Abstract
Disclosure: V.P. de Souza: None. J.R. Calmon: None. V. Pacheco: None. R.D. Muniz: None. R.B. Muniz: None. C.M. Valerio: None. A.F. Godoy-Matos: None.
Background: Familial partial lipodystrophy (FPLD) is a group of genetic disorders, generally autosomal dominant, caused by heterozygous pathogenic variants, characterized by abnormal distribution of body fat and metabolic complications. We will present a series of three cases of patients from the same family, with involvement of the PPARG variant c.846delC p.Leu283*, associated with type 3 FPLD. Case 1. Index patient, a 17-year-old woman hospitalized with pancreatitis. On physical examination, she presents with acanthosis nigricans, hirsutism and a skinfold measurement on the thigh of 21mm (RR < 22mm in women). At the time, she had triglycerides (TG) of 1529 mg/dL (RR < 150 mg/dL) and HbA1c of 8.4% (RR < 5.7%), and was positive for PPARG mutation. The patient started fibrate, regular and NPH insulins, metformin and pioglitazone, with good response to clinical treatment during the follow-up. Nowadays, she maintains use of oral antidiabetics, lowering TG down to 217 mg/dL and HbA1c to 6.3%. She has a recent liver ultrasound with mild steatosis - US fat fraction of 11% (RR mild 5-15%), and elastography with METAVIR F0 - 4.8 kPa (RR < 5 kPa) IQR 7.9%. Case 2. A 41-year-old female patient, mother of the index patient, has a previous history of gestational diabetes that progressed to DM with multiple complications, associated with hypertriglyceridemia and metabolic dysfunction-associated fatty liver disease (MAFLD). At the first consultation, the patient presented a TG value of 396 mg/dL and HbA1c of 10.8%, already in use of multiple-dose insulin therapy at 1.2 units/kg/day. During investigation, the patient was also confirmed to have a mutation in the PPARG. Pioglitazone was introduced and insulin adjustment was made, but the patient continued to have difficult glycemic control until the present date. Her most recent liver ultrasound reveals mild steatosis - US fat fraction of 11.5%, and elastography with METAVIR F0 - 4.0 kPa. Case 3. A 14-year-old male, brother of the index patient, was recently brought to our specialized care as an asymptomatic case without comorbidities. He presents no changes on physical examination, a HbA1c of 5.6%, but already with hypertriglyceridemia (TG 310 mg/dL). Conclusion: The clinical features of FPLD3 may exhibit significant diversity, even among individuals sharing identical mutation. However, most cases converge in the severity of metabolic impairments, although experiencing a milder reduction in adipose tissue compared to FPLD2. Mild steatosis at US-derived fat fraction in cases 1 and 2 support less severe changes in fat distribution in FPLD3, leading to suspicion about the influence of the PPARG mutation on insulin sensitivity and metabolic changes.
Presentation: 6/3/2024