Chronic Nausea and Vomiting and Accelerated Progression to Cirrhosis in a Patient with a Mitochondrial Enzyme Deficiency

Abstract

Purpose: Defects in fatty-acid oxidation are generally seen in the pediatric population, characterized by metabolic decompensation during fasting, hypoglycemia, vomiting, encephalopathy, and severe skeletal muscle, heart, and liver dysfunction. The associated mitochondrial deficiencies often lead to microvesicular and macrovesicular hepatic steatosis with subsequent liver failure. Early infant death is common; hence, these disorders are rarely seen in the adult population. We present a rare case of an adult with a mitochondrial enzyme disorder and concurrent hepatitis C, with subsequent rapid acceleration to cirrhosis. Case Report: A 35 year old male was referred to us after work-up of a 5 year history of persistent nausea and vomiting revealed elevated transaminases and hepatitis C, genotype 2. Other symptoms included severe myalgias, episodic confusion, and fasting hypoglycemia. Laboratory studies revealed the following: Total bilirubin 0.8 mg/dl, Alkaline phosphatase 169 U/L, AST 529 U/L, ALT 906 U/L, INR 0.9, glucose 61 mg/dl, aldolase 34.9 IU/L and LDH 329 IU/L. Serologic studies for additional liver disorders were unremarkable. Liver biopsy revealed chronic hepatitis C, grade 2, stage 2, and steatohepatitis. Additional work-up for his symptoms including EGD, colonoscopy, and ultrasound were unremarkable. Metabolic testing revealed reduced carnitine palmitoyl transferase II (CPT II) in cultured skin fibroblasts, consistent with heterozygous CPT II deficiency. He was placed on a low-fat, high carbohydrate diet with some clinical improvement. Interferon therapy for hepatitis C was unsuccessful. He rapidly progressed from stage II fibrosis to cirrhosis within 2 years, subsequently requiring liver transplantation. Conclusion: We present a patient with a rare deficiency of the mitochondrial enzyme CPT II and concurrent hepatitis C, genotype 2, with steatohepatitis, persistent nausea and vomiting, myalgias, fasting hypoglycemia, occasional encephalopathy, and subsequent rapid progression from stage 2 fibrosis to cirrhosis within two years. CPT II is important in mitochondrial fatty acid oxidation, and deficiency generally results in muscle necrosis. It only rarely presents with hepatic decompensation, except with severe deficiencies. Chronic hepatitis C has a variable rate of progression, but can progress to cirrhosis in as long as 20 years. Macrovesicular steatosis is occasionally seen in hepatitis C, but generally in genotype 3 infections. CPT II deficiency was likely the cause of his emesis and may have contributed to the steatosis and rapid progression to cirrhosis. Subclinical mitochondrial enzyme deficiencies should remain in the differential diagnosis for steatosis and for recurrent nausea and vomiting.