Metabolic correction induced by leptin replacement treatment in young children with Berardinelli-Seip congenital lipoatrophy.
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.
Beltrand
Jacques
J
Université Paris 7, INSERM U690, Paris, France. jacques.beltrand@rdebre.inserm.fr
Beregszaszi
Marta
M
Chevenne
Didier
D
Sebag
Guy
G
De Kerdanet
Marc
M
Huet
Frédéric
F
Polak
Michel
M
Tubiana-Rufi
Nadia
N
Lacombe
Didier
D
De Paoli
Alex M
AM
Levy-Marchal
Claire
C
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D020738:Leptin / Q000172:deficiency / Q000378:metabolism* / Q000627:therapeutic use*; D052497:Lipodystrophy, Congenital Generalized / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D011446:Prospective Studies
D020738:Leptin