Endocrine Abstracts

Background: Familial partial lipodystrophy type 2 (FPLD2) is an autosomal dominant inherited form of lipodystrophy due to mutation in the LMNA gene on chromosome 1q22. It is characterized by selective loss of subcutaneous adipose tissue from the limbs and trunk, with accumulation of fat in the neck and face, insulin resistance, diabetes mellitus and dyslipidemia.

Objective: To study the clinical features and establish the molecular diagnosis of two subjects with FPLD2.

Subjects and methods: Utilizing next generation sequencing (NGS) we carried out mutational analysis of LMNA gene in a woman and her mother with FPLD2 phenotype.

Results: A 23-year-old lady and her mother were diagnosed to have diabetes mellitus at age 16 and 30 years respectively. Both never had keto-acidosis and required high doses of insulin with suboptimal glycaemic control. They had cushingoid appearance of the face, acanthosis nigricans, minimal fat in the limbs with prominent muscular contours and veins, and hepatomegaly consistent with FPLD2. The subject and her mother had elevated HOMA-IR and hypertriglyceridemia suggestive of insulin resistant diabetes mellitus. Dual-energy X-ray absorptiometry showed relatively increased fat in the head, with decreased fat in the limbs and trunk confirming fat redistribution.

The NGS of LMNA gene showed that the mother and daughter were both heterozygous for a reported c.1444C>T missense mutation¹ which causes the substitution of the Arginine at residue 482 by tryptophan, and was confirmed by Sanger sequencing.

The subjects were started on metformin and insulin therapy was optimized resulting in better glycaemic control.

Conclusions: Clinical suspicion of FPLD2 based on phenotype followed by appropriate biochemical and genetic testing of LMNA gene led to the diagnosis. A clear understanding of the disease process and molecular diagnosis is important to provide appropriate treatment and genetic counseling.

Reference: 1. Nabrdalik et.al. Endokrynol Pol 2013 64 (4) 306–311.