Two Japanese infants with congenital generalized lipodystrophy due to BSCL2 mutations

Authors: Nishiyama, Atsushi¹; Yagi, Mariko; Awano, Hiroyuki¹; Okizuka, Yo¹; Maeda, Taro²; Yoshida, Shinsaku³; Takeshima, Yasuhiro¹; Matsuo, Masafumi¹

Source: Pediatrics International, Volume 51, Number 6, December 2009 , pp. 775-779(5)

Publisher: Wiley-Blackwell

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Abstract:

Background:

Congenital generalized lipodystrophy (CGL), Berardinelli-Seip syndrome, is a rare autosomal recessive disorder characterized by the generalized absence of adipose tissue at birth, severe insulin resistance early in life, hypertriglyceridemia, hepatomegaly, and the development of diabetes mellitus during puberty. Recently, two genes, BSCL2 and AGPAT2, were identified as causative genes for CGL. It has been reported that patients with BSCL mutations present with more severe clinical findings than those with AGPAT2 mutations. However, the clinical course of CGL caused by BSCL2 mutations in infancy has not been fully elucidated. Methods:

Two Japanese infantile patients with CGL from independent families were examined and underwent an oral glucose tolerance test. Insulin resistance and insulin secretion were estimated using the homeostasis model assessment for insulin resistance and the insulinogenic index, respectively. Sequence analysis of the entire coding region of BSCL2 and AGPAT2 was performed. Results:

Both CGL patients presented with normal glycemic profiles after oral glucose tolerance tests; however, the values from the homeostasis model assessment of insulin resistance were elevated and well above the cut-off point for diagnosis of infant insulin resistance in both patients. One patient possessed a known homozygous nonsense mutation in exon 8 (c.823C>T) of BSCL2; the other had a novel homozygous missense mutation in exon 5 (c.560A>G) of BSCL2. Conclusion:

Japanese CGL patients with BSCL2 mutations presented with severe insulin resistance, even during infancy, prior to the development of diabetes mellitus.

Keywords: Berardinelli-Seip syndrome; BSCL2; congenital generalized lipodystrophy; insulin resistance

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1442-200X.2009.02863.x

Affiliations: 1: Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, 2: Department of Pediatrics, Public Shiso General Hospital and 3: Department of Pediatrics, Toyooka Hospital, Hyogo, Japan

Publication date: 2009-12-01

Two Japanese infants with congenital generalized lipodystrophy due to BSCL2 mutations

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