Two Japanese infants with congenital generalized lipodystrophy due to BSCL2 mutations.
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.


CONCLUSIONS
Japanese CGL patients with BSCL2 mutations presented with severe insulin resistance, even during infancy, prior to the development of diabetes mellitus.
Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
Atsushi
A
Nishiyama
Mariko
M
Yagi
Hiroyuki
H
Awano
Yo
Y
Okizuka
Taro
T
Maeda
Shinsaku
S
Yoshida
Yasuhiro
Y
Takeshima
Masafumi
M
Matsuo
D002869:Chromosome Aberrations; D018389:Codon, Nonsense / Q000235:genetics*; D003241:Consanguinity; D004252:DNA Mutational Analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics*; D005808:Genes, Recessive / Q000235:genetics; D005951:Glucose Tolerance Test; D006529:Hepatomegaly / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007333:Insulin Resistance / Q000235:genetics*; D007564:Japan; D052497:Lipodystrophy, Congenital Generalized / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed; D014280:Triglycerides / Q000097:blood
C432679:BSCL2 protein, human; D018389:Codon, Nonsense; D044388:GTP-Binding Protein gamma Subunits; D014280:Triglycerides