RESUMEN
We report on a female infant presenting with psychomotor retardation and facial dysmorphism. Cytogenetic studies showed an abnormal chromosome 14 with ectopic NOR sequences at the extremity of the long arm with a terminal 14q32.33 deletion. Review of the eight cases with pure terminal 14q32.3 deletions described to date documented that our observation is the smallest terminal 14q deletion ever reported. Thus, genotype-phenotype correlation allows us to delimit the critical region for mental retardation, hypotonia, epi-telecanthus, short bulbous nose, long philtrum, thin upper lip, and small mouth observed in 14 qter deletions to the subtelomeric 1.6 Mb of chromosome 14.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 14/genética , Encéfalo/anomalías , Preescolar , Anomalías Craneofaciales/genética , Citogenética , Femenino , Genotipo , Humanos , Hibridación Fluorescente in Situ , Lactante , Discapacidad Intelectual/genética , Hipotonía Muscular/genética , Miopía/genética , FenotipoRESUMEN
AIM: To identify predictive factors of the presence of a serious bacterial infection (SBI) in febrile infants less than three months old. METHODS: Retrospective analysis of the medical files of 315 consecutive consultations of febrile infants less than three months old in the pediatric emergency department of a French hospital, with logistic regression multivariate analysis of the different criteria routinely considered and C-reactive protein (CRP). RESULTS: SBI were diagnosed in 79 (25.1%) infants, primarily urinary tract infections (71; 22.5%). One of these 79 children had pneumococcal meningitis but met the classical criteria for low risk of SBI: he died because antibiotics were not prescribed sufficiently early. Factors significantly associated with SBI were: male sex; temperature >38.5 degrees C and lasting >24 hours; poor general condition; absence of ear, nose and throat symptoms; high white blood cell count with >50% neutrophils; and serum CRP concentration >20 mg/l. Multivariate analysis entering all these items retained only the latter two (respectively, OR: 13.5, 95% CI: [6.5-28.2] and OR: 2.9; 95% CI: [1.3-6.3]). CRP <20 mg/l and <50% neutrophils had a negative-predictive value of 93.1% for the absence of SBI. CONCLUSIONS: At present, no factor(s) is(are) able to predict with 100% accuracy the absence of SBI in febrile infants less than three months old. The risk of severe sequelae or death caused by untreated SBI would seem to justify the prescription of antibiotics until microbacterial culture results become available.
Asunto(s)
Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/complicaciones , Femenino , Fiebre/etiología , Humanos , Lactante , Recién Nacido , Masculino , Análisis Multivariante , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Rotavirus nosocomial infection (RNI) is frequent in pediatric units. This study was designed to determine the incidence and the main risk factors of RNI in children aged 3 months-3 years and admitted for at least 48 hours days during the epidemic period. PATIENTS AND METHODS: A stool sample was obtained within the 24 hours of admission. An additional sample was collected from rotavirus-negative children either the day of discharge, or when they developed abnormal clinical signs. Parents were contacted by phone after discharge. Children initially rotavirus-negative and positive 2 days or more after admission were considered as certain nosocomial cases. In the absence of the second sample, possible nosocomial cases were considered if new symptoms (i.e.; fever and or digestive symptoms) occurred 2 days or more after the first negative sample. RESULTS: One hundred and seventeen children were included. The incidence was 11.1% for certain NRI, 16.8% for possible hospital-acquired cases and 19.4% for the whole cases. Possible risk factors were the low number of nurses during the weekend, the great number of medicine students in the unit, and no use of individual material. CONCLUSION: NRI have a high incidence, whose reality can only be approximated by taking into account the possible NRI occurring at home after hospital-discharge.
Asunto(s)
Infección Hospitalaria/virología , Infecciones por Rotavirus/transmisión , Niño Hospitalizado , Preescolar , Infección Hospitalaria/epidemiología , Heces/virología , Femenino , Francia/epidemiología , Humanos , Incidencia , Lactante , Masculino , Factores de Riesgo , Rotavirus/aislamiento & purificación , Infecciones por Rotavirus/epidemiologíaRESUMEN
Eleven patients with glycogen storage disease type Ib (GSD Ib) were studied. Using a combination of single-strand conformation polymorphism (SSCP) analysis, restriction enzyme digestion and direct sequencing, we were able to identify 21/22 mutant alleles comprising 12 different mutations in the glucose-6-phosphate translocase gene (G6PT). Among these, one is a novel mutation of G6PT: 855T>C (L229P).
Asunto(s)
Alelos , Enfermedad del Almacenamiento de Glucógeno Tipo I/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Fosfotransferasas/genética , Adolescente , Adulto , Antiportadores , Niño , Preescolar , Enzimas de Restricción del ADN/farmacología , Exones , Francia , Variación Genética , Humanos , Intrones , Proteínas de Transporte de Monosacáridos , Mutación , Polimorfismo Conformacional Retorcido-Simple , Análisis de Secuencia de ADNRESUMEN
Hyperuricemia is a well-known consequence of glucose-6-phosphatase (G6Pase) deficiency, the enzymatic abnormality that characterizes glycogen storage disease (GSD) Type Ia. However, acute gout as the presenting manifestation of GSD Type Ia has been reported in only a few patients. We report a new case in a 17-year-old male evaluated for acute gouty tendinitis in the right Achilles tendon. Blood tests showed chronic acidosis with high levels of uric acid, lactic acid, and cholesterol. A liver enzyme study confirmed the diagnosis of GSD Type Ia. A genetic study showed that the index patient and his sister were composite heterozygotes for the known mutation R83C and the previously unreported mutation M5R. Acute gout in an adolescent with liver enlargement and high blood levels of uric acid and cholesterol should suggest GSD. Demonstration by molecular biology techniques of a mutation in both alleles of the G6Pase gene establishes the diagnosis of GSD Type Ia, obviating the need for a liver biopsy.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo I/diagnóstico , Gota/complicaciones , Tendinopatía/etiología , Adolescente , Femenino , Enfermedad del Almacenamiento de Glucógeno Tipo I/complicaciones , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Heterocigoto , Humanos , Masculino , MutaciónAsunto(s)
Estatura/genética , Deleción Cromosómica , Trastornos del Crecimiento/genética , Cromosoma X/ultraestructura , Estatura/efectos de los fármacos , Desarrollo Óseo , Niño , Preescolar , Salud de la Familia , Femenino , Eliminación de Gen , Trastornos del Crecimiento/tratamiento farmacológico , Humanos , Cariotipificación , FenotipoRESUMEN
Forty-eight patients with glycogen storage disease type Ia (GSD Ia) were studied. Using a combination of single-strand conformation polymorphism (SSCP) analysis, restriction enzyme digestion and direct sequencing, we were able to identify 93/96 mutant alleles, comprising 23 different mutations in the glucose-6-phosphatase gene (G6PC). Among these, 7 are novel mutations of G6PC: M5R, T111I, A241T, C270R, F322L, and two deletions, 793delG and 872delC, resulting in the same mutation at the amino acid level, fs300Ter (300X).
Asunto(s)
Heterogeneidad Genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Alelos , Francia/epidemiología , Glucosa-6-Fosfatasa/genética , Glucosa-6-Fosfatasa/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo I/enzimología , Enfermedad del Almacenamiento de Glucógeno Tipo I/epidemiología , Humanos , Hígado/enzimología , Mutación/genética , Prevalencia , Eliminación de Secuencia/genéticaAsunto(s)
Azatioprina/efectos adversos , Ciclosporina/uso terapéutico , Hepatitis Autoinmune/tratamiento farmacológico , Inmunosupresores/efectos adversos , Enfermedades Pulmonares Intersticiales/inducido químicamente , Adolescente , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Femenino , Hepatitis Autoinmune/patología , Humanos , Inmunosupresores/uso terapéutico , Hígado/patología , Prednisona/uso terapéuticoRESUMEN
In patients with glycogen storage disease type Ia (glucose-6-phosphatase deficiency), serum triglyceride concentrations are markedly raised, whereas phospholipids and cholesterol levels are only moderately elevated. In addition, both VLDL and LDL lipoprotein fractions are raised. Despite these abnormalities, endothelial vascular dysfunction and atherosclerosis seem to be rare in such patients. In view of the crucial role of apolipoprotein E (apoE) in lipid metabolism, we studied both apoE polymorphism (40 patients) and serum concentration (20 patients) in patients with glycogen storage disease type Ia. The distribution of each allele at the apoE locus was similar to that reported in the general population, whereas serum apoE concentrations were raised in our patients. Raised apoE levels in the serum could play an important role in counterbalancing the at-risk-for-atherosclerosis lipid profile of patients with glycogen storage disease type Ia. Moreover, E3 and E4 polymorphisms, predominant in our patients, have a high triglyceride binding capacity and are thus able to increase triglyceride clearance. However, the origin of raised concentrations of apoE is not completely clear though, bearing in mind previous reports regarding serum protein concentrations in such patients, increased hepatic synthesis is likely.
Asunto(s)
Apolipoproteínas E/sangre , Apolipoproteínas E/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/sangre , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Polimorfismo Genético/genética , Adolescente , Adulto , Alelos , Niño , Preescolar , Femenino , Genotipo , Humanos , Lípidos/sangre , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: During pregnancy, Apolipoprotein (Apo) E is synthesized in the placenta to facilitate the uptake of maternal lipoproteins. Preeclampsia is associated with an abnormal lipid profile. Apo E levels may affect the production of nitric oxide. We investigated whether Apo E variations could be related to the high lipid levels and nitric oxide secretion in preeclamptic women. METHODS: Blood samples from 15 normotensive women and 12 mild and 23 severe cases of preeclampsia were assayed for standard lipid profile, Apo E, and nitrate. Urine samples were analyzed for nitrate and cyclic GMP. RESULTS: In women with mild preeclampsia, the triglyceride concentration was significantly higher (p < 0.05) than in normotensive women (3.30 +/- 1.38 versus 2.31 +/- 0.92 g/L) and associated with a higher (p < 0.01) triglyceride/Apo E ratio (0.71; range = 0.40-1.70). In women with severe preeclampsia, the triglyceride/Apo E ratio was similar to normotensive women [0.39 (range = 0.18-1.19) versus 0.41 (range = 0.18-0.79)] associated with a normal triglyceride level and a twofold higher serum nitrate level [36 (range = 1-63 mumol/L) versus 14 (range = 1-37 mumol/L)]. CONCLUSION: The triglyceride/Apo E ratio is significantly higher in mild preeclampsia. In the severe form, this ratio is similar to that of normotensive pregnant women, probably due to a better uptake of triglyceride. Moreover, in the severe form, it is associated with a twofold normal serum nitrate level. Thus, Apo E and the nitric oxide status may be implicated in preeclampsia.
Asunto(s)
Apolipoproteínas E/sangre , Nitratos/sangre , Preeclampsia/sangre , Triglicéridos/sangre , Femenino , Humanos , Óxido Nítrico/fisiología , EmbarazoRESUMEN
Three children with Jeune syndrome (asphyxiating thoracic dystrophy) had clinical and laboratory evidence of liver disease. In two patients the disease evolved to biliary cirrhosis, whereas in the third it was recognized when extensive fibrosis was developing. In the three patients, treatment with ursodeoxycholic acid appeared to control the progression of the hepatic dysfunction.
Asunto(s)
Asfixia Neonatal/complicaciones , Hepatopatías/complicaciones , Osteocondrodisplasias/complicaciones , Alanina Transaminasa/sangre , Alanina Transaminasa/efectos de los fármacos , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/efectos de los fármacos , Asfixia Neonatal/tratamiento farmacológico , Asfixia Neonatal/patología , Niño , Preescolar , Colagogos y Coleréticos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Hepatopatías/tratamiento farmacológico , Hepatopatías/patología , Masculino , Osteocondrodisplasias/tratamiento farmacológico , Osteocondrodisplasias/patología , Resultado del Tratamiento , Ácido Ursodesoxicólico/uso terapéutico , gamma-Glutamiltransferasa/sangre , gamma-Glutamiltransferasa/efectos de los fármacosRESUMEN
Jaundice associated with hypertrophic pyloric stenosis was recognised in three patients; previous reports have suggested that this is a possible early manifestation of Gilbert syndrome. Most patients with Gilbert syndrome are homozygous for a (TA)(7)TAA polymorphism in the gene promoter coding for bilirubin glucuronosyltransferase. Two of the reported patients were homozygous for the (TA)(7)TAA polymorphism whereas the third was heterozygous for the same polymorphism. Furthermore, no other factors contributing to jaundice in the three patients were found. These results suggest that jaundice associated with hypertrophic pyloric stenosis is due to molecular defects within the gene promoter.
Asunto(s)
Enfermedad de Gilbert/complicaciones , Ictericia/etiología , Estenosis Pilórica/etiología , Adulto , Femenino , Enfermedad de Gilbert/genética , Glucuronosiltransferasa/genética , Heterocigoto , Homocigoto , Humanos , Lactante , Recién Nacido , Masculino , Polimorfismo Genético , TATA Box/genéticaRESUMEN
An 18-month-old girl presented with macrocytic megaloblastic anaemia followed by haemolytic uraemic syndrome. Metabolic investigations led to the identification of an inborn error of cobalamin metabolism consisting of defective methylcobalamin biosynthesis, probably cobalamin G, since methionine synthase activity was decreased under standard reducing conditions. Despite treatment, pulmonary hypertension progressively developed and responded to oxygen therapy. Renal involvement evolved to terminal failure and haemodialysis, while pulmonary hypertension was controlled by oxygen therapy. Such clinical manifestations have never been reported in association with a defect of methylcobalamin and thus of methionine biosynthesis. A congenital abnormality of cobalamin metabolism was suspected then confirmed in the presence of typical haematological features associated with unusual clinical manifestations such as progressive renal failure and pulmonary hypertension.
Asunto(s)
5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/deficiencia , Síndrome Hemolítico-Urémico/etiología , Hipertensión Pulmonar/etiología , Vitamina B 12/metabolismo , Anemia Megaloblástica/complicaciones , Femenino , Humanos , Lactante , Errores Innatos del Metabolismo/complicaciones , Metionina/metabolismoRESUMEN
Three novel mutations, Q54P, W70X and T1081, were identified in the gene encoding glucose-6-phosphatase in three patients with glycogen storage disease type Ia. Two sibs of Portuguese origin were homozygous for the Q54P mutation whereas the third patient, originating from both France and Lebanon, was a compound heterozygote for the W70X and T108I mutations. Glycogen storage disease type Ia is a heterogeneous autosomal recessive condition.
Asunto(s)
Glucosa-6-Fosfatasa/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Mutación , Enfermedad del Almacenamiento de Glucógeno Tipo I/enzimología , HumanosRESUMEN
Glycogen storage disease type Ia (GSD Ia) is an autosomal recessive condition, caused by a deficiency of hepatic glucose-6-phosphatase (G6Pase) activity. In a consanguineous family originating from northern Africa whose first daughter was affected with GSD Ia, we were able to identify the disease-causing mutation, a cytosine to thymine substitution at nucleotide 326 in exon 2 of the G6Pase gene (R83C). This mutation causes the disappearance of an HgaI site, and is thus easily detectable by restriction enzyme digestion. Both parents were heterozygous for this mutation. During the third pregnancy, fetal genomic DNA was extracted from a chorionic villus biopsy sampled at the 24th week of gestation. Exons 2 of the G6Pase gene were amplified by the polymerase chain reaction followed by HgaI digestion. Fetal DNA analysis indicated that the fetus had received both normal G6Pase alleles. This result was confirmed after birth. DNA analysis is the only reliable method for prenatal diagnosis of GSD Ia.
Asunto(s)
Análisis Mutacional de ADN , Enfermedad del Almacenamiento de Glucógeno Tipo I/diagnóstico , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Diagnóstico Prenatal , Consanguinidad , Desoxirribonucleasas de Localización Especificada Tipo II/metabolismo , Femenino , Glucosa-6-Fosfatasa/genética , Homocigoto , Humanos , Linaje , Reacción en Cadena de la Polimerasa , Polimorfismo Conformacional Retorcido-Simple , EmbarazoRESUMEN
Six fetuses with normal chromosomes were found to have severe craniofacial, limb, and visceral malformations during the second trimester of pregnancy. Two of these fetuses were monozygotic twins while a third one had a healthy dizygotic twin brother. A case with familial recurrence was also observed. Autopsy and skeletal radiographs suggested several diagnoses such as neural tube defect with limb defects or XK aprosencephaly. The development of these severe conditions in monozygotic twins and familial recurrence emphasize the difficulties of genetic counseling in such situations. These cases may suggest autosomal recessive inheritance.
Asunto(s)
Anomalías Teratoides Graves/genética , Genes Recesivos/fisiología , Deformidades Congénitas de las Extremidades/genética , Defectos del Tubo Neural/genética , Anomalías Teratoides Graves/diagnóstico por imagen , Encéfalo/anomalías , Encéfalo/diagnóstico por imagen , Femenino , Humanos , Deformidades Congénitas de las Extremidades/diagnóstico por imagen , Masculino , Defectos del Tubo Neural/diagnóstico por imagen , Embarazo , Radiografía , Síndrome , Gemelos Dicigóticos , Gemelos MonocigóticosRESUMEN
A three-year-old child affected by glycogen storage disease (GSD) type Ia presented with acute hemiplegia secondary to Moyamoya disease. So far, the association of moyamoya with GSD Ia had only been reported twice. The rarity of both conditions makes their association unlikely to be a chance event and an etiological relationship between them must be considered.
Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo I/complicaciones , Enfermedad de Moyamoya/complicaciones , Preescolar , Hemiplejía/etiología , Humanos , Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/etiología , MasculinoRESUMEN
BACKGROUND: Hepatocellular adenomas may develop in patients with glycogen storage disease types I and III, and the malignant degeneration of adenomas in hepatocellular carcinoma has been reported in ten cases. The aim of this work was to study the characteristics of hepatic adenomas in a large series of 43 patients with glycogen storage disease types I and III and to determine the optimal means of follow-up. METHODS: The charts of 43 patients with glycogen storage disease type I and III were studied. In all these patients, abdominal ultrasonography and the determination of serum alpha-fetoprotein had been performed yearly and serum concentrations of several proteins were determined once. RESULTS: 51.8% of patients with type I and 25% of patients with type III glycogen storage disease had hepatic adenomas at the time of the study. The male to female ratio was 2 to 1 in type I, and no female had adenomas in type III. No evidence of malignant transformation was observed during the follow-up period. Serum concentrations of several proteins were significantly higher in patients with hepatic adenomas than in patients without such lesions. CONCLUSIONS: In patients with glycogen storage disease type I and III, the determination of alpha-fetoprotein serum concentration has to be combined with yearly hepatic ultrasound examinations. Other investigations such as CT scan should be considered when the size of any adenoma increases. The malignant transformation of hepatocellular adenoma into hepatocellular carcinoma remains a rare event.