A tale of two sisters

Abstract

Hereditary haemochromatosis is the most common inherited disorder in white populations, whereas non-alcoholic steatohepatitis (NASH) is becoming the most common reason for referral for investigation of abnormal liver function tests (LFTs). This report describes two sisters, from similar environments, who were referred to the clinic after being found to be C282Y homozygotes and to have abnormal LFTs. One sister had developed features of haemochromatosis and the other had developed NASH. These cases illustrate the potential non-penetrance of HFE gene mutations and the need to investigate abnormal LFTs fully, even when there is a positive genetic test at the outset.T he two sisters both presented to the gastroenterology clinic at a district general hospital. CASE 1ER, a 48 year old woman, was referred to the clinic for the investigation of abnormal LFTs. Her father had died from a hepatoma; he had no previously known liver complaints, but had developed diabetes and a tanned complexion in his last years. After his death, ER investigated his medical history with the help of the internet, and becoming concerned that her father might have died from complications arising from undiagnosed haemochromatosis, consulted her general practitioner.She had no relevant past medical history, was taking no medication and, apart from her father's history, had no risk factors for liver disease. In addition, she had a normal menstrual history.On examination she appeared well. Her body mass index (BMI) was 24 and there were no stigmata of chronic liver disease.Investigations revealed mildly deranged LFTs, with the only abnormalities being an aspartate aminotransferase (AST) of 55 U/litre (normal, , 25) and c glutamyl transpeptidase (cGT) of 57 U/litre (normal, , 50). Autoantibody screening and viral serology were both negative. Both serum ferritin and transferrin saturation were raised at 981 mg/litre (normal range, 18-300) and 73 mg/litre (normal range, 15-45), respectively. Genotyping revealed that she was homozygous for the C282Y mutation of the HFE gene (and wild-type for the H63D mutation). Liver biopsy (fig 1) revealed features in keeping with haemochromatosis; the calculated hepatic iron index was 2.62 mmol/g/year (normal, , 1.9), supporting the overall diagnosis of genetic haemochromatosis. CASE 2CR, a 53 year old woman and elder sister of ER, was subsequently referred to the same clinic. Both sisters had lived on the same street since leaving their childhood home. After being alerted by her sister's problems, she visited her general practitioner and was found to have abnormal LFTs and to be homozygous for the C282Y mutation (and wildtype for the H63D mutation).She had a past history of ischaemic heart disease, type 2 diabetes, hypothyroidism, and osteoarthritis of the hip. Her current medications were aspirin, isosorbide mononitrate, lisinopril, metformin, thyroxine, and dihydrocodeine. She consumed less than 10 units of alcohol each week, had no risk factors for viral hepatitis, and had a normal past menstrual history.On exam...

Fat luck: three siblings requiring liver transplantation for nonalcoholic steatohepatitis

“…1432-2277.2007.00586.x In conjuction with the epidemic of obesity [body mass index (BMI) ‡30kg/m 2 ], nonalcoholic steatohepatitis (NASH), has emerged as the most common cause of liver disease in modern civilization with environmental and inherited factors being implicated [1][2][3][4]. The prevalence of obesity in adults has been increasing continuously (1991: 12.0%; 1998: 17.9%; 2004: >20% in almost all states in the USA) [2].…”