Elevated oxysterol and N-palmitoyl-O-phosphocholineserine levels in congenital disorders of glycosylation

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-(3 beta,5 alpha,6 beta-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.

Automated summary

Congenital disorders of glycosylation (CDG) and Niemann-Pick type C (NPC) disease are metabolic errors that can present with severe liver disease and other symptoms. Plasma bile acid and N-palmitoyl-O-phosphocholineserine (PPCS) are biomarkers that can be used for screening NPC. In this study, an infant with ATP6AP1-CDG was found to have elevated oxysterols and bile acid, mimicking NPC. Further investigation showed elevated PPCS in patients with ATP6AP1-, ALG1-, ALG8-, and PMM2-CDG, but not the bile acid derivative TCG. These findings emphasize the importance of considering CDG as a differential diagnosis in children with early-onset liver disease and elevated bile acid or PPCS to prevent delayed diagnosis and treatment.