A Rare Occurrence: Cirrhosis Due to Glycogen Storage Disease IXc

Introduction: Glycogen storage disease (GSD) is a rare disorder characterized by an inability to metabolize glycogen. GSD IXc is an autosomal recessive disease that affects the PHKG2 gene leading to a deficiency of the enzyme phosphorylase kinase. Here, we describe a unique case of cirrhosis due to GSD IXc with a novel mutation in the PHKG2 gene (c.98G >T, p.Gly33Val). Case Description/Methods: A 13-year-old male presented with abdominal distention, recurrent hypoglycemia, and self-resolving jaundice. Clinical examination revealed growth retardation and hepatosplenomegaly. Blood work revealed anemia, thrombocytopenia, elevated aspartate and alanine transaminase levels, and raised plasma cholesterol and triglycerides. Ultrasound showed an enlarged liver with surface irregularity, splenomegaly, and a dilated portal vein. Etiological work-up for cirrhosis was positive for hepatitis B (HBV) surface antigen (HBsAg) and antibodies for HBV core and envelope antigens (anti HBc and anti HBe) but an undetectable HBV DNA level. HBV was considered to be an unlikely cause of cirrhosis due to the young age of the patient, hence further metabolic and genetic work-up was done. Tests for Wilson’s and autoimmune liver disease were negative. A liver biopsy revealed a distorted lobular architecture with nodules, thin septae, and portal fibrosis. Hepatocytes showed marked swelling and pyknotic nuclei, and negative HBsAg immunostaining. Molecular analysis revealed a novel mutation in exon 3 of the PHKG2 gene (c.98G >T, p.Gly33Val). The patient was diagnosed with cirrhosis due to GSD IXc and inactive chronic hepatitis B. His symptoms resolved with an optimized diet of corn starch, high-protein, and vitamin supplementation. The importance of liver transplantation was also discussed with the family. Discussion: GSD presents with developmental delay, hepatomegaly, hypoglycemia, ketosis, and hyperlipidemia. GSD IXc is a more common cause of cirrhosis than the other subtypes of GSD IX. Cases of GSD IXc have been reported in the literature but not in concurrence with HBV. In India, perinatal transmission of HBV is common; however, it is more likely to cause cirrhosis in adulthood. Hence, GSD IXc is considered the main etiology of cirrhosis here. This PHKG2 mutation variant has not been identified before. This case highlights that the diagnosis can often be challenging due to the non-specific presentation, but molecular analysis can help in confirming the subtype of GSD and in the timely initiation of treatment.