JIMD Rep. 2025 Nov 24;66(6):e70050. doi: 10.1002/jmd2.70050. eCollection 2025 Nov.
ABSTRACT
Pompe disease (PD) is an autosomal recessive disorder caused by pathogenic variants in GAA, resulting in acid alpha-glucosidase (GAA) deficiency and lysosomal glycogen accumulation. PD is classified into infantile-onset (IOPD), characterized by cardiomyopathy and death within the first year if untreated, and late-onset (LOPD), which presents with gradual muscle weakness at variable ages. Incidentally elevated transaminase levels are common in LOPD and reflect muscle injury rather than liver damage. Creatine kinase (CK) levels are often elevated too, further indicating a myopathic origin. However, these elevated transaminases may be misattributed to liver disease, prompting a liver biopsy. Three charts of patients who underwent liver biopsies prior to a LOPD diagnosis were reviewed, including clinical presentations and diagnostic workups. Liver histology from these biopsies was evaluated and compared to liver pathology in a GAA knockout mouse model. All cases had elevated transaminases and underwent a liver biopsy. One biopsy was normal, while two showed non-specific hepatocyte glycogen accumulation. In all cases, aspartate transaminase (AST) levels were higher than alanine transaminase (ALT) levels and CK levels were elevated. Enzyme testing demonstrated GAA deficiency, and genetic testing identified biallelic variants in GAA, confirming the diagnosis. These cases highlight the importance of meticulous phenotyping before liver biopsy. A muscle origin should be considered when AST:ALT > 1 with elevated CK levels. Neuromuscular gene panels and GAA enzyme testing offer a non-invasive diagnostic approach in LOPD. Notably, even when glycogen accumulation is observed in the liver histologically, liver disease is not associated with PD.
PMID:41293654 | PMC:PMC12643788 | DOI:10.1002/jmd2.70050
