Metabolic correction induced by leptin replacement treatment in young children with Berardinelli-Seip congenital lipoatrophy.

Abstract

OBJECTIVE:

Berardinelli-Seip syndrome is a rare congenital lipoatrophy with a severe prognosis and no efficient therapy. Children present with low leptin levels and severe metabolic complications (insulin resistance, elevated triglyceride levels, and hepatic steatosis). The objective of this study was to test safety and efficacy of recombinant-methionyl-human leptin replacement in children with Berardinelli-Seip syndrome before development of severe metabolic disease

METHODS:

As part of an open trial, recombinant-methionyl-human leptin was given daily for 4 months to children who did not have diabetes and had Berardinelli-Seip congenital lipoatrophy and metabolic complications at a dosage that was meant to achieve physiologic levels. Six boys and 1 girl (age: 2.4-13.6 years), with a mean fasting insulin level of >15 mIU/L and hypertriglyceridemia, were included.

RESULTS:

At the end of the recombinant-methionyl-human leptin treatment, a 63% reduction of fasting triglycerides level was achieved. A simultaneous 30% increase in insulin sensitivity was seen, and liver volume was reduced by 20.3%. More remarkable, values of insulin sensitivity and triglyceride level were in the reference range in 4 patients.

CONCLUSIONS:

Leptin replacement is able to reverse metabolic complications in the majority of children with Berardinelli-Seip congenital lipoatrophy and with insulin resistance or dyslipidemia before the development of overt diabetes.

• Authors: Jacques Beltrand, Marta Beregszaszi, Didier Chevenne, Guy Sebag, Marc De Kerdanet, Frédéric Huet, Michel Polak, Nadia Tubiana-Rufi, Didier Lacombe, Alex M De Paoli, Claire Levy-Marchal
• Journal: Pediatrics (Pediatrics) Vol. 120 Issue 2 Pg. e291-6 (Aug 2007) ISSN: 1098-4275 [Electronic] United States
• PMID: 17671040 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Leptin

Topics

• Adolescent
• Child
• Child, Preschool
• Female
• Humans
• Leptin (deficiency, metabolism, therapeutic use)
• Lipodystrophy, Congenital Generalized (blood, drug therapy, metabolism)
• Male
• Prospective Studies