Authors M. SURMONT (1), C. SALEM (2), C. DELBAEN (3), V. LUCIDI (4), J. MULKAY (2), T. SERSTÉ (2) / [1] CHU Saint-Pierre, Brussels, Belgium, hepato-gastroenterologie, [2] CHU Saint-Pierre, Brussels, Belgium, hepato-gastroenterology, [3] CHU Saint-Pierre, Brussels, Belgium, hepato-gastroenterology, [4] Erasme Hospital, Brussels, Belgium, Liver transplant unit Background Maturity-Onset Diabetes of the Young type 3 (MODY 3) is caused by several heterozygous germline mutations in the Hepatocyte Nuclear Factor 1alpha (HNF 1A) gene. The inactivation of this specific gene has been identified in a subgroup of hepatocellular adenomas: the so-called HNF 1A-mutated hepatocellular adenomas (H HCA). The clinical entity characterized by ten or more hepatocellular adenomas is called liver adenomatosis. It is especially rare to identify liver adenomatosis in individuals with MODY 3. In these patients, the genetic testing is particularly interesting. Case presentation We describe the case of a genetically-proven HNF 1A mutation occurring in a young woman suffering from MODY 3 and liver adenomatosis. She was diagnosed with early-onset non-insulin-dependent diabetes mellitus at the age of seven. Two of her three brothers were diabetic as well. Genetic evaluation was performed at the age of nineteen: testing on blood sample revealed a heterozygous germline mutation of HNF 1A, c.827C>A (p.Ala276Asp) in exon 4, and the diagnose of MODY 3 was established. Subsequently, the patient was lost to follow-up in her referential centre. At the age of 27 (and four months post-partum), she was admitted to the hospital for abdominal pain located at the right upper quadrant without fever. She had a history of oral contraceptive use and was now treated with subcutaneous insulin. Clinical examination showed no abnormalities. Laboratory testing didn’t disclose abnormalities. Computed tomography revealed a homogenous liver parenchyma with numerous masses of different sizes. Retrospectively, multiple small lesions were seen on computed tomography five years before. Magnetic resonance imaging showed numerous (> ten) fat-containing nodules disseminated in the liver parenchyma. The largest lesion was situated in segment V, had a size of 64 x 44 mm with a heterogeneous aspect and had a marked hypervascular component. The use of a hepatobiliary contrast agent (Primovist®) didn’t disclose hypercaptation of the lesions. The diagnosis of steatotic adenomatosis of the liver and H HCA was highly suspected. Percutaneous biopsy of the dominant liver lesion showed benign hepatocellular proliferation without evidence of bile ducts in the tumor; this was consistent with steatotic adenoma of the liver. Because of the volume of the largest lesion and the symptomatic disease, bisegmentectomy V-VI was performed. Postoperative excisional macro-biopsies showed typical steatotic adenomas without dysplasia. Genetic analysis of the DNA extraction from this adenoma revealed a c.827C>A heterozygous mutation in exon 4 (mean coverage >1000, in 52.1% of the analysis). This mutation was identical to the HNF 1A germline mutation, previously identified. The mutation c.827C>A of the HNF 1A gene has been described in MODY 3 in recent literature, but has never been identified in H HCA. Conclusions The association between HNF 1A mutation and H HCA is well described. In this exceptional case, a young woman previously known with a c.827C>A (p.Ala276Asp) mutation of HNF 1A and suffering from MODY 3 was admitted with a symptomatic liver adenomatosis. Genetic analysis of the DNA extracted from the largest adenoma confirmed the same HNF 1A mutation. This clinical case is particularly interesting: first, because it highlights a specific mutation in HNF 1A, previously described in MODY 3 but never identified in liver adenomatosis. Second, this case underlines the importance of surveillance of liver adenomatosis in MODY 3 patients aiming to prevent life threatening complications, such as haemorrhage and malignant transformation. Currently, screening and follow-up of H HCA are not included in guidelines for the management of MODY 3 patients.
