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.

Longitudinal evaluation and risk factors of lipodystrophy and associated metabolic changes in HIV-infected children.

OBJECTIVE: To assess the rate of progression of lipodystrophy and the associated metabolic disturbances over a 2-year period in children and to assess risk factors associated with lipodystrophy and metabolic disturbances. DESIGN: Multicenter 2-year prospective study with a standardized evaluation. METHODS: One hundred thirty children (median age = 10 years, 64 boys and 66 girls) receiving antiretroviral therapy were recruited in 3 pediatric clinics. Lipodystrophy was defined based on 4 skinfold thickness measurements. Fasting lipids and glucose profile were measured in all children. RESULTS: The proportion of children presenting with lipodystrophy was 24.6%. Nineteen percent of children had high-density lipoprotein values less than 1 mmol/L. Twenty-two percent and 15% of children had values greater than 2 standard deviations for age and gender for cholesterol and triglycerides, respectively. A total of 13.2% showed insulin resistance. A total of 42.7% showed at least 1 of these biologic disturbances. Prospective follow-up showed no progression at all over 2 years, except for a doubling of the number of children with insulin resistance. In multivariate analyses, ethnicity, previous severe clinical condition, duration of HIV infection, and nucleoside reverse transcriptase inhibitor treatment were significantly associated with lipodystrophy. Tanner stage V of puberty, severe clinical symptoms and protease inhibitor treatment were independently associated with the risk of metabolic disturbances. CONCLUSIONS: Puberty seems to be the time when HIV-infected children taking potent antiretroviral therapy are more likely to develop lipodystrophy and metabolic complications, especially in children with a severe underlying HIV infection. Once developed, lipodystrophy and metabolic changes seem to be extremely stable with time.