S5477 A Rare Cause of Metabolic Steatohepatitis: Diagnosis and Management of Familial Hypobetalipoproteinemia

Introduction: We report an usual case of a patient presenting with abnormal liver chemistries leading to the diagnosis of familial hypobetalipoproteinemia (FHBL). Case Description/Methods: A 21-year old man presents to the clinic following blood work showing elevated aspartate aminotransferase (AST) of 80 U/L, and alanine aminotransferase (ALT) of 178 U/L, followed by a second set of results showing AST of 111 U/L and ALT of 207 U/L. In addition, the lipid panel shows a low LDL of 25 mg/dL. Abdominal ultrasound shows an echogenic liver, and FibroScan results include normal stiffness score of 6.7 kPa, with a high controlled attenuation parameter score reflecting steatosis. Family history includes his mother treated for metabolic steatotic liver disease and his brother with a similar presentation of abnormal liver chemistry and low LDL with a diagnosis of FHBL. Patient has no gastrointestinal complaints at the time of the visit, but has a prior history of gastroesophageal reflux. Review of medications and examination were unrevealing. Patient has a low ceruloplasmin, but 24-hour urine copper is normal. Given young age and clinical presentation, the patient is referred for genetic evaluation. Genetic testing shows heterozygous loss of function of APOB gene, causing FHBL characterized by his low LCL-C and apoB100. Additional abnormalities include CDKN2B-AS1 gene relating to endothelial dysfunction, and FTO and MC4R genes linked to obesity. The rest of the family is recommended for genetic counseling. The patient was recommended to initiate low dose vitamin E 400 IU per day. Most recent laboratory testing shows improvement of liver enzymes, including a decrease in AST from 40 IU/L to 29 IU/L and ALT from 104 IU/L to 49 IU/L. Discussion: FHBL is an autosomal codominant genetic disorder defined by a decreased or absence of Apolipoprotein B lipoproteins characterized by low triglycerides, ApoB, and LDL levels. The literature shows 2 distinct genotypes of FHBL, heterozygotes and homozygotes with varying symptoms and severities. Homozygotes with APOB-related familial hypobetalipoproteinemia present ophthalmological, gastrointestinal and neurological complications which can arise from childhood to adulthood. Heterozygotes are commonly asymptomatic and may present with mild liver dysfunction and hepatic steatosis. Hepatomegaly and hepatic steatosis can occur due to the inability of hepatocytes to secrete very low density lipoprotein. Monitoring includes regular lipid monitoring and liver function tests.