Turning back the metabolic disturbances - results of treating two brothers with Berardinelli Seip syndrome with leptin analogue for five months

Lycka Auste Pundziute; Ulrika Harenstam

doi:10.1530/endoabs.110.P453

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Endocrine Abstracts (2025) 110 P453 | DOI: 10.1530/endoabs.110.P453

ECEESPE2025 Poster Presentations Diabetes and Insulin (143 abstracts)

Turning back the metabolic disturbances - results of treating two brothers with Berardinelli Seip syndrome with leptin analogue for five months

Auste Pundziute Lyckå ¹ , 2 & Ulrika Härenstam ¹

Author affiliations

¹Sahlgrenska University Hospital, Queen Silvia Childrens Hospital, Department of Pediatrics, Gothenburg, Sweden; ²Sahlgrenska Academy, University of Gothenburg, Institution for Clinical Sciences, Department of Pediatrics, Gothenburg, Sweden

JOINT3556

Background: Berardinelli-Seip syndrome is a rare autosomal recessive disease, causing generalized lipodystrophy. Affected individuals cannot store fat subcutaneously and thus have very low leptin level and are always hungry. Accumulation of visceral fat in the liver, spleen and skeletal muscles causes insulin resistance and leads to the development of metabolic syndrome and type 2 diabetes. Fat accumulation in the liver may cause liver fibrosis and failure. The metabolic disturbances are difficult to treat without addressing leptin deficiency. Treatment with leptin analogue was previously not used for children in Sweden.

Aim: To present five months treatment results with leptin analogue in two brothers with severe phenotype of generalized lipodystrophy.

Materials: Patients were followed at the Queen Silvia Children’s Hospital since diagnosis. Data on disease history, growth and laboratory values were collected from the hospital records. Informed consent was obtained from the parents.

Results: Both patients have type 2 lipodystrophy caused by BSCL-2 mutation, causing complete absence of the subcutaneous fat. Treatment with leptin analogue was started in July 2024, at the age of 9 yrs and 7 yrs. At the start of the treatment both patients had severe insulin resistance with acanthosis nigricans and have developed type 2 diabetes, treated with maximal doses of metformin and SGLT2 inhibitor, as well as lipid lowering drugs and angiotensin receptor inhibitors for microalbuminuria. Fat accumulation caused severe liver enlargement and fibrosis, meeting criteria of clinical liver cirrhosis. The older brother had developed hypertriglyceridemia and myocardial hypertrophy and was treated with combination of lipid lowering and cardioprotective drugs. Both patients had their tonsils and adenoids removed due to obstructive sleep apnea.

Table 1: .
	Patient 9 yrs old					Patient 7 yrs old
	Max	Baseline	1 mon	3 mon	5 mon	Max	Baseline	1 mon	3 mon	5 mon
Weight (kg)		61	59, 4	57	54		56, 2	54, 1	52, 5	51, 7
BMI		23, 6	22, 8	21, 6	20, 6		23, 6	22, 4	21, 5	21, 2
Waist (cm)		94	91	90	86		90	83, 5	86, 5	80, 5
HbA1c mmol/mol (%)	76 (9, 1)	48 (6, 5)	41 (5, 9)	38 (5, 7)	35 (5, 4)	61 (7, 7)	41 (5, 9)	38 (5, 7)	33 (5, 2)	29 (4, 8)
Fasting insulin (ref 2, 7-17 mIE/l)	130	83	17	6, 2	7, 4	160	66	12	4, 4	8
Triglycerides (ref 0, 5-2, 2 mol/l)	19	3, 5	1, 3	0, 69	0, 85	3, 4	1, 5	0, 75	0. 52	0, 72

Conclusion: Treatment with leptin analogue was safe and effective in reducing the accumulation of visceral fat and reversing the metabolic abnormalities in children with type 2 generalized lipodystrophy.