Office of the Clinical Director, NICHD, NIH, Bethesda, Maryland, USA.
Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, USA.
J Inherit Metab Dis. 2023 Mar;46(2):326-334. doi: 10.1002/jimd.12595. Epub 2023 Feb 3.
Congenital disorders of glycosylation (CDG) and Niemann-Pick type C (NPC) disease are inborn errors of metabolism that can both present with infantile-onset severe liver disease and other multisystemic manifestations. Plasma bile acid and N-palmitoyl-O-phosphocholineserine (PPCS) are screening biomarkers with proposed improved sensitivity and specificity for NPC. We report an infant with ATP6AP1-CDG who presented with cholestatic liver failure and elevated plasma oxysterols and bile acid, mimicking NPC clinically and biochemically. On further investigation, PPCS, but not the bile acid derivative N-(3β,5α,6β-trihydroxy-cholan-24-oyl) glycine (TCG), were elevated in plasma samples from individuals with ATP6AP1-, ALG1-, ALG8-, and PMM2-CDG. These findings highlight the importance of keeping CDG within the diagnostic differential when evaluating children with early onset severe liver disease and elevated bile acid or PPCS to prevent delayed diagnosis and treatment.
先天性糖基化障碍 (CDG) 和尼曼-匹克 C 型 (NPC) 疾病都是先天性代谢缺陷，均可导致婴儿期起病的严重肝脏疾病和其他多系统表现。血浆胆汁酸和 N-棕榈酰-O-磷酸胆碱（PPCS）是 NPC 的筛查生物标志物，其敏感性和特异性均有所提高。我们报告了一例 ATP6AP1-CDG 婴儿，其表现为胆汁淤积性肝功能衰竭，血浆氧化固醇和胆汁酸升高，临床上和生化上均类似于 NPC。进一步研究发现，ATP6AP1、ALG1、ALG8 和 PMM2-CDG 患者的血浆样本中 PPCS 升高，而不是胆汁酸衍生物 N-(3β,5α,6β-三羟基-胆烷-24-酰基)甘氨酸 (TCG)。这些发现强调了在评估具有早发性严重肝脏疾病和胆汁酸或 PPCS 升高的儿童时，将 CDG 纳入鉴别诊断的重要性，以避免诊断和治疗的延误。
