[Preventive program of birth defects: incidence of anencephaly in Maracaibo, Venezuela. 1993-1996 period]. / Programa preventivo de defectos del nacimiento: incidencia de anencefalia en Maracaibo, Venezuela. Período 1993-96.

Incidence of anencephaly in the State of Zulia, and specifically in the Eastern Coast of Lake Maracaibo, an oil exploitation area, has been declared high since the beginning of the 80's, coincident with the generalized use of ultrasound as a diagnostic tool for fetal evaluation. Through the Birth Defects Preventive Program, established at the Hospital Chiquinquirá in Maracaibo, we have developed a fourfold strategy for the study of birth defects: i) analysis of more than 32,332 ultrasound evaluations within the Ultrasound Service, between 1993 and 1996, ii) a case-control malformation registry beginning in 1995, iii) a study of malformed stillbirths at the Pathology Service, observed after 4232 deliveries within this hospital, and iv) a registry of over 638 mothers with high risk pregnancy for fetal defects detected at the prenatal clinic and carried out at the Perinatal Medical Genetics Service. As a reference population we study 345 medical histories obtained from the Medical Genetics and Prenatal Diagnostic Service at Hospital Coromoto, and oil companies related medical facility. This approach has led us to conclude that the incidence of anencephaly in the State of Zulia is 0.75/1000, significantly similar to that expected for most populations.

Plasma excitatory amino acids in autism.

Plasma amino acid levels were measured by high pressure liquid chromatography (HPLC) in fourteen autistic children, all below 10 years of age. Mean glutamic and aspartic acid valued were elevated (169 +/- 142 uM and 22.1 +/- 13 uM respectively) together with taurine (90.1 +/- 78.7 uM) (p > 0.1). All affected children had low levels of glutamine (241 +/- 166 uM; p < 0.01) and asparagine (22.9 +/- 12.9 uM; p < 0.01) as compared to normal values (585 +/- 25 and 59.2 +/- 4.2 uM respectively); eleven children had increased aspartic acid and eight children had high levels of glutamate; seven of these children had a concomitant increment of taurine. The increment of the three above mentioned compounds was observed at the same time only in five children. These findings demonstrate that abnormal plasmatic levels of neurotransmitter amino acids may be found in some autistic children. Increased glutamatemia may be dietary in origin or may arise endogenously for several reasons, among others, metabolic derrangements in glutamate metabolism perhaps involving vitamin B6, defects or blockage of the glutamate receptor at the neuronal compartment, or alterations in the function of the neurotransmitters transporters. Increments of taurine, an inhibitor, is likely compensatory and calcium dependent.

[Epidemiology of congenital malformations in Bolivar City, Venezuela. Analysis of the consanguinity factor]. / Epidemiología de las malformaciones congénitas en Ciudad Bolívar, Venezuela. Análisis del factor consanguinidad.

The proportion of consanguineous matings and average inbreeding coefficients were established and compared in a sample of families with incidence of malformed newborns or stillborns as well as in paired normal controls. All children were born at the Ruiz y Páez Hospital in Ciudad Bolívar between april 1978 and june 1990. The samples included 2406 normal newborns (No), 2403 malformed newborns (Ma) and 50 malformed stillborns. The second sample was subdivided into 1934 with a single malformation (Mo), 315 with polimalformations (Po), 77 cases with Down syndrome (Do) and 77 with malformations of the central nervous system (SNC). Statistically significant differences were found in the frequency of consanguineous matings for the Ma, Po and Do groups when compared to the No group. A higher proportion of first cousins matings among parents of the Po and Do groups was found at F = 1/16, F = 1/64 and 1/32, in that order. A statistically significant absence of type I first cousins matings and a non significant predominance of type II first cousins matings were found, which might be pointing out to particular ways of mating behavior in this population, related to socio-cultural custom. Average F values for the No group were found to be similar to others reported for Venezuelan and Latin-American populations. Studies like this, help in providing basic parameters for the venezuelan population genetics.

Síndrome de Down: herencia, selección prenatal y aborto espontáneo / Down's syndrome: heredity, prenatal selection and spontaneous abortion

La frecuencia de los matrimonios consanguíneos y los coeficientes de consanguinidad, se investigaron en progenitores y probados en trescientos catorce genealogías de familias con síndromes de Down. La frecuencia de uniones consanguíneas y/o isonímicas, fue del 8% entre los progenitores de los niños con síndrome de Down, y del 4,8% entre los abuelos maternos de los mismos. Ambas cifras son significativamente diferentes del porcentaje esperado de uniones consanguíneas en esta población (2%). El coeficiente de consanguinidad (F), para todos los propósitos (17,5 x 10~4) y el de las madres menores de ®35, > años (12,64 x 10~4), resultó significativamente mayor que el F promedio de esta población (8 x 10~4). El F promedio de las madres de edad igual o mayor de 35 * > 35 > años y el de los esposos de las madres sin distingo de edades, no estaba aumentado. Las madres de niños con síndrome de Down, presentaron también un número significativamente mayor de pérdidas reproductivas. Además, el origen geográfico de las familias con síndrome de Down, tiende a ser preferencial. Estos hallazgos favorecen la hipótesis, de que la disyunción cromosómica y la selección prenatal de productos con aneuploidias cromosómicas, está genéticamente controlada por genes autosómicas

Programa diagnóstico de enfermedades metabólicas / Diagnostic programs of metabolic diseases

Se presentan y discuten los métodos, resultados y causas de error de los últimos 3 años de estudio de el programa diagnóstico para enfermedades metabólicas, el cual se lleva en la Unidad de Genética y el Departamento de Pediatría del Hospital Universitario de Maracaibo, desde mediados de 1974. Con el fin de señalar entre las posibles causas de error diagnóstico, las inherentes a la habilidad en la interpretación de las pruebas, las cuales se describen en el texto, se comparan los resultados interpretados por dos diferentes investigadores en dos distintos períodos de estudio. Se señala la importancia de la intervención del pediatra genetista bioquímico en el cuidado del paciente metabólico y se resume la patología encontrada. Muchos de estos casos son primeras descripciones en la literatura médica zuliana y quizá venezolana: por ejemplo, tirosinemia hereditária, gangliosidosis generalizada, galactosemia, enfermedad de Krabbe y otras

The spectrum of frontonasal dysplasia in an inbred pedigree.

An inbred pedigree is described in which three members were affected with FND (Frontonasal Dysplasia). Two of these individuals were products of a consanguineous mating with an inbreeding coefficient of F = 0.0391. The third affected individual (propositus), was born to a marriage in which the coefficient of inbreeding was 0.0742. The mother of the propositus, whose inbreeding coefficient was 0.0625, had borderline hypertelorism and a broad nose. Several other members of the pedigree who had hypertelorism were products of consanguineous matings. The presence of consanguinity in all individuals affected with a variety of manifestations of FND suggests a genetic mechanism for this malformation.

Duplication 8p syndrome: studies in a family with a reciprocal translocation between chromosomes 8 and 12.

We report a family in which six individuals were carriers of a translocation between chromosomes 8 and 12. The balanced carriers had a chromosomes constitution: 46,XX or 46,XY,t(8;12)(021;p13). Six individuals in five generations were mentally retarded. Three of them were examined; their chromosome constitution was 46,XX or 46,XYder(12),t(8;12)(p21;p13); thus they had a duplication of 8pter leads to 8p21 and possible deficiency of 12pter leads to 12p13. The activities of the enzymes that are coded by genes on 8p (glutathione reductase, GSR, E.C. 1.6.4.2.) and 12p (triosephosphate isomerase, TPI, E.C. 5.3.1.1.; lactate dehydrogenase-B, LDH-B, E.C. 1.1.1.27.; and glyceraldehyde-3-phosphate dehydrogenase, G3PD, E.C. 1.2.1.12.) were normal in these individuals. These findings helped in interpreting the position of the break points in the respective chromosomes. The phenotypic findings in our patients are discussed. Segregation analysis indicates no significant variation from a 25% recurrence risk for each of the possible genotypes in the offspring of balanced carriers.

Familial partial trisomy of the long arm of chromosome 10 (q24-26).

Two fourth cousins with a strikingly similar pattern of malformation and who have an unbalanced translocation (46, XY, -17, +t (17p; 10q) are described. From an analysis of the phenotypes of these patients and others reported with 10q trisomy, we propose that the trisomy 10q 24-26 syndrome includes: growth and mental retardation, a characteristic facies (microcephaly, flat face with spacious forehead, small nose, depressed nasal bridge, arched wide-spaced eyebrows, blepharophimosis, microphthalmia, low-set ears, bow-shaped mouth with prominent upper lip, micrognathia), palate anomalies (high-arched cleft or agenesis), congenital heart disease, and anomalies of the hands and feet. Anomalies common to the cousins, but not described in other patients with trisomy 10q, are believed to be expressions of a partial monosomy of 17p.