ESPE Abstracts

Background: Congenital Generalized Lipodystrophy (CGL) is a rare autosomal recessive disease. The prevalence has been reported to be 1 in 10million with around 500 cases worldwide. The absence of functional adipocytes results in storage of lipids in other tissues, including muscle & liver. The diagnosis of CGL is based on clinical data; however, there is phenotypic heterogeneity. Metreleptin injections cause decreased appetite & is beneficial in lowering triglycerides (TG), liver enzymes, & better glycemic control. Unfortunately, it is not available in Egypt. We hereby report 2 cases diagnosed with CGL, and the challenges faced in their management in the absence of metreleptin.

Case 1: A 13-year-old girl born to non-consanguineous parents. Her parents noticed facial dysmorphism & loss of subcutaneous fat. At age 8 years, she had recurrent attacks of abdominal pain & her U/S showed bilateral ovarian cyst torsion. At age 9 years, she was diagnosed clinically with CGL (hepatomegaly, acanthosis nigricans, acromegaloid features & muscular appearance). Her TG, fasting blood sugar, & liver functions were normal. After skipping follow up for 2 years, xanthomas were observed on the upper & lower limbs with severe hyperTG. She was also diagnosed with DM with HbA1c 13% & high C-peptide. She was discharged on dietary advice, insulin, metformin, omega 3, fenofibrates & statins. At age 12 years, she complained of severe abdominal pain with shooting lipase & admitted with acute pancreatitis due to hyperTG. She continued to have recurrent attacks of pancreatitis-even though antilipidemic treatment was maximized. Her last HbA1C is 9.6% on insulin requirement 5 U/Kg/day & she never had DKA.

Case 2: A 12-year-old girl born SGA to consanguineous parents. She was diagnosed with CGL at the age of 4 months with typical facial features, hepatomegaly, hirsutism, hyperTG, & elevated liver enzymes. Her liver biopsy showed moderate macrovesicular steatosis & cirrhosis. She was given fenofibrates. At 4.5 years, she had advanced bone age, height +2.6SD, & developed precocious puberty. She complained of polyuria, polydipsia at 7 years & was diagnosed with DM (HOMA-IR 8.1%, HbA1c 8.4%),& started metformin. Her last HbA1c is 6.9% on only metformin 2000 mg/day & has normal TG level. She has never had attacks of pancreatitis or DKA. However, she has liver cirrhosis & is on liver support.

Conclusions: CGL is a rare & severe disease that can manifest with DM at any age. Patients can be diagnosed clinically as their phenotypic characteristics are unique; however, different presentations and severity exist. Without metreleptin, challenges are faced & treatment should be individualized.