ESPE Abstracts

Background: Familial partial lipodystrophy type 2 (FPLD2) is a heterogeneous rare disease characterized by selective fat loss, mainly affecting the limbs. It is attributed to LMNA gene, which encodes lamins A and C, structural proteins components of the nuclear lamina. LMNA variants have been previously described with cardiac abnormalities with and without lipodystrophy in FPLD2.

Case description: We describe a 17-year-old girl who is followed in the Endocrine clinic for evaluation of significant acanthosis nigricans on abdominal wall, neck, axillary and inguinal areas; muscular extremities, hirsutism, decreased fat on face, abdomen and extremities. Her BMI was low at 17 kg/m2. BP was elevated. She initially presented at 15 years of age with right ovarian cyst for which she underwent laparoscopic surgery. She had menarche at 11 years, the menses were irregular. Endocrine profile showed normal ACTH, prolactin, LH, FSH, 17 OHP, testosterone levels and thyroid function. Fatty infiltration of the liver was noticed on the sonogram and CT of the abdomen. Elevated ALT 104 U/L (nl < 35), AST 69.8 U/L (nl < 35), consistent with fatty liver. Elevated insulin levels of 218 mcIU/ml, TG levels of 1.56 mmol/L (0.44-1.4) and HbA1c 6.2 %, consistent with prediabetes and insulin resistance. C-peptide was normal at 3.54 ng/ml (1.1-4.4). LDL was low 0.67 mmol/L (0.91-1.91). At 16 yrs. she had ischemic stroke in the left frontal area, confirmed by brain MRI. Thrombotic work up was normal. At 17 yrs. she presented with syncope episode, hypertension, arrhythmias with alternating tachycardia during daytime with severe bradycardia at night. Echocardiogram revealed dilatation of the left ventricle, mitral valve insufficiency. She was diagnosed with dilated cardiomyopathy and conduction defects. A Cardioverter-defibrillator was implanted. She was diagnosed with partial lipodystrophy and treatment with Metreleptin is currently being planned.

Results: She was tested for mutational analysis of the LMNA gene, which causes autosomal dominantly inherited FPLD2. She was found to have a heterozygous pathogenic c.1488+1G>A mutation in the LMNA gene. This variant is listed as "pathogenic" in HGMD mutation database (CS094346) (PubMed ID:20848652,34240052) and ClinVar mutation database.

Conclusion: It is important to evaluate cardiac function in patients with FPLD type 2. This mutation has been reported previously in patients with various lipomusculodystrophies, cardiomyopathies and channelopathies with fatal outcomes. It is imperative for a Paediatric Endocrinologist to recognize that early detection of the cardiac phenotype in FPLD2 can prevent stroke and life-threatening arrhythmias in such cases.