[Total plasma homocysteine levels. Relationship with plasmatic folic acid levels and 677C T polymorphism of 5,10-methylenetetrahydrofolate reductase]. / Concentración plasmática de homocisteína: relación con los niveles plasmáticos de ácido fólico y con el polimorfismo 677C T de la 5,10-metilenotetrahidrofolato reductasa.

BACKGROUND: Moderately increased plasma homocysteine (Hcy) in children has been associated with stroke and venous thrombosis and with a parental history of cardiovascular disease (CVD). Evaluation of Hcy concentrations during childhood and study of the factors determining its concentrations could play an important role in the primary prevention of CVD. Objective To detect cases of hyperhomocystinemia and to examine the association between Hcy levels and plasma folic acid levels and 677C T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR). METHODS: The relationship between plasma Hcy levels, plasma folic acid levels, and the three genotypes of 677C T MTHFR polymorphism was investigated in 127 children (aged 2-18 years) and in 105 parents by multiple linear regression. RESULTS: The median Hcy levels were 5.00 mol/l in the children and 8.00 mol/l in the parents. Plasma folic acid levels were normal in all of the patients. The prevalence of the three genotypes in the children was 32.3 % for the CC genotype, 42.5 % for the CT genotype and 15.7 % for the TT genotype. Hcy concentrations were significantly higher in children with the TT genotype (p 0.018). Multiple linear regression revealed a positive direct effect of age (b 0.029, p 0.002) and a negative effect of genotype TT (b 3.886, p 0.002) on Hcy concentration. Hcy concentration was inversely correlated with folic acid levels but this correlation did not reach statistical significance. CONCLUSIONS: No cases of hyperhomocystinemia were found. To evaluate Hcy, age and plasma folic acid levels have to be taken into account in case there is a 677C T mutation. Hcy concentrations should be determined in older children with a family history of atherothrombosis and other risk factors for premature CVD.

Concentración plasmática de homocisteína: relación con los niveles plasmáticos de ácido fólico y con el polimorfismo 677 ct de la 5,10-metilenotetrahidrofolato reductasa / Total plasma homocysteine levels. Relationship with plasmatic folic acid levels and 677 CT polymorphism of 5,10-methylenetetrahydrofolate reductase

Antecedentes: El aumento moderado de la homocisteína plasmática en niños se ha relacionado con infartos cerebrales y trombosis venosas y con los antecedentes familiares de enfermedad coronaria prematura (ECP). La determinación de homocisteína en la infancia y el estudio de los factores que determinan su concentración podría ser importante para la prevención primaria de la ECP. Objetivo: Detectar algún caso de hiperhomocistinemia y valorar su relación con la concentración plasmática de ácido fólico y el polimorfismo 677C T de la 5,10-metilenotetrahidrofolato reductasa (MTHFR). Métodos: Se ha estudiado mediante la regresión lineal múltiple la relación entre la concentración plasmática de homocisteína, la del ácido fólico y los tres genotipos de la mutación 677C T de la MTHFR en 127 niños de entre 2 y 18 años y 105 de sus progenitores. Resultados: La concentración de homocisteína (mediana) fue de 5,00 y 8,00 mol/l en los niños y sus progenitores, respectivamente. Los valores plasmáticos de ácido fólico se encontraban todos en el rango de la normalidad. La prevalencia de los tres genotipos en los niños fue de 32,3% para el genotipo CC, 42,5% para el CT y 15,7% para el TT. La concentración de homocisteína era significativamente mayor con el genotipo TT (p = 0,018). En la regresión lineal múltiple se encontró un efecto directo positivo de la edad (b = 0,029; p = 0,001) y negativo del genotipo TT (b = -3,886; p = 0,002) sobre la concentración de homocisteína. El coeficiente de regresión de la concentración de ácido fólico aunque de signo negativo, no alcanzó significación estadística. Conclusiones: No se ha encontrado ningún caso de hiperhomocistinemia. Al valorar la homocisteína hay que tener en cuenta la edad y en caso de existir la mutación 677C T, los valores plasmáticos de ácido fólico. Sería conveniente determinar la homocisteína en los niños de mayor edad con antecedentes familiares de aterotrombosis y con otros factores de riesgo para la ECP (AU)

Pilot screening programme for cystinuria in the Valencian community.

Cystinuria is an autosomal recessive disorder of the kidneys and small intestine, affecting a luminal transport mechanism shared by cystine, ornithine, arginine and lysine. When cystine exceeds its solubility at low pH, the risk of stone formation increases. The data reported in the literature show a variation for the incidence of cystinuria, from 1 in 600 to 1 in 17,000, depending on the definition of cystinuria and the method used for screening the population. We set up a pilot screening programme to determine the incidence of cystinuria in the population of the Valencian Community. Urine filter paper samples submitted for the neonatal screening programme from 33,995 newborns (5-10 days old) were used for the study. Thin layer chromatography (TLC) was performed to screen cystinuric patients. To confirm positive filter paper samples, liquid samples were requested and TLC as well as the cyanide-nitroprusside test (CNT) were performed. Final diagnosis was achieved by quantifying cystine, lysine, ornithine and arginine using high-performance liquid chromatography (HPLC) in children's urine samples which remained positive for TLC and CNT for more than 1 year. We conclude that the incidence of subjects at risk for cystine stones in the Valencian Community is 1:1887. TLC is shown as a reliable method to perform newborn screening in large population to detect cystinuric subjects. Additional studies, including characterization of appropriate haplotypes, should be carried out for a more precise identification of the frequency of the different types of cystinuria in our population.

[Homocystinuria: effectiveness of the treatment with pyridoxine, folic acid, and betaine]. / Homocistinuria: eficacia del tratamiento con piridoxina, ácido fólico y betaína.

We present the results achieved with vitamin (pyridoxine and folic acid) and betaine (trimethyl-glycine) treatment of three patients with homocystinuria. Cases 1 and 2 were detected by having clinical findings suggestive of the disease (ocular and orthopedic alterations) and case 3 was diagnosed after a family metabolic screening was done. All presented a positive Brand's test and an abnormal elevation of plasma and urine homocysteine, as well as high methionine and low cystine levels in the plasma. Initially, when pyridoxine (600 mg/d) and folic acid (10 mg/d) were given for one month, a partial fall in the homocysteine levels was observed in cases 2 and 3, but not in case 1. When betaine was added (6 g/d), homocysteine disappeared from the plasma after the first month in cases 2 and 3, but only after the third month in case 1. Case 1 also showed a moderate clinical improvement in behavior and school performance. The treatment was maintained for two years in case 1, and for one year in cases 2 and 3. After betaine therapy, no disturbances were observed in the hepatic, renal and bone marrow functions, nor were there any clinically relevant ill-effects. These findings show that betaine offers a therapeutic alternative in the treatment of this disease, independent of the patient's response to pyridoxine.