[Total homocysteine levels in children with diabetes type 1. Conditional factors]. / Valores plasmáticos de homocisteína total en niños con diabetes mellitus tipo 1. Factores condicionantes.

OBJECTIVES: To measure the plasma levels of total homocysteine (tHcy) in children with type I diabetes mellitus and their relationship with the control of the disease. MATERIAL AND METHODS: We studied a total of 46 patients with ages between 4 and 19 years. The analyzed variables were: sex, age, puberty stage by Tanner, BMI, years of evolution of the illness, self-monitoring, associated diseases, tHcy, folic acid, vitamin B12, glycosylated haemoglobin (HbA1c), lipid profile and renal function. RESULTS: The mean tHcy was of 5.48 +/- 1,64 microm/l, similar to that in our control population. There was a positive correlation with tHcy when analyzing the puberty stage by the Tanner scale. The years of evolution of diabetes varied between 0.4 and 15, with a mean of 5.77 +/- 3.69, with no correlation with tHcy. The glycosylated haemoglobin mean was 7.35 %, with no correlation with tHcy. The levels of folic acid and vitamin B12 were similar to the control population. The lipid profile of our patients was normal, with no association with tHcy levels. There was no correlation between GFR and tHcy. CONCLUSIONS: A clinically correct control of children with diabetes mellitus type 1, appears to ensure a normal total homocysteinemia, with no significant differences with the healthy individuals of the same age and social environment.

Valores plasmáticos de homocisteína total en niños con diabetes mellitus tipo 1. Factores condicionantes / Total homocysteine levels in children with diabetes type 1. Conditional factors

Objetivos: Conocer las concentraciones plasmáticas de homocisteína total en niños afectados de diabetes mellitus tipo 1 y su relación con el control de la enfermedad. Material y métodos: Estudiamos un total de 46 pacientes con edades comprendidas entre los 4 y los 19 años. Las variables analizadas fueron: sexo, edad, estadio puberal de Tanner, índice de masa corporal, años de evolución de la enfermedad, autocontrol, patologías asociadas, homocisteína total (tHcy), ácido fólico, vitamina B12, hemoglobina glucosilada (HbA1c), perfil lipídico y función renal. Resultados: La homocisteína (Hcy) media fue de 5,48 ± 1,64 μm/l, similar a la de nuestra población control. Analizando el estadio puberal mediante la escala Tanner encontramos una correlación positiva con la Hcy. Los años de evolución de la diabetes oscilaban entre 0,4 y 15, con una media de 5,77 ± 3,69, sin correlación con la Hcy. La HbA1c media era del 7,35 %, sin correlación con la Hcy. Las concentraciones de ácido fólico y vitamina B12 fueron similares a la población control. El lipidograma de nuestros pacientes fue normal, sin relación con las cifras de Hcy. No hallamos correlación entre el índice de filtrado glomerular (GFR) y la Hcy. Conclusiones: Un correcto control clínico de los niños afectados de diabetes mellitus tipo 1 parece garantizar una homocisteinemia total normal, sin diferencias significativas con los individuos sanos de su misma edad y ambiente social (AU)

Objectives: To measure the plasma levels of total homocysteine (tHcy) in children with type I diabetes mellitus and their relationship with the control of the disease. Material and methods: We studied a total of 46 patients with ages between 4 and 19 years. The analyzed variables were: sex, age, puberty stage by Tanner, BMI, years of evolution of the illness, self-momitoring, associated diseases, tHcy, folic acid, vitamin B12, glycosylated haemoglobin (HbA1c), lipid profile and renal function. Results: The mean tHcy was of 5.48 ± 1,64 μm/l, similar to that in our control population. There was a positive correlation with tHcy when analyzing the puberty stage by the Tanner scale. The years of evolution of diabetes varied between 0.4 and 15, with a mean of 5.77 ± 3.69, with no correlation with tHcy. The glycosylated haemoglobin mean was 7.35 %, with no correlation with tHcy. The levels of folic acid and vitamin B12 were similar to the control population. The lipid profile of our patients was normal, with no association with tHcy levels. There was no correlation between GFR and tHcy. Conclusions: A clinically correct control of children with diabetes mellitus type 1, appears to ensure a normal total homocysteinemia, with no significant differences with the healthy individuals of the same age and social environment (AU)

Valores plasmáticos de homocisteína total en el recién nacido normal en el pretérmino. Factores condicionantes / Serum total homocysteine levels in normal and preterm newborn infants: conditioning factors

La hiperhomocisteinemia se ha involucrado en las enfermedades propias del embarazo y el parto, así como en las alteraciones fetales y del recién nacido. Para conocer el alcance real de este hecho y prevenir estas alteraciones, debemos conocer los valores normales de homocisteína total (tHcy) en los recién nacidos, tanto pretérmino como nacidos a término, y su relación con diversas variables que podrían influir en sus concentraciones. En este artículo mostramos que los niveles de tHcy están relacionados directamente con la edad gestacional y el peso de los recién nacidos

Hyperhomocysteinemis has been involved in health concerns associated with pregnancy and delivery and in fetal and neonatal anomalies. In order to determine the real implication of this fact and be able to prevent these alterations, we should know the normal values of serum total homocysteine (tHcy) in preterm and tern newborns and their relationship to different variables that could influence their concentrations. In this article, we show how tHcy levels are directly related to the gestational age and birthweight of infants

Tratamiento de la hiperfenilalaninemia por déficit de fenilalanina hidroxilasa con tetrahidrobiopterina. ¿Cuándo y cómo? / Tetrahydrobiopterin therapy for hyperphenylalaninemia due to phenylalanine hydroxylase deficiency. When and how?

Introducción: Algunos pacientes afectados de hiperfenilalaninemia por déficit de fenilalanina hidroxilasa responden con un descenso variable de las concentraciones plasmáticas de fenilalanina, a la administración por vía oral de tetrahidrobiopterina (BH4), de tal modo que pueden liberalizar o incluso abandonar la dieta con ingesta limitada de fenilalanina. Habitualmente, la identificación de los pacientes sensibles a BH4 se realiza mediante el test de sobrecarga con BH4, pero no existe acuerdo unánime con relación a su metodología e interpretación de los resultados. Desde esta perspectiva, es importante disponer de una herramienta que nos ayude a identificar del modo más sencillo posible a los pacientes tributarios de este tipo de tratamiento y conocer cuál es su evolución a largo plazo. Material y métodos: Se ha practicado el test de sobrecarga combinado de fenilalanina (100 mg/kg) y BH4 (20 mg/kg) en 20 pacientes con hiperfenilalaninemia sometidos a dieta limitada en fenilalanina. Resultados: Con independencia de su genotipo, la respuesta al test fue positiva en los 9 pacientes cuyo máximo nivel de fenilalanina al diagnóstico fue menor de 815 nmol/ml. Todos están en tratamiento con dosis de BH4 entre 7 y 15 mg/kg/día y en todos los casos ha sido posible aumentar notablemente la ingesta diaria de fenilalanina. En este momento 6 están con dieta libre, y los otros muy cerca de alcanzar este objetivo. Ninguno de los pacientes con un nivel de fenilalanina máximo al diagnóstico de más de 938 nmol/ml ha respondido al test de sobrecarga. Conclusiones: El nivel máximo de fenilalanina en el momento del diagnóstico, parece ser un método sencillo y fiable para predecir la respuesta al tratamiento con BH4. En los pacientes respondedores, el tratamiento continuado con BH4 permite la eliminación de la dieta limitada en fenilalanina en un alto porcentaje de casos

Introduction: Some patients with hyperphenylalaninemia due to phenylalanine hydroxylase deficiency respond with a variable decrease in plasma phenylalanine levels after oral tetrahydrobiopterin (BH4) administration and are then able to tolerate higher dietary phenylalanine intake or even to discontinue a phenylalanine-restricted diet. BH4-sensitive patients are usually identified by means of a BH4 loading test, but consensus on the methodology of this test and the interpretation of its results is lacking. Consequently, a simple tool to identify which patients are likely candidates for this treatment and how they will progress in the long-term is required. Material and methods: A combined oral BH4 loading test with phenylalanine (100 mg/kg) and BH4 (20 mg/kg) was performed in 20 patients with hyperphenylalaninemia under dietary phenylalanine restriction. Results: Independently of the genotype, the result was positive in all the 9 patients whose maximum phenylalanine level at diagnosis was below 815 nmol/ml. Currently, they are under treatment with tetrahydrobiopterin doses of 7-15 mg/kg/day. All these patients have been able to increase their oral phenylalanine intake. Six are currently following a normal diet and the remaining three are close to reaching this goal. None of the patients with a maximum phenylalanine level at diagnosis higher than 938 nmol/ml responded to the BH4 loading test. Conclusions: The maximum phenylalanine level at diagnosis seems to be a simple and reliable method to predict response to BH4 treatment. A high percentage of BH4-sensitive patients are able to discontinue a phenylalanine-restricted diet after long-term tetrahydrobiopterin treatment

[Severe fulminant form of neonatal citrullinemia. Report of a case]. / Forma grave fulminante de citrulinemia neonatal. Comunicación de un caso.

INTRODUCTION: Citrullinemia is an autosomal recessive disease, which is caused by a deficiency of the argininosuccinate synthetase. The neonatal forms are serious and many times are associated with a high level of mortality. CASE REPORT: A newborn that came in again on her third day of life due to a apneic episodes which required mechanical ventilation. Previously, she rejected feeding, had poor suction, lethargy and remarkable hypoactivity. During the following hours, she showed serious neurologycal deterioration with multifocal convulsions and coma, passing away 20 hours after admission due to endocraneal hypertension. The metabolic evaluation confirmed very significant hyperammonemia, with important increase of citrullin and glutamin, and arginine in the low limits of normality. She was treated with sodium benzoate and arginine and she also needed exanguinotransfusion. It was not possible to put her on hemodyalisis. The findings of the autopsy confirmed massive cerebral edema and characteristic hystological changes in the liver. The determination of the enzymatical activity in liver tissue showed a partial deficiency, with a residual activity of 25% of the average control. CONCLUSIONS: This is a case of fulminant neonatal citrullinemia that we considered of interest in order to draw the attention of the clinical on this type of diseases. The prognosis depends on early diagnosis, witch is based on clinical suspicion and analytical determination of ammonia in every newborn with unexplained vomiting, lethargy or other symptoms of encephalopathy.

[Oxidative phosphorylation defects with neonatal presentation: review of our caseload]. / Defectos de la fosforilación oxidativa de presentación neonatal: revisión casuística.

OBJECTIVES: To define the oxidative phosporilation deficit syndrome in the neonatal in terms of incidence and clinical, biochemical and genetic features. MATERIAL AND METHODS: We report 9 newborns diagnosed as oxidatic phosporilation deficit during the last 8 years in our hospital by means of clinical, metabolic, pathological and molecular studies, among other evaluations. The diagnosis was established based on ensymatic deficit of the respiratory chain, associated with alterations in the mtDNA in one case, and with mitochondrial ultrastructural anomalies in 5 cases. RESULTS: There was an incidence of 1/3.555 newborns and 1/832 newborns admitted in our Neonatal Unit. In four of them there were familial antecedents and polihidramnios in two. Most of them, 8 out of 9, were born at term after a normal pregnancy and delivery, with normal Apgar score and auxological examination. Symptomatology started immediately at the neonatal period as acute neurological damage in most of them. There was a severe evolution as 5 children died and 4 survived with severe damage. All of them had the classical phenotype of early severe encefalopathy, associated with dismorphic features, hypotomía, neurosensorial defects, brain dysgenesis and atrophy, anomalies in the EEG and in 5 of them there were also systemic anomalies, mainly cardiopathy. The most frequent biochemical alteration was a significative increment of the quotient lactate/piruvate. Five patients presented ultrastructural alterations of the mitochondria in thr muscle biopsy but Cox stain was not positive in any case. Three cases has a deficit of the complex IV, e of the complex I-IV, 2 of the complex I and one the complex I-III-IV. Only one patient had multiple deletions in the mtDNA. CONCLUSIONS: Oxidatic phosporilation deficit are frequent and severe diseases of prenatal onset with limited fetal effects, homogeneous clinical phenotype with frequent damage of the central nervous system and variable extraneurological alteration and inconsistent biochemical pattern. Enzymatic studies ar need for making the diagnosis in all suspected cases,

Defectos de la fosforilación oxidativa de presentación neonatal: revisión casuística / Oxidative phosphorilation defects with neonatal presentation: review of our experience

Objetivos: Definir el síndrome de déficit de la fosforilación oxidativa neonatal, en función de su incidencia, características perinatales, clínicas, bioquímicas y genéticas. Material y métodos : Se revisan los casos de 9 recién nacidos catalogados como déficit de la fosforilación oxidativa en los últimos 8 años en nuestro centro, mediante valoración clínica, metabólica, histopatológica, enzimática y molecular, además de otras evaluaciones. El diagnóstico se estableció en función del déficit enzimático de la cadena respiratoria, asociado a alteraciones del ADNmt en un caso, y en cinco a anomalías ultraestructurales mitocondriales. Resultados La incidencia fue de 1/3.555 y de 1/832 recién nacidos ingresados en nuestra unidad neonatal. Cuatro tenían antecedentes familiares positivos, y dos polihidramnios. La mayoría (8/9) fueron recién nacidos a término, de embarazo y parto normales, con Apgar y somatometría también normales. La clínica se inició en el período neonatal inmediato, como sufrimiento neurológico agudo en la mayoría. La evolución fue grave (5 fallecieron y 4 sobreviven gravemente afectados). Todos presentaban un fenotipo clínico de encefalopatía grave precoz, asociada a dismorfia, hipotonía, alteraciones neurosensoriales, atrofia y disgenesia cerebral, electroencefalograma patológico, y en 5 de ellos, además, a anomalías viscerales (principalmente cardiopatía). La alteración bioquímica más frecuente fue un aumento significativo del cociente lactato/piruvato. Cinco pacientes presentaron alteraciones ultraestructurales mitocondriales en la biopsia muscular pero la tinción de Cox no resultó claramente patológica en ningún caso. Tres tenían un déficit del complejo IV, tres de I-IV, dos del I y uno del I-III-IV. Sólo en un paciente se detectaron deleciones múltiples del ADNmt. Conclusiones Se trata de enfermedades frecuentes y graves, de comienzo prenatal con escasa repercusión fetal, fenotipo clínico homogéneo con afectación predominante del SNC y extraneurológica variable, y perfil bioquímico inconstante. El diagnóstico exige el estudio enzimático de la cadena respiratoria en todos los casos sospechosos (AU)