ESPE Abstracts

Aim: To present some therapeutic difficulties in patients with congenital generalized lipodystrophy (CGL) - a rare autosome recessive disorder characterized by complete absence of adipose tissue. For many years therapy was aimed only at metabolic consequences. In the past few years new pathophysiologic treatment has become available.

Methods and materials: We present four girls – currently 25, 22, 16 and 15 years old, who belong to a small religious minority with high consanguinity risk. All of them share the same mutation of AGPAT2 gene.

Results:

Case 1 A 10-years old girl at presentation with typical phenotype, normal glucose tolerance but severe insulin resistance. Lost for follow up in the next 5 years. At 15 she developed symptomatic diabetes, poorly controlled with multiple drug therapy – metformin 2000mg, basal insulin 0.17U/kg/day, thiazolidinedione 45mg, fibrate 200mg, statin 80mg, ACE inhibitor 10mg, SGLT2 inhibitor 5mg and sulfonyulurea 6mg. The last two medications started after 18 years of age. She had bad adherence to therapy, poor metabolic control and many severe complications – liver steatosis, nephropathy, arterial hypertension, necrotizing pancreatitis and peritonitis, menstrual irregularities.

Case 2 The younger sister of case 1, actively tracked down and hospitalized at age of 13, the same phenotype, no symptoms. She had impaired glucose tolerance and mild hypertriglyceridemia with fewer complications - liver steatosis, severe kyphoscoliosis, secondary amenorrhea. On fewer medications – metformin 3000mg, basal insulin 0.16U/kg/day, thiazolidinedione 45mg and oral contraceptive pill. She had better adherence to therapy and satisfactory HbA1c. Currently both sisters are beyond pediatric care.

Case 3 Presented at the age of 13 years with newly diagnosed diabetes and the most severe phenotype features of all four cases so far. Persistent poor metabolic control with early onset of complications (nephropathy, neuropathy, hepatic steatosis, cardiomyopathy, bone cysts, secondary amenorrhea). On multiple drug therapy – metformin 2550mg, basal bolus insulin 0.88U/kg/day, ACE inhibitor 10mg and Metreleptin 5,8mg. In July 2022 Metreleptin therapy was initiated showing metabolic and clinical improvement.

Case 4 Presented at 15 years of age with diabetes symptoms and already developed several complications (nephropathy, cardiomyopathy, arterial hypertension). On multiple drug therapy – metformin 2000mg, basal bolus insulin 0.7U/kg/day, statin 1mg, ACE inhibitor 5mg. Pending for initiation of metreleptin therapy.

Conclusions: Management of patients with CGL is difficult in terms of development of severe complications very early in the course of the disease and poor adherence to multi drug therapy. With the emerging new therapies there are chances for better disease control.