Abstract Introduction Lipodystrophy is a rare and heterogeneous disorder characterized by selective loss or abnormal redistribution of adipose tissue, leading to metabolic complications such as insulin resistance, diabetes mellitus, hepatic steatosis, and dyslipidemia. Lipodystrophy is divided into 4 main groups: congenital generalized lipodystrophy (CGL), familial partial lipodystrophy (FPLD), acquired generalized lipodystrophy (AGL), and acquired partial lipodystrophy (APL). FPLD is caused by mutations is genes regulating adipocyte function and lipid metabolism, with six subtypes identified to date. Among these, type 6 (FPLD6) results from inactivating mutation in the LIPE gene, which encodes hormone-sensitive lipase (HSL). Here, we present a very rare case of autosomal recessive familial partial lipodystrophy type 6. Clinical Case A 34-year-old female was referred for evaluation of suspected Cushing’s syndrome. She was receiving hormone replacement therapy for primary ovarian insufficiency and had no other known medical conditions. She had gestational diabetes during her second pregnancy, managed with diet alone. Over three years she gained 29 kg (BMI 35.2 kg/m²). Family history revealed parental consanguinity. Physical examination revealed characteristic cushingoid features including a prominent buffalo hump, supraclavicular fat pads, and centripetal obesity. She had fat accumulation in the upper body while subcutaneous fat was markedly reduced in the extremities and breasts (Figure 1). Acanthosis nigricans was noted in the axillary and cervical regions. Additionally, she had undergone a cosmetic liposuction procedure targeting the deltoid and occipital regions. Low-dose dexamethasone testing excluded Cushing’s syndrome. Oral glucose tolerance test indicated insulin resistance; triglycerides were elevated, while leptin was normal. Laboratory results are summarized in Table 1. Whole-body DXA demonstrated markedly reduced fat mass in the upper and lower extremities, with central fat accumulation. This distribution was compatible with partial lipodystrophy. FibroScan revealed advanced hepatic steatosis (S3) without fibrosis (F0), consistent with nonalcoholic fatty liver disease (NAFLD). Genetic analysis identified a homozygous pathogenic LIPE gene variant (c.2182GA), confirming the diagnosis of autosomal recessive familial partial lipodystrophy type 6. Treatment with metformin, SGLT-2 inhibitor, and fenofibrate was initiated, alongside lifestyle modification and genetic counseling. Conclusion FPLD6 is a very rare subtype of familial partial lipodystrophy. Unlike other subtypes, it is caused by LIPE mutations leading to defective lipolysis, and typically presents in adulthood rather than early life. It is further characterized by severe insulin resistance, dyslipidemia, and hepatic steatosis. In addition, the presence of subcutaneous lipomas distinguishes FPLD6 from other many forms and may lead to diagnostic confusion with multiple lipomatosis.Figure 1:a.Sagittal magnetic resonance imaging (MRI) of the neck and cervical spine region demonstrating abnormal fat distribution consistent with partial lipodystrophy b.Dual-energy X-ray absorptiometry (DEXA) scan demonstrating body composition c.Posterior view of the trunk showing loss of peripheral fat and abnormal fat deposition in the upper body Table 1:Biochemical parameters of the patientIR: insulin resistance
Öktem et al. (Thu,) studied this question.