RESUMO
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.
Assuntos
Códon sem Sentido/genética , Subunidades gama da Proteína de Ligação ao GTP/genética , Resistência à Insulina/genética , Lipodistrofia Generalizada Congênita/genética , Mutação de Sentido Incorreto/genética , Aberrações Cromossômicas , Consanguinidade , Análise Mutacional de DNA , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Feminino , Seguimentos , Genes Recessivos/genética , Teste de Tolerância a Glucose , Hepatomegalia/diagnóstico , Hepatomegalia/genética , Humanos , Lactente , Recém-Nascido , Japão , Lipodistrofia Generalizada Congênita/sangue , Lipodistrofia Generalizada Congênita/diagnóstico , Masculino , Reação em Cadeia da Polimerase , Tomografia Computadorizada por Raios X , Triglicerídeos/sangueRESUMO
We report and discuss a case of Kimura's disease with an unusual eosinophilic epithelioid granulomatous reaction. A 3-year-old Japanese boy with eosinophilia and a high concentration of IgE developed lymphadenopathy and multiple cervical masses. A lymph node biopsy demonstrated the infiltration of eosinophils in the stroma, which is consistent with the findings of Kimura's disease. Interestingly, a number of apoptotic eosinophils was detected in the infiltrating eosinophils. Multiple epithelioid granulomas with central eosinophilic abscesses and necrosis were also observed. Macrophages and giant cells had phagocytosed the apoptotic eosinophils at the edge of the granulomas. In situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay showed that the TUNEL-positive eosinophils were both in the macrophages and in the central eosinophilic abscesses of the granulomas. These findings suggest that the eosinophils had undergone an accelerated apoptosis in this case of Kimura's disease, and that the epithelioid granulomas were produced by phagocytosis of the apoptotic eosinophils by macrophages.
