S3275 A Peculiar Case of Limb-Girdle Muscular Dystrophy Masquerading as Elevated Transaminases

Abstract

Introduction: A disproportional elevation in aspartate transaminase (AST) and alanine transaminase (ALT) is considered a marker of hepatocellular injury. Guidance on the work up of chronically elevated liver chemistry suggests an algorithmic approach to testing of common causes of liver injury based on the degree of elevation and even mentions consideration of nonhepatic etiologies such as skeletal muscle damage. We present a unique case of asymptomatic elevation in liver chemistries as the herald finding in a patient with limb-girdle muscular dystrophy (LGMD). Case Description/Methods: Our patient is a 19-year-old adopted male who was referred to outpatient gastroenterology clinic for asymptomatic elevation in transaminases. AST was 133 IU/L and ALT was 223 IU/L. Total bilirubin and alkaline phosphatase were normal. He denied alcohol use, prescribed medications, herbal supplements, or weightlifting supplements. BMI was normal. Workup for viral hepatitis, hemochromatosis, autoimmune hepatitis, Wilson’s disease, alpha-1 antitrypsin, celiac disease, and thyroid disease were normal. Liver biopsy revealed reticulin collapse with complete regeneration without inflammation. Subsequent follow-up over years demonstrated persistently elevated but stable elevations. At the age of 24, he began to endorse proximal lower extremity muscle pain and weakness. Creatine kinase (CK) was elevated at 11,937 U/L; aldolase was elevated at 31.4 U/L; myositis workup was normal. Right thigh biopsy revealed a myopathic process. Genetic testing confirmed mutation in the CAPN3 gene consistent with calpainopathy, a subtype of LGMD. Discussion: LGMD is a rare, genetic disorder resulting in loss of ambulation within 20 years after disease onset. Concurrent liver disease is rare in LGMD, but elevations in transaminases can be found because of severe elevations in CK. Our patient was found to have calpainopathy, a subtype associated with a recessive mutation in the CAPN3 gene. Our case demonstrates that beyond the recommended algorithmic evaluation of abnormal liver chemistries, inconclusive evaluation of abnormal liver chemistries in children and young adults should include a CK level to further investigate nonhepatic causes, specifically a myopathic process. Although there is no cure for LGMD, interventions focused on muscle conditioning are more beneficial with early detection to mitigate the devastating effects of this disorder.