潜在可治疗性的疾病。在这个临床谜题中，我们讨论了三种疾病的病理生理学、临床特征和管理，这些疾病展示了氨基酸代谢紊乱的不同临床表现：苯丙酮尿症、赖氨酸尿蛋白不耐受症和胱硫醚β-合成酶（CBS）缺乏引起的高胱氨酸尿症。了解氨基酸代谢缺陷引起的生化紊乱将有助于不断发展旨在改善与这一组多种疾病相关的发病率和死亡率的诊断和管理策略。
