Tyrosinemia type II: Mutation update, 11 novel mutations and description of 5 independent subjects with a novel founder mutation.

BACKGROUND: Tyrosinemia type II, also known as Richner-Hanhart Syndrome, is an extremely rare autosomal recessive disorder, caused by mutations in the gene encoding hepatic cytosolic tyrosine aminotransferase, leading to the accumulation of tyrosine and its metabolites which cause ocular and skin lesions, that may be accompanied by neurological manifestations, mostly intellectual disability. AIMS: To update disease-causing mutations and current clinical knowledge of the disease. MATERIALS AND METHODS: Genetic and clinical information were obtained from a collection of both unreported and previously reported cases. RESULTS: We report 106 families, represented by 143 individuals, carrying a total of 36 genetic variants, 11 of them not previously known to be associated with the disease. Variants include 3 large deletions, 21 non-synonymous and 5 nonsense amino-acid changes, 5 frameshifts and 2 splice variants. We also report 5 patients from Gran Canaria, representing the largest known group of unrelated families sharing the same P406L mutation. CONCLUSIONS: Data analysis did not reveal a genotype-phenotype correlation, but stressed the need of early diagnosis: All patients improved the oculocutaneous lesions after dietary treatment but neurological symptoms prevailed. The discovery of founder mutations in isolated populations, and the benefits of early intervention, should increase diagnostic awareness in newborns.

[Epidemiology of progressive intellectual and neurological deterioration in childhood. A multicentre study in the Community of Valencia]. / Epidemiología del deterioro intelectual y neurológico progresivo en la infancia. Estudio multicéntrico en la Comunidad Valenciana.

BACKGROUND: Progressive intellectual and neurological deterioration (PIND) in childhood has an incidence of 0.5 per thousand live births. Its impact on morbimortality is important. The aim of this work is to study the epidemiology of PIND and the most important causes of this process. METHODS: A retrospective and multicentre study was carried out in different hospitals of the Valencian Community (Spain). CASE DEFINITION: age less than 18 years with a progressive loss of intellectual or development abilities, previously acquired for at least 3 months. RESULTS: Nine hospitals participated in the study and a total of 85 cases were included. The mean age at the onset of symptoms was 1.8 years, and the mean age at diagnosis was 3.6 years. In 68% of cases there was an intellectual or developmental delay before the onset of symptoms. The mortality rate was 16.4%. A diagnosis was achieved in 74% of the cases. The most frequently found cause was Rett syndrome. More than two-thirds (68%) of diagnosed cases were due to a metabolic disease. DISCUSSION: The existence of a previous development delay and the early onset of the PIND can make it difficult to identify. Like the rest of the series, the largest number of diagnosed cases involved a metabolic disease. CONCLUSIONS: PIND has an early onset, and in a large percentage of cases the origin remains unknown and with a high mortality rate.

[Evaluation of carotid intima-media thickness in familial hypercholesterolemia in childhood]. / Evaluación del grosor del complejo íntima-media de la carótida en la hipercolesterolemia familiar durante la infancia.

INTRODUCTION: Familial hypercholesterolemia (FH) is characterized by exposure to severely elevated LDL-cholesterol from birth, which produces lipid deposits, which can be measured by means of intima-media thickness (IMT). SUBJECTS AND METHODS: The IMT and concentrations of cholesterol and its fractions, triglycerides, alipoproteins Apo-A1, Apo-B and endothelial risk factors (homocysteine and high sensitivity protein C ) were determined in 89 patients (44 males) from 2 to 19 years (9.54+/-3.91 years). IMT was measured by ultrasound using a 12MHz linear array transducer in both carotids to 1cm of the bulb. The IMT mean was compared with age, sex and analytical parameters using multiple regression analysis. RESULTS: The mean values were: IMT 0.334+/-0.088mm, total cholesterol 273.62+/-91.93mg/dl, LDL-cholesterol 204.21+/-86.16mg/dl, LDL/HDL 3.83+/-1.45, apoprotein A1 134.61+/-26.49mg/dl, apoprotein B 130.59+/-40.59mg/dl, homocysteine (median) 7.16mmol/dl, Protein C (median) 0.3mg/l. Using multiple regression analysis, only age was associated with IMT (P=0.049), a mean 0.005mm (95% CI: 0.000-0.010) being the annual increase: up to 12 years the increase in IMT was 0.002mm/year on (95% CI: -0.007-0,010) and then from that age it was 0.013mm/year (95% CI: -0.023-0.049). CONCLUSIONS: The measurement of the carotid IMT could become an objective parameter in the evaluation of the FH in childhood. In our study, it is only associated with age, the increase being most marked from 12 years onwards.

[Drinking water in infants]. / Agua de bebida en el lactante.

We review types of public drinking water and bottled water and provide recommendations on the composition of water for infants. Water used with any of the commercial infant formulas in Spain should contain less than 25 mg/l of sodium. Drinking water must be boiled for a maximum of one minute (at sea level) to avoid excessive salt concentration. Bottled water need not be boiled. Fluoride content in drinking water should be less than 0.3 mg/l in first year of life to prevent dental fluorosis. Nitrate content in water should be less than 25 mg/l to prevent methemoglobinemia. Water with a calcium concentration of between 50 and 100 mg/l is a dietary source of calcium since it provides 24-56 % of the required daily intake in infancy.

[Toxic habits in relation to cancer of the larynx]. / Hábitos tóxicos en relación con el cáncer de laringe.

Various modifiable toxic risk factors for cancer of the larynx were evaluated in our geographic area in a retrospective epidemiological study of a sample of 373 patients diagnosed as cancer of the larynx chosen randomly at the La Fe Hospital of Valencia Spain over a 5-year period. A "z" test of the contrast of proportions of the laryngeal cancer series studied and the results of a National Health Survey showed significant differences between the two study populations (p < 0.05). Compared with the National Health Survey, smoking had an odds ratio (OR) of 72.21 (33.10 < OR < 166.31) (p < 0.05, Mantel-Haenszel test). The association between smoking and cancer of the larynx increased with the dose. Alcohol consumption had an OR: 1.52 (1.09 < OR < 2.11) (p < 0.05, Mantel-Haenszel test). Smoking carried a risk of 71.21 and had an etiological fraction of 98.61% (IC 95%: 65.17-100%), thus representing 98.61% of all etiological factors. Control of smoking could have prevented 65.17-100% of cases of cancer of the larynx (243 cases in our series). Alcohol consumption had a risk of 0.52 and etiological fraction of 34.21% (IC 95%: 2.38-100%). Control of alcohol use could have prevented cancer of the larynx in 2.38-100% of cases (9 cases in our series).

[Single or double dose of vaccine needed for the eradication of measles in Spain?]. / Una o dos dosis de vacuna para erradicar el sarampión en España?

A descriptive and retrospective epidemiological study of measles vaccinations was realized. This study involved 112 children hospitalized in Valencia (Spain) for measles during the period from January 1983 to December 1988. We compared children that had received vaccination and those children that had not. Statistically significant differences were observed in regards to the age of the child (p < 0.025) and the year in which the cases were diagnosed (p < 0.05). The evolution of measles in Spain and in the United States shows the need for revaccinations, as well as the need to augment the coverage of vaccinations in order to eradicate this disease.

[Epidemiologic study of 245 cases of children hospitalized with measles]. / Estudio epidemiológico de 245 casos de niños ingresados por sarampión.

OBJECTIVE: The object of the present study is an analysis of the characteristics common to children hospitalised because of measles. DESIGN: A retrospective descriptive study was made of all the children in hospital with measles over a six month period. SITE. The study was carried out in the Hospital Infantil La Fe, in Valencia. PATIENTS OR OTHERS PARTICIPANTS: All of the children taken into hospital between January 1983 and December 1988, with diagnosed measles as a stated factor in their hospitalisation, aged between 4 months and ten years. INTERVENTION: Treatments were extremely varied, depending on the symptoms of the patient. In most cases an antithermic or analgesic was administered (70%). MEASUREMENTS AND MAIN RESULTS: The data was compiled from clinical histories. We note two epidemics, in 1983 and 1987. 58% of the children were less than 3 years old, and the average age observed was 2.73 years (SD = 2.40). The standard rate of body mass, (PE-IMC) in 81% of the cases, averaged -1.129, and the SD was 1.431, significant with respect to the general population (p 0.001). Only 14% of the children had been previously vaccinated. 76% of the children presented complications. CONCLUSIONS: New risk factors were not identified. Most notable was the importance of nutritional state and correct vaccination.

[Nitrates in drinking water in the Valencia community. Indirect risk of methemoglobinemia in infants]. / Nitratos en las aguas de consumo público de la comunidad valenciana. Riesgo indirecto de metahoglobinemia en el lactante.

An analysis is made of the concentration of nitrates in the public drinking water of the Valencia Community (Spain), corresponding to 467 municipalities and representing 99% of the population of the community. Concentration exceeded maximum tolerable levels according to Spanish legislation in 95 towns; of these, the concentrations were over double the maximum value in 32, and in a further 18 municipalities the levels were over 150 mg/l. The consumption of these waters on the part of infants appears to be contraindicated, in view of the risk of meta-hemoglobinemia involved.

Cancer of the rectum in relation to components of the Spanish diet.

Cancer of the rectum is common in most industrialized countries. It is considered to be the result of a combination of environmental (diet, tobacco, alcohol, etc.) and genetic factors. We studied the evolution of morbidity and mortality due to cancer of the rectum and sigmoid in Spanish provinces and its relationship to different Spanish diet components. Our study covered the period 1977-1985. We used the indirect method to determine morbidity and mortality rates per 100,000 population, grouped according to age and sex. The consumption of different diet components was obtained from National Statistics Institute publications on the subject. These components were total lipids, animal fats, vegetable fats, butter and pork lard, margarine, fiber, and alcohol (all in g/person/day). For the study period, the mean national standardized mortality was 5.26 per 100,000 population and morbidity was 171.57 per 100,000. Provinces having rates above and below the national average were noted. The study revealed that, overall, alcohol consumption presents a 0.42 (p less than .001) positive correlation with standardized mortality, as does total lipid consumption.

[Chondrodysplasia punctata. 3 new cases and review of the Spanish literature]. / Condrodisplasia punctata. Tres nuevos casos y revisión de la literatura española.

Authors report three new cases of "chondrodysplasia punctata" two of them probably corresponding to Conradi-Hunerman's type and the third to rhizomelic type of Spranger. Series of cases published in Spain are reviewed. They conclude that clinic types of illness accepted according to Spranger (1971), in majority of spanish cases, have difficult application--own authors' opinion--because this differentiation does not solve clinic heterogeneity of illness. Genetics aspects of reviewed cases do not agree with expected and accepted results, probably because familiar antecedents were not well studied or genetics aspects are not yet well known.