Published online August 1, 2007
PEDIATRICS Vol. 120 No. 2 August 2007, pp. e291-e296 (doi:10.1542/10.1542/peds.2006-3165)

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ARTICLE

Metabolic Correction Induced by Leptin Replacement Treatment in Young Children With Berardinelli-Seip Congenital Lipoatrophy

Jacques Beltrand, MD^a, Marta Beregszaszi, MD^a,b, Didier Chevenne, MD^c, Guy Sebag, MD, PhD^d, Marc De Kerdanet, MD^e, Frédéric Huet, MD^f, Michel Polak, MD, PhD^g, Nadia Tubiana-Rufi, MD^h, Didier Lacombe, MD, PhDⁱ, Alex M. De Paoli, MD^j and Claire Levy-Marchal, MD^a

^a Université Paris 7, INSERM U690, Paris, France
^b Clinical Investigation Center
^c Departments of Biochemistry
^d Pediatric Radiology
^h Pediatric Endocrinology and Diabetology, Robert Debré Hospital, Paris, France
^e Pediatric Endocrinology and Diabetology Unit, South Hospital, Rennes, France
^f Department of Pediatrics, Children Hospital, Dijon, France
^g Department of Pediatric Endocrinology, Necker-Enfants Malades Hospital, INSERM EMI363, Paris, France
ⁱ Department of Medical Genetics, Pellegrin Children's Hospital, Bordeaux, France
^j Amgen, Inc, Thousand Oaks, California

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.

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Key Words: leptin • Berardinelli-Seip syndrome • congenital lipoatrophy

Abbreviations: BSCL—Berardinelli-Seip congenital lipoatrophy • r-metHuLeptin—recombinant-methionyl-human leptin • FFA—free fatty acids • QUICKI—quantitative insulin sensitivity check index • ALAT—alanine transaminase • ASAT—aspartate transaminase

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Accepted Jan 26, 2007.

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