Genetic and non-genetic factors that increase the risk of non-syndromic cleft lip and/or palate development

ObjectivesWe investigated the relationship between non-syndromic cleft lip/palate (NSCLP) and polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and RFC1, as well as the corresponding interactions with environmental factors.Subjects and MethodsOne hundred and forty NSCLP patients and their mothers, as well as 175 control individuals and their mothers, were recruited. Information regarding smoking and alcohol consumption was recorded. Blood samples were obtained in order to measure serum folate and cobalamin, as well as, plasma total homocysteine concentrations and to extract DNA. Polymorphisms in MTHFR(677C>T and 1298A>C), MTR(2756A>G), MTR(66A>G), and RFC1(80A>G) were analyzed by PCR–restriction fragment length polymorphism.ResultsAmong the patients, 59.5% had cleft lip and palate, 22.0% had cleft palate, and 18.5% had cleft lip only. Maternal alcohol consumption and reduced folic acid concentrations in both children and mothers (P < 0.001 and P = 0.003, respectively) were risk factors for NSCLP. Patients and their mothers carrying the MTHFR 667T allele showed lower serum folate than CC (P = 0.011 and P = 0.030, respectively). Mothers who carried the MTHFR 1298C allele exhibited increased risk of having a child with NSCLP, after adjusting for alcohol consumption (OR: 1.75, 95% CI: 1.03–2.99, P = 0.038).ConclusionsReduced folic acid levels, alcohol consumption, and the MTHFR 677T and 1298C alleles may have contributed to NSCLP development in this sample population from Rio Grande do Norte.

Diagnóstico pré-natal de défice em proteína trifuncional mitocondrial / Prenatal diagnosis of mitochondrial protein trifunctional deficiency

O diagnóstico pré-natal de doenças hereditárias dometabolismo permite aos casais de risco equacionarem assuas opções reprodutivas de modo a só terem descendentesnão afectados. No caso de défice em proteína trifuncionalmitocondrial (MIM #6090015) ou MPT (complexo multienzimáticoessencial à β-oxidação dos ácidos gordos de cadeialonga de C12 a C18) essa situação reveste-se de grandeimportância dada a elevada letalidade associada à patologia.Os autores apresentam um caso clínico de défice em proteínatrifuncional fatal. O diagnóstico pré-natal (DPN) foidisponibilizado em três gestações, sendo os dois primeirospor doseamento enzimático e o último através de estudomolecular(AU)

The prenatal diagnosis of inherited metabolic diseaseoffers, to at-risk couples, the opportunity to plan theirreproductive options in order to have only unaffectedoffspring.In cases of mitochondrial protein trifunctional deficiency(MIM #6090015) or MPT (multienzyme complexinvolved in the β-oxidation of fatty acids with lengths ofC12-C18) this is an important issue because a high rateof mortality is associated with this disorder.The authors report a neonatal fatal case of MPT deficiency.Prenatal diagnosis was offered in the following 3pregnancies: two by a biochemical approach and the lastone by mutational analysis(AU)

Galactosemia: genotipo y fenotipo de siete pacientes / Galactosemia: the genotype and phenotype of seven patients

Introducción. A pesar de los tratamientos precoces basados en la nutrición, muchos pacientes con galactosemia presentan una enfermedad neurodegenerativa que se manifiesta fundamentalmente a través de alteraciones del lenguaje y discinesias. En las imágenes obtenidas mediante la resonancia magnética (RM) cerebral se pueden visualizar dos tipos distintos de alteraciones: una primera, que se manifiesta con hiperseñal difusa y poco intensa de la sustancia blanca de los centros semiovales, y una segunda, con focos de hiperseñal más intensos rodeando las puntas ventriculares de predominio posterior. Pacientes y métodos. Presentamos los datos clínicos y de imagen de siete niños de edades comprendidas entre los 3 y los 12 años con galactosemia clásica. El inicio había ocurrido típicamente durante la lactancia. Dos niños se desarrollaron de forma normal (10 y 12 años), cuatro presentaban un retraso del desarrollo (10, 7, 4 y 3 años) y uno presentaba una parálisis cerebral distónica (kernícterus). Resultados. La RM cerebral reveló la afectación típica de la sustancia blanca en cinco de los niños: uno con alteración difusa y cuatro con ambos tipos de alteraciones. El paciente con kernícterus mostró lesiones en los ganglios basales. Tres pacientes son homocigóticos para la mutación Q188R, y dos son heterocigóticos compuestos. Conclusión. Se ha hallado una correlación positiva entre el retraso en el desarrollo, la afectación de la sustancia blanca y la mutación clásica Q188R (AU)

Introduction. Despite early dietary therapy, many patients with galactosemia show a neurodegenerative disease specially evident in speech impairment and movement disorders. Magnetic resonance imaging of the brain, show cerebral white matter changes with hypomielinization bilateral and symetrical periventricular hypersignal in T2. Patients and methods. We presented clinical and neuroradiological data of seven children (3 to 12 years of age) with classical galactosemia. All had a typical presentation in neonatal period. Two children had normal development (10 and 12 years-old), four presented developmental delay (10, 7, 4 and 3 years-old), and one showed a dystonic cerebral palsy (kernicterus). Results. The brain MRI showed the typical involvement of white matter, in five children, and basal ganglia abnormalities in the kernicterus patient. Three patients are homozygous for Q188R mutation and two are compound heterozygous. Conclusion. We found a positive correlation among developmental delay, white matter involvement and Q188R mutation (AU)

Outbreak of mumps associated with poor vaccine efficacy - Oporto Portugal 1996.

Vaccination against mumps in Portugal began in 1987, with the introduction of the combined measles, mumps, and rubella vaccine (MMR) in the national vaccination programme (Programa Nacional de Vacinacao: PNV) for both sexes at 15 months. In November 1990,