Novel MFN2 compound heterozygote genotype in a patient with multiple symmetric lipomatosis and metabolic dysfunction

Inherited lipodystrophy syndromes are rare disorders of energy metabolism. Patients exhibit adipose tissue atrophy with metabolic dysregulation linked to ectopic fat deposition. Here, we describe the case of a 67-year-old woman presenting with partial adipose tissue atrophy, multiple symmetric lipomatosis, and muscle pseudohypertrophy. Metabolically, she had long-lasting diabetes mellitus with severe insulin resistance and hypertriglyceridemia. She developed hepatomegaly with steatosis, neuropathy, proteinuria, and coronary artery disease. In accordance with an inherited etiology, the patient's family history was positive for lipomatosis and premature heart disease. Targeted sequencing identified a variant in the MFN2 gene, previously linked to lipomatosis and Charcot-Marie-Tooth neuropathy. Copy number variation analysis revealed a novel 5.4 kb duplication in the MFN2 gene. Hence, we describe a novel compound heterozygote MFN2 genotype in this patient, which we believe accounts for her metabolic phenotype. Raising awareness of lipodystrophy syndromes is important because treatment with recombinant leptin, when available, can improve metabolic outcomes.