Abnormal liver function tests are frequently detected in routine laboratory work. The differential diagnosis is broad and further evaluation is required to identify and treat the underlying cause. We present a patient with abnormal liver function tests who was found to have a unique genetic makeup.
A 68-year-old female patient presented with jaundice and dark urine for 3 months. Past medical history was significant for paroxysmal atrial fibrillation and nephrolithiasis. Past surgical history and family history were insignificant. Home medications included aspirin and atenolol. She used alcohol socially and denied IV drug use. Review of systems was unremarkable. On physical exam, the patient was diffusely jaundiced and had scleral icterus. Vital signs were within normal limits. Abdominal exam showed a soft, non-tender, and non-distended abdomen without organomegaly. Skin exam was significant for multiple spider angiomas. She had elevated AST of 518 U/L, ALT of 246 U/L, alkaline phosphatase of 185 U/L, total bilirubin of 9.5 mg/dL, and direct bilirubin of 4.5 mg/dL. Workup was negative for viral hepatitis, Wilson’s disease, autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. She had elevated Ferritin of 3547 ng/mL and iron saturation of 83%. MRI showed features of intrinsic liver disease without a focal mass. Next, upper endoscopy revealed Grade 1 esophageal varices. Subsequent liver biopsy revealed cirrhosis and increased iron stores. The patient underwent genetic testing for hemochromatosis and alpha-1 antitrypsin deficiency. She had a heterozygous C282Y mutation of the HFE gene. In addition, she had a heterozygous PI*MS mutation of SERPINA1 - the gene that codes for alpha-1 antitrypsin. The patient experienced a slow improvement in her abnormal labs over a period of a few months.
Hereditary hemochromatosis and alpha-1 antitrypsin deficiency are inherited conditions that result in liver damage and eventually liver cirrhosis. Our patient was heterogenous for the HFE gene and developed iron overload on liver biopsy. She was also heterozygous for PI*MS, a less common mutation for SERPINA1 that causes isolated lung disease. Therefore, we can conclude that our patient’s condition was primarily related to iron overload as a result of a mutated HFE gene.