Metabolic Syndrome in a Teenager as a Clinical Picture of R482W LMNA Mutation

Metabolic Syndrome (MS) can be diagnosed from the age of 10 years, when the coexistence of abdominal obesity, glucose metabolism disorders, dyslipidemia, and hypertension is observed. A binding part of MS is insulin resistance. Severe insulin resistance may be caused by a mutation in lamin (LMNA) gene. A teenager with MS due to mutation in LMNA gene is presented. A 17.5-yr-old Caucasian girl was admitted to the hospital with the suspicion of diabetes mellitus due to causal blood glucose 393 mg/dl (21.8 mmol/l), without typical diabetic symptoms. Since the age of 13 years she had been presented with excessive weight gain, hirsutism, and oligomenorrhoea. Her family history was positive for diabetes and partial lipodystrophy in three generations. Physical examination revealed abdominal obesity (waist-circumference 86 cm, BMI 27 kg/m2), android/cushingoidal habitus, acanthosis nigricans in axillae and neck, hirsutism, enlarged liver, and pseudohypertrophy of muscles of limbs with partial lipodystrophy. Based on oral glucose tolerance test diabetes was diagnosed (HOMA-IR 14). HbA1c was 9.2% (78 mmol/mol). Diabetes autoantibodies were negative. Lab tests revealed also dyslipidemia (total cholesterol 6.42 mmol/l, triglicerydes 7.42 mmol/l, HDL cholesterol 0.73 mmol/l) and elevated liver enzymes. Ultrasonography revealed steatosis hepatis and polycystic ovaries. Genetic tests confirmed that she is a carrier of heterozygous missense mutation (c.1444C>T; R482W) in the LMNA gene. Lifestyle changes, metformin dosage 500 mg three times a day and ursodeoxycholic acid were introduced as her therapy. After 4 months of this treatment HbA1c levels dropped 5.8% (40 mmol/mol). Moreover an improvement of lipid profile, liver tests and 2 kg body weight loss were observed. Diabetes mellitus as a component of MS in a young obese patient should be diagnosed individually. When other nontypical for diabetes mellitus clinical signs and symptoms exist with positive, multigenerational family history, genetic causes of MS should be taken into consideration.