LMNA mutations cause a wide range of diseases involving either specific tissues in isolated fashion (cardiac and skeletal muscles, nerve, adipose tissue) or several tissues in a generalized way (premature ageing syndromes…). The cardiac disease is defined by conduction and rhythm disturbances, followed by dilated cardiomyopathy, heart failure, and sudden cardiac death. We report an unusual case of laminopathy revealed by diabetes associated with conduction disturbances related to a not-yet described LMNA mutation. A 36-year old woman was admitted because of hyperglycemia (11 mmol/l) discovered after a 12-kg weight loss. Clinical examination showed a BMI that was still 34 with android repartition, waist acanthosis nigricans, hyperlordosis and short hands. Blood pressure was 130/67 mmHg and heart frequency 40 bpm related to an asymptomatic auriculo-ventricular conduction block requiring pace maker implantation. HbA1c level was 9.4% with mild increase of liver enzymes (ALAT: 64, ASAT 85 UI/l (N<30), cholesterol (2.31 g/l; N<2.0) and triglycerides (2.49 g/l; N<1.5). Blood magnesium level was 15 mg/l (N: 1822). A heterozygous deletion of C 2159 in exon 5 of the LMNA was identified in the propositus but not in eight family members. Nevertheless, family inquiry had shown a history of dyslipidemia and premature sudden death (<45 years old) in the mother who also had a pace-maker, grand-mother who had muscular weakness, and two brothers of this grand-mother. The son of one of them also had a pace-maker since the age of 35. To conclude, this case report shows that cardiac laminopathy may be revealed by diabetes and atypical lipodystrophy, linked to new LMNA mutation. However, suggestive phenotypes in the other family members with absence of the described pathogenic genotype, rise the question of the association with another gene mutation or a role of hypomagnesemia.
03 - 07 May 2008
European Society of Endocrinology