RESUMEN
AIMS: Abnormalities in the imprinted locus on chromosome 6q24 are the most common causes of transient neonatal diabetes mellitus (6q24-related transient neonatal diabetes). 6q24-Related transient neonatal diabetes is characterized by the patient being small-for-gestational age, diabetes mellitus at birth, spontaneous remission within the first few months and frequent recurrence of diabetes after childhood. However, it is not clear whether individuals with 6q24 abnormalities invariably develop transient neonatal diabetes. This study explored the possibility that 6q24 abnormalities might cause early-onset, non-autoimmune diabetes without transient neonatal diabetes. METHODS: The 6q24 imprinted locus was screened for abnormalities in 113 Japanese patients with early-onset, non-obese, non-autoimmune diabetes mellitus who tested negative for mutations in the common maturation-onset diabetes of the young (MODY) genes and without a history of transient neonatal diabetes. Positive patients were further analysed by combined loss of heterozygosity / comparative genomic hybridization analysis and by microsatellite analysis. Detailed clinical data were collected through the medical records of the treating hospitals. RESULTS: Three patients with paternal uniparental isodisomy of chromosome 6q24 were identified. None presented with hyperglycaemia in the neonatal period. Characteristically, these patients were born small-for-gestational age, representing 27.2% of the 11 patients whose birth weight standard deviation score (SDS) for gestational age was below -2.0. CONCLUSIONS: Abnormalities in the imprinted locus on chromosome 6q24 do not necessarily cause transient neonatal diabetes. Non-penetrant 6q24-related diabetes could be an underestimated cause of early-onset, non-autoimmune diabetes in patients who are not obese and born small-for-gestational age.
Asunto(s)
Enfermedades Autoinmunes/etiología , Trastornos de los Cromosomas/fisiopatología , Cromosomas Humanos Par 6 , Diabetes Mellitus/etiología , Adolescente , Adulto , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/genética , Índice de Masa Corporal , Niño , Trastornos de los Cromosomas/diagnóstico , Trastornos de los Cromosomas/genética , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/genética , Diabetes Mellitus Tipo 2/diagnóstico , Diagnóstico Diferencial , Salud de la Familia , Femenino , Sitios Genéticos , Pruebas Genéticas , Humanos , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Japón , Masculino , Adulto JovenRESUMEN
AIMS: To investigate the molecular and clinical characteristics of the largest series of Japanese patients with glucokinase maturity-onset diabetes of the young (GCK-MODY), and to find any features specific to Asian people. METHODS: We enrolled 78 Japanese patients with GCK-MODY from 41 families (55 probands diagnosed at the age of 0-14 years and their 23 adult family members). Mutations were identified by direct sequencing or multiplex ligation-dependent probe amplification of all exons of the GCK gene. Detailed clinical and laboratory data were collected on the probands using questionnaires, which were sent to the treating physicians.ãData on current clinical status and HbA1c levels were also collected from adult patients. RESULTS: A total of 35 different mutations were identified, of which seven were novel. Fasting blood glucose and HbA1c levels of the probands were ≤9.3 mmol/l and ≤56 mmol/mol (7.3%), respectively, and there was considerable variation in their BMI percentiles (0.4-96.2). In total, 25% of the probands had elevated homeostatic assessment of insulin resistance values, and 58.3% of these had evidence of concomitant Type 2 diabetes in their family. The HbA1c levels for adults were slightly higher, up to 61 mmol/mol (7.8%). The incidence of microvascular complications was low. Out of these 78 people with GCK-MODY and 40 additional family members with hyperglycaemia whose genetic status was unknown, only one had diabetic nephropathy. CONCLUSIONS: The molecular and clinical features of GCK-MODY in Japanese people are similar to those of other ethnic populations; however, making a diagnosis of GCK-MODY was more challenging in patients with signs of insulin resistance.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Angiopatías Diabéticas/epidemiología , Salud de la Familia , Glucoquinasa/genética , Resistencia a la Insulina , Mutación , Enfermedades Vasculares Periféricas/complicaciones , Adulto , Anciano , Sustitución de Aminoácidos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Angiopatías Diabéticas/prevención & control , Femenino , Eliminación de Gen , Estudios de Asociación Genética , Glucoquinasa/metabolismo , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico , Incidencia , Japón/epidemiología , Masculino , Microvasos/efectos de los fármacos , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/epidemiología , Enfermedades Vasculares Periféricas/prevención & control , Polimorfismo de Nucleótido SimpleRESUMEN
We report two cases of sepsis and meningoencephalitis with listeriosis. They died in despite of administering sensitive antibiotics. A 2 day old girl was admitted to our hospital because of fever and cyanosis. Listeria monocytogenes type 4b was cultured from blood, CSF, throat, urine, ear. She was treated with twice exchange transfusion and sensitive antibiotics (ABPC, TOB), but died from DIC. A 48 year old man suddenly experienced an unconscious condition. A CSF culture grew L. monocytogenes type 1/2a. He was treated with sensitive antibiotics (ABPC, CEZ etc), but went bad conditions. Listeria infection of this cases developed as unfortunate infection.