Effect of metreleptin on metabolic changes in patient with congenital generalized lipodystrophy

Marzhan Rakhimzhanova; Assel Issabayeva; Aigerim Umerzakova; Alina Alzhaxina

Background: Congenital generalized lipodystrophy is a rare and serious genetic disorder that has a profound impact on the quality of life of individuals. The worldwide prevalence of disease is estimated at 1 in 12 million people. It causes significant metabolic abnormalities and may reduce the life expectancy of children and young adults due to the late diagnosis and absence of adequate treatment. Below, we report the case of an 8-year-old boy with Berardinelli-Seip syndrome in Kazakhstan and the results of using metreleptin replacement therapy, especially its positive effect on the lipid profile.

Clinical Case: The boy was admitted to the local hospital at 4 months of age with complaints of high growth but not weight gain, excessive appetite and sweating, skin hyperpigmentation, irritability, abdominal distention, absence of total subcutaneous body fat. At 5 months of age the genomic DNA was isolated from his blood, and full-exome sequencing revealed a homozygous mutation c. 823 C>T (p. R 275 *) on the 8 exons of the BSCL 2 gene. The nonsense mutation found confirms Berardinelli-Seip syndrome (OMIM: 269700). Objectively, he mainly had height SDS +2,75, severe features of acanthosis nigricans, a total absence of subcutaneous fat throughout the body, acromegaloid facial features, and hepatosplenonephromegaly. Metreleptin was initiated in November 2021 as a pathogenetic therapy due to leptin deficiency. Dosage: 0.06 mg/kg/day-1.8 mg subcutaneously.

Table 1. Laboratory test results
	19.10.2016	21.12.2017	08.11.2018	09.02.2021	09.11.2021	19.11.2021	05.12.2022
Total cholesterol(mmol/l)	2,69	3,02	3,51	4,52	3,95	3,75	3,84
LDL (mmol/l)	1,34	1,57	2,04	1,84	2,26	2,45	2,75
HDL (mmol/l)	0,29	0,43	0,62	0,59	0,69	0,77	1,01
Triglycerides(mmol/l)	5,14	6,01	5,47	9,71	9,86	2,81	1,14
Glucose (mmol/l)	4,88	4,0	5,54	10,26	6,34	3,62	5,11
HbA1c (%)	4,3	5,09	5,0	7,76	5,12	5,03	5,14
Insulin (mcME/ml)	27,65	192,4	71,78	91,16	56,04	13,71	13,62
C-peptide (ng/ml)	5,06	14,63		8,01	6,9	3,12	2,59

Conclusion: Metreleptin is the first drug available for the pathogenetic treatment of leptin deficiencies in generalized lipodystrophy. Follow-up after the initiation of the treatment reveals that metreleptin is more effective than supportive symptomatic treatment at significantly lowering HbA1c, triglyceride, and liver enzyme levels. The rarity of the long-term effect of such a specific treatment is uncertain, the findings in this study illustrate that metreleptin has metabolic and clinical benefits, improves mortality, reduces the risk of developing diabetes mellitus, and cardiovascular risks by reducing triglyceride levels and improving insulin sensitivity.

ESPE Abstracts

P1-62