THU241 Novel PPARG Pathogenic Gene Variant In Newly Diagnosed Familial Partial Lipodystrophy With Childhood Onset

Abstract

Abstract Disclosure: E.K. Chang: None. K. Greve: None. L. Escobar: None. Background: Familial partial lipodystrophy (FPL) is characterized by progressive, selective body fat loss and is often associated with various metabolic complications including insulin resistance. In particular, FPL Type 3 due to PPARG (peroxisome proliferator-activated receptor gamma) mutations is a very rare subtype with a prevalence of less than 1 per 1,000,000 people overall. This case report describes a clinical case of a child presenting with genetic testing revealing a novel PPARG pathogenic gene variant. Clinical Case: A 9 year old female with history of adoption and unknown family history presented with severe abdominal pain and intractable emesis in the setting of COVID19 infection. Her hospital CT scan of the abdomen was remarkable for pancreatitis and hepatosplenomegaly. Glucose was elevated at 356 mg/dL with normal liver function tests. HgA1c was 11%. Triglycerides were above 4425 mg/dL. Her overall clinical picture was consistent with new onset diabetes mellitus and acute pancreatitis. Physical exam was notable for xanthomatosis and acanthosis nigricans. She was later noted to have partial subcutaneous fat loss of the upper and lower extremities, with preserved fat in the face, neck, and truncal region. She was initiated on insulin therapy and discharged to home once symptomatically improved from her pancreatitis with downtrending triglycerides to less than 450 mg/dL. Her diabetes autoantibodies (Glutamic acid decarboxylase, Islet Antigen-2, Zinc transporter 8 antibodies) resulted as normal, and she was able to discontinue insulin with HgA1c trending down to 4.8% within 4 months of hospital discharge. She underwent whole exome sequencing per recommendation of her lipid specialist and geneticist, which identified a likely pathogenic, previously undescribed variant of PPARG: c.1050_1054dup, p.(Glu352Alafs*12) and a variant of uncertain significance for MC4R: c.409A>G, p.(Ile137Val). This particular variant of PPARG represents a frameshift mutation, resulting in a premature stop codon, likely leading to a loss of normal PPARG function. PPARG mutations are specific to FPL Type 3, which is reportedly associated with atypical fat distribution, diabetes mellitus, hypertriglyceridemia, hypertension, and pancreatitis, consistent with many features of this case. Conclusion: This is the first case to describe the unique PPARG variant c.1050_1054dup, p.(Glu352Alafs*12) which is associated with FPL Type 3. This child's clinical course and evaluation can help with identifying affected individuals of this very rare type of FPL. Presentation: Thursday, June 15, 2023