Clinical Case Summary

A 45-year-old man with medical history of hypertension, dyslipidaemia and maturity-onset diabetes of the young type 5 (MODY 5) complicated by retinopathy and nephropathy, under insulin, linagliptin, ramipril, and atorvastatin was referred to Hepatology in 2021, due to elevated liver enzymes spanning four years. The patient was asymptomatic, with no history of blood transfusions, risky behaviours or new medication. Physical examination was normal with a BMI of 24 kg/m². Initial laboratory results revealed AST 78 U/L, ALT 135 U/L, ALP 329 U/L, GGT 266 U/L, total bilirubin 0.8 mg/dL, and HbA1c 8.9%. Metabolic, autoimmune, and infectious causes were excluded due to normal blood tests. Abdominal ultrasound and CT scan displayed no pathological findings. Transient elastography showed normal results (elasticity of 5.1 kPa, controlled attenuation parameter of 169 dB/m with a low median IQR). Due to persistent elevated liver enzymes a liver biopsy was conducted revealing lobular hepatocytes with ballooning, glycogenotic nuclei, minimal steatosis (<1%), and focal minimal granulocytic perisinusoidal inflammation, devoid of fibrosis, iron deposits, or hyaline globules, excluding the most common causes. Biochemical abnormalities were therefore associated with MODY5.
Conclusion: Maturity-onset diabetes of the young (MODY) is a common type of monogenic diabetes with an autosomal dominant inheritance that leads to defects in pancreatic islet cell development. MODY 5 is a subset that accounts for less than 5% of the cases, being caused by a mutation in hepatocyte nuclear factor 1 β (HNF1β) gene, which is a transcription factor expressed in various organs. Involved in the regulation of the expression of liver enzymes, when mutated may result in biochemical abnormalities. There are few reported cases of MODY liver-associated disease, so it should be included in the differential diagnosis of persistently abnormal liver enzymes, particularly in diabetic young patients^1,2.

References

1. Veerareddy S, Reddy S, Barreto M, Vedherey N, Gopalareddy VV. Increased Liver Enzymes: An Under-Recognized Finding in Maturity-Onset Diabetes of the Young Type 5 (MODY 5). ACG Case Rep J. 2023 Oct 3;10(10):e01150.
2. Bala V, Anania FA. Increased liver enzyme levels and HNF-1beta gene mutation. Clin Gastroenterol Hepatol. 2008 Dec;6(12):A26.