Sospecha clínica y estudios diagnósticos iniciales en enfermedades metabólicas hereditarias / Clinical suspicion and initial diagnostic studies in inherited metabolic diseases

Las enfermedades metabólicas hereditarias (EMH) constituyen un grupo diverso y complejo de trastornos genéticos que, aunque individualmente son poco frecuentes, en su conjunto representan una importante causa de morbilidad y mortalidad. Se lleva a cabo una revisión exhaustiva de la literatura con el objetivo de proporcionar información que oriente la sospecha clínica y el enfoque en los estudios diagnósticos iniciales, cuya clave reside en una anamnesis completa que abarque los antecedentes familiares y obstétricos, junto con una consideración cuidadosa de las manifestaciones clínicas del paciente. Es crucial tener en cuenta la naturaleza multisistémica de estas enfermedades que pueden manifestarse desde el periodo neonatal, generalmente como intoxicaciones agudas, hasta una presentación más insidiosa en adultos jóvenes. Si la evaluación clínica sugiere la posibilidad de una EMH, es fundamental llevar a cabo medidas de apoyo general y realizar investigaciones de laboratorio de manera simultánea. En neonatos, donde la presentación de una EMH puede representar una emergencia médica que requiere una respuesta inmediata, esta acción es especialmente crítica. El diagnóstico de las EMH representa un desafío debido a su variabilidad clínica y sintomatología heterogénea. Sin embargo, la identificación temprana de estas enfermedades es fundamental para iniciar un tratamiento oportuno y mejorar el pronóstico de los pacientes.(AU)

Inherited metabolic diseases (IMDs) constitute a diverse and complex group of genetic disorders that, although individually rare, collectively represent a significant cause of morbidity and mortality. A comprehensive literature review is carried out with the aim of providing information to guide clinical suspicion and the approach to initial diagnostic studies, the key of which lies in a complete medical history encompassing family and obstetric backgrounds, along with careful consideration of the patient’s clinical manifestations. It is crucial to consider the multisystemic nature of these diseases, which can manifest from the neonatal period, usually as acute intoxications, to a more insidious presentation in young adults. If clinical evaluation suggests the possibility of an IMD, it is essential to implement general supportive measures and simultaneously perform laboratory investigations. In neonates, where the presentation of an IMD can represent a medical emergency requiring an immediate response, this action is especially critical. The diagnosis of IMDs poses a challenge due to their clinical variability and heterogeneous symptomatology. However, early identification of these diseases is crucial for initiating timely treatment and improving patient prognosis.(AU)

[Nutrition and Metabolism Group of the Spanish Neonatology Society: recommendations and evidence for dietary supplementation with probiotics in very low birth weight infants]. / Grupo de Nutrición y Metabolismo Neonatal, Sociedad Española de Neonatología: recomendaciones y evidencias para la suplementación dietética con probióticos en recién nacidos de muy bajo peso al nacer.

Clinical practice guidelines are an important tool for improving healthcare. In recent years there has been accumulating evidence on the impact of nutritional supplementation with probiotics in the very low birth weight infants. With no uniformity in microorganisms and strains used. The Spanish Neonatology Society (SENeo), through its Nutrition and Metabolism Group has undertaken to develop recommendations that will be useful as a guide for the neonatologist in this field.

[Ante-natal corticosteroids and prevention of respiratory distress in the premature newborn: usefulness of rescue treatment]. / Corticoides antenatales y prevención del distrés respiratorio del recién nacido prematuro: utilidad de la terapia de rescate.

The effectiveness of antenatal corticosteroid therapy for foetal lung maturation in pre-term infants is well known, but there is uncertainty about the time that the treatment remains effective. A descriptive, longitudinal study was conducted to determine whether the need for surfactant administration was determined by the time-lapse between corticosteroids administration and delivery, and when repeating the doses of maternal corticosteroids should be considered. A total of 91 premature infants ≤32 weeks and/or ≤1,500 g (limit 34+6 weeks) whose mothers had received a complete course of corticosteroids were included. In patients at 27-34+6 weeks, we found that the longer the time elapsed between delivery and administration of corticosteroids, most likely were the babies to require treatment with surfactant (P=.027). The resulting ROC curve determined an 8-days cut-off after which repeating a dose of corticosteroids should be assessed.

Meduloblastoma congénito gigante de presentación y localización atípicas / Congenital giant medulloblastoma with atypical presentation and location

El meduloblastoma congénito es uno de los tumores intracraneales más frecuentes en la edad pediátrica; sin embargo, su presentación es poco frecuente antes de los 2 meses de vida. Presentamos el caso deun recién nacido con un meduloblastoma congénito gigante, con sintomatología en el periodo neonatal inmediato y de localización atípica. Este tipo de tumor debe ser tenido en consideración al realizar el diagnóstico diferencial de la hidrocefalia congénita (AU)

Congenital medulloblastoma is one of the most frequent pediatric intracranial tumors, however, it is unusual its presentation before the two months of life. We are presenting the case of a new-born infant with a giant congenital medulloblastoma, with symptoms in the immediate neonatal period and atypical location. This kind of tumor must be taken on account when making a differential diagnosis of congenital ventricular hydrocephalus (AU)

¿Mejora el aporte proteico precoz el crecimiento extrauterino en recién nacidos pretérmino de bajo peso? / Does early parenteral protein intake improve extrauterine growth in low birth weight preterms?

Introducción: El retraso de crecimiento postnatal es frecuente en los recién nacidos pretérmino (RNPT) de bajo peso. La administración precoz de proteínas en su nutrición parece mejorar el crecimiento extrauterino y las comorbilidades asociadas. Evaluamos el impacto sobre el crecimiento posnatal de un nuevo protocolo de nutrición parenteral con aporte precoz de aminoácidos en recién nacidos < 1.500g. Material y métodos: Estudio observacional de casos-controles sobre una muestra de 58 RNPT < 1.500g. El grupo de casos lo formaron 29 RNPT que recibieron al menos 1,5g/kg/día de aminoácidos vía parenteral en las primeras 24h de vida, con aumentos diarios hasta alcanzar al menos 3,5g/kg/día al 3.°-4.° día, comparándose con un grupo control de 29 RNPT en los que el aporte de aminoácidos se inició el 2.°-3.° día de vida a 1g/kg/día, con incrementos menores diariamente. Valoramos la evolución somatométrica de ambos en el primer mes de vida. Resultados: No había diferencias en las características basales (sexo, edad gestacional, parámetros somatométricos) entre ambos grupos. Los RNPT que recibieron proteínas a dosis mayores y más precozmente tuvieron una ganancia de peso significativamente mayor que el grupo control (423±138g vs. 315±142g; p=0,005), presentando también una mayor velocidad de ganancia ponderal diaria (19,4±3,3 vs. 16,5±4,8; p=0,010) y una recuperación más precoz del peso al nacimiento (11,5±3,3 días vs. 14,5±4,5 días; p=0,045). No se observó mayor incidencia de complicaciones. Conclusiones: El aporte precoz de aminoácidos a dosis más altas mejora la ganancia ponderal en RNPT sin observarse un riesgo añadido para el paciente(AU)

Introduction: Extrauterine growth restriction affects most premature newborns. Early and higher parenteral protein intake seems to improve postnatal growth and associated comorbidities. We evaluate the impact of a new parenteral nutrition protocol based on early amino acid administration on postnatal growth in premature infants with a birth weight < 1,500 grams. Material and methods: A case-control study in 58 premature newborns with a birth weight < 1,500 grams. In the case group we included 29 preterm neonates who received at least 1.5g/kg/day parenteral amino acid during the first 24hours after birth, reaching a maximum dose of 3.5g/kg/day on the 3rd-4th day after birth. The control group was formed by 29 preterm neonates for whom protein support began on the 2nd-3rd day after birth with a dose of 1g/kg/day with lower daily increases than the case group. Growth rates and complications were followed until 28 days of life or discharge from NICU. Results: There were no differences between groups in baseline characteristics. Premature newborns who received higher and earlier doses of proteins had a greater weight gain than the control group, and this difference was statistically significant (423±138g vs. 315±142g; P=.005). In addition, they had a higher daily weight gain rate (19.4±3.3 vs. 16.5±4.8; P=.010) and they regained birth weight earlier (11.5±3.3 days vs. 14.5±4.5 days; P=.045). A higher incidence of complications was not observed. Conclusions: Early and higher amino acid administration improves growth rate in premature neonates with no apparent increase in risks for the patient(AU)

Trombosis intracardiaca neonatal ligada a catéter: utilidad del activador tisular del plasminógeno recombinante / Neonatal intracardiac thrombosis related to catheter: use of recombinat tissue plasminogen activator

La utilización de catéteres venosos centrales en las unidades de cuidados intensivos neonatales es una práctica habitual no exenta de complicaciones. Dentro de dichas complicaciones, las más frecuentes son las de tipo infeccioso, aunque no podemos desdeñar las de tipo mecánico y trombótico. La incidencia de trombosis ligada al catéter es variable, y la actitud que cabe tomar ante dicho cuadro sigue siendo controvertida en el periodo neonatal. Presentamos el caso de un recién nacido a término que, debido a su patología de base, precisó un acceso venoso central mediante canalización umbilical. Al tercer día de vida se detectó por ecocardiografía la existencia de un trombointra auricular derecho, que se resolvió mediante tratamiento fibrinolítico local con activador tisular del plasminógeno recombinante, administrado a través de catéter silástico central, sin observarse complicaciones mayores(AU)

The use of central venous catheters in the intensive neonatal care units is a common practice not without complications, being infections its most common type, although mechanic and thrombotic ones are also common. The incidence of thrombosis related to catheter varies, and the attitude in the neonatal period remains controversial. We are discussing a case of a term new born suffering from a previous pathology, and central venous access via umbilical pipe was required. On its third day of life, the newborn was detected a right a trial thrombus by means of echocardiography, that was resolved with local thrombolytic therapy with r TPA, administered through central silastic catheter with no further complications observed(AU)

Hipermetioninemia en el recién nacido pretérmino. Estudio de los factores predisponentes / Hypermethioninemia in the preterm newborn. Predisposing factors

Introducción: El exceso de metionina puede ser causa de alteraciones del sistema nervioso central, tales como edema cerebral difuso y trastornos de la mielinización. Pacientes y método: Estudio ambispectivo observacional durante un período de 15 meses de los recién nacidos prematuros ingresados en nuestro hospital que presentaron hipermetioninemia en las pruebas de cribado neonatal por espectrometría de masas en tándem. Seguimiento evolutivo de estos neonatos hasta el año de edad con valoración de sus niveles de metionina en relación con la alimentación, parámetros somatométricos y desarrollo neurológico. Resultados: De una población de estudio de 187 neonatos pretérmino, 16 de ellos presentaron hipermetioninemia aislada. El peso y la alimentación de estos recién nacidos con una fórmula de inicio especial enriquecida en metionina está relacionada con el aumento del número de casos de hipermetioninemia aislada transitoria (el 62,6% recibieron un aporte de metionina superior a 97mg/kg/día), además se halló una correlación estadísticamente significativa entre los días que los pacientes recibían esa fórmula y el tiempo que tardaron en normalizarse las cifras de metionina en plasma (r: 0,791; p: 0,000). No observamos correlación entre las cifras máximas de metionina alcanzadas en plasma y la puntuación obtenida en el test de Brunet Lézine a los 6 meses de edad corregida. Conclusiones: Este estudio pone de relevancia la importancia del suplemento de aminoácidos, concretamente de metionina, en las leches de fórmula de los recién nacidos prematuros por la trascendencia que pueden suponer para su desarrollo neurológico (AU)

Introduction: Excess methionine can cause central nervous system disorders such as diffuse cerebral edema and disorders of myelin. Patients and method: A retrospective and prospective (ambispective) observational study in preterm newborns admitted to our hospital over a period of 15 months and who had hypermethioninemia in neonatal screening tests by tandem mass spectrometry. The progress of these infants was monitored during the first year of life, assessing their methionine levels, diet, somatometric parameters and neurodevelopment. Results: From a study population of 187 preterm infants, 16 of them showed isolated hypermethioninemia. Weight and feeding the babies with a special formula enriched with methionine is related to an increased number of cases of transient isolated hypermethioninemia (62.6% received a higher contribution of methionine than 97mg/kg/day). We also found a statistically significant correlation between the days that patients received the formula and the time it takes to normalize the levels of methionine in plasma (R 0.791, p=0.000). There was no correlation between the methionine peak reached in plasma and the score on the Brunet Lézine test, at the corrected age of 6 months. Conclusions: This study highlights the importance amino acid supplements, particularly methionine, in premature infants’ formulas due to the impact they may have on neurological development (AU)

[Hypermethioninemia in the preterm newborn. Predisposing factors]. / Hipermetioninemia en el recién nacido pretérmino. Estudio de los factores predisponentes.

INTRODUCTION: Excess methionine can cause central nervous system disorders such as diffuse cerebral edema and disorders of myelin. PATIENTS AND METHOD: A retrospective and prospective (ambispective) observational study in preterm newborns admitted to our hospital over a period of 15 months and who had hypermethioninemia in neonatal screening tests by tandem mass spectrometry. The progress of these infants was monitored during the first year of life, assessing their methionine levels, diet, somatometric parameters and neurodevelopment. RESULTS: From a study population of 187 preterm infants, 16 of them showed isolated hypermethioninemia. Weight and feeding the babies with a special formula enriched with methionine is related to an increased number of cases of transient isolated hypermethioninemia (62.6% received a higher contribution of methionine than 97mg/kg/day). We also found a statistically significant correlation between the days that patients received the formula and the time it takes to normalize the levels of methionine in plasma (R 0.791, p=0.000). There was no correlation between the methionine peak reached in plasma and the score on the Brunet Lézine test, at the corrected age of 6 months. CONCLUSIONS: This study highlights the importance amino acid supplements, particularly methionine, in premature infants' formulas due to the impact they may have on neurological development.

Serum levels of IGF1 are a useful predictor of retinopathy of prematurity.

OBJECTIVE: To ascertain whether insulin-like growth factor 1 (IGF1) is associated with retinopathy of prematurity (ROP) and is a useful predictor of the disease. Although its aetiopathogenesis is multifactorial, development of the disease appears to be related to a deficiency in IGF1, a hormone that acts together with vascular endothelial growth factor in the normal angiogenesis in the retina. DESIGN: Prospective study for a 30-month period. PARTICIPANTS: A total of 74 premature newborn babies, of less than 1500 g and/or 32 weeks' gestational age or less. TESTING: To determine the development and severity of ROP. MAIN OUTCOME MEASURES: Serum levels of IGF1 were measured once a week from birth until 40 weeks corrected gestational age in each subject. RESULTS: Of our subjects, 32.4% developed some form of ROP, and all those ROP patients had the following characteristics at birth (median +/- standard deviation scores): low weight (1098 +/- 188 vs. 1393 +/- 285 g), short length (36.74 +/- 1.77 vs. 38.89 +/- 3.08 cm), small cranial perimeter (26.03 +/- 1.74 vs. 27.93 +/- 1.81 cm) and young gestational age (29.7 +/- 1.78 vs. 31.3 +/- 1.79 weeks) (p < 0.05). Other factors previously associated with ROP that were also observed with statistically significant frequency in our ROP patients were bronchopulmonary dysplasia, intracranial haemorrhage, the need for erythrocyte transfusion or treatment with erythropoietin and sepsis (all p < 0.05). Levels of IGF1 at the 3rd week post-partum, independent of gestational age at birth, were clearly lower in the group who developed ROP (29.13 vs. 43.16 ng/mL, p < 0.05). A value of 30 ng/mL of IGF1 in the third week post-partum was found to have a 90% sensitivity in the diagnosis of ROP. A rapid rise in IGF1 levels between the 3rd and 5th weeks appeared to be related to the development of a higher stage of ROP. CONCLUSION: Determination of IGF1 serum levels in the 3rd week post-partum, independent of gestational age at birth, provides a sufficient and reliable prognostic tool and allows the identification of a group of patients at high risk of developing the disease.

Perspectivas actuales en el tratamiento del hiperinsulinismo congénito / Current views on the therapeutic management of congenital hyperinsulinism

El hiperinsulinismo congénito (HIC) engloba a un grupo de entidades clínica, genética y morfológicamente heterogéneas, que presentan en común una hipoglucemia persistente hipocetósica asociada a valores inapropiadamente elevados de insulina para dichos estados de hipoglucemia. Su diagnóstico se realiza, en muchas ocasiones, demasiado tarde y de forma incompleta debido, entre otras razones, al desconocimiento acerca de esta rara enfermedad, a su resolución muchas veces mortal antes del diagnóstico, a la expresividad altamente variable y heterogénea, que dificulta el diagnóstico, y a una incorrecta clasificación histopatológica de la enfermedad. Sin embargo, el conocimiento reciente de las bases moleculares de esta enfermedad en nuestro país abre un nuevo abanico de posibilidades diagnósticas y terapéuticas. En el presente trabajo queremos proponer un esquema global de actuación para el tratamiento de esta enfermedad, intentando resumir los conocimientos clínicos y moleculares de los que se dispone hasta el momento, de manera que pueda servir como guía básica para los pediatras que se encuentren en su práctica clínica ante un caso de HIC. El propósito fundamental es contribuir a mejorar tanto el diagnóstico como el pronóstico y el tratamiento de esta enfermedad en nuestro país (AU)

Congenital hyperinsulinism comprises a group of clinically, genetically and histopathologically heterogeneous entities; however, all of them coincide in that the patients have recurrent and persistent hypoketotic hypoglycemia associated withab normally elevated insulin levels. It is often diagnosed toolate and employing inadequate means due to, among other reasons, the ignorance with regard to this uncommon disease, the high rate of mortality prior to diagnosis, the wide heterogeneity of the clinical symptoms and treatment responses that make the diagnosis difficult and, in all probability, an erroneous histopathological classification of the disease. However, the recent knowledge of the molecular basis of this disease in Spain opens up new diagnostic and therapeutic possibilities. In the present review, we propose an overall strategy for the therapeutic management of this disease, summarizing the clinical and molecular concepts available to date, which could serve as basic guidelines for any pediatrician treating a patient with congenital hyperinsulinism. Thus, we attempt to improve the clinical management of this disease in Spain (AU)

[Importance of early diagnosis and treatment in the prognosis of type I Glutaric Acidaemia]. / Importancia del diagnóstico precoz y el tratamiento temprano en el pronóstico de la aciduria glutárica tipo I.

INTRODUCTION: Glutaric Acidaemia type I (GA-I) is an autosomal recessive progressive neurodegenerative inborn error of metabolism caused by deficient activity of the enzyme glutaryl-CoA dehydrogenase (GCDH). In most cases, the diagnosis is established biochemically by the detection of glutaric acid and 3-hydroxy glutaric acid in urine and glutarylcarnitine in plasma. Patients excreting small amounts of glutaric acid may be overlooked. OBJECTIVE: To investigate the value of expanded newborn screening by adding the measurement of urine glutarylcarnitine to conventional chromatography-mass spectrometry (GC-MS) in the diagnosis of GA-1. MATERIAL AND METHODS: We report clinical and biochemical data in 5 GA-I patients diagnosed in our Hospital. Details regarding biochemical diagnosis are emphasised and the absence or presence of symptoms was correlated with neuroimaging findings, age at diagnosis and treatment. RESULTS: Two patients showed high glutarylcarnitine levels in plasma and were identified by routine newborn GC-MS screening. Following early appropriate treatment they are asymptomatic 6 years later. Two patients with delayed diagnosis displayed neurological sequels in spite of treatment. The remaining patient, who presented with encephalopathic episode at age 8 months showed normal glutarylcarnitine levels in routine plasma GC-MS but high urine glutarylcarnitine levels in a retrospectively screened urine sample from the newborn period. CONCLUSIONS: Early treatment seems to positively influence the clinical evolution of GA-I patients. Thus, improving the identification of GA-I represents an important diagnostic challenge. The urinary excretion of glutarylcarnitine is a specific biochemical marker of GA-I and allows the identification of patients without glutaric aciduria and with normal plasma acylcarnitine profiles.

Importancia del diagnóstico precoz y el tratamiento temprano en el pronóstico de la aciduria glutárica tipo I / Importance of early diagnosis and treatment in the prognosis of type I gluraric acidaemia

Introducción. La aciduria glutárica tipo I (AG-I) es un desorden metabólico de herencia autosómica recesiva y carácter progresivo debido al déficit de la enzima glutaril-CoA-deshidrogenasa (GCDH). El diagnóstico se realiza generalmente por una elevación del ácido glutárico y 3-hidroxiglutárico en la orina y de la glutarilcarnitina en el plasma. Existen casos falsos negativos en relación con la baja tasa excretora del ácido glutárico. Objetivo. Resaltar la importancia de la ampliación del cribado neonatal por espectrofotometría de masas en tándem (MS/MS) mediante la inclusión de la medición de glutarilcarnitina en la orina para su diagnóstico. Material y métodos. Se aportan los datos clínicos y el perfil bioquímico que llevaron al diagnóstico en 5 pacientes diagnosticados de AG-I en nuestro centro. Se analiza la evolución clínica y de neuroimagen en función de la edad, el diagnóstico y el inicio del tratamiento. Resultados. Dos casos de diagnóstico por cribado convencional mediante MS/MS siguieron un tratamiento precoz y están asintomáticos 6 años después. Dos pacientes de diagnóstico y tratamiento tardíos presentan secuelas neurológicas. El último paciente, diagnosticado a los 8 meses tras una presentación aguda encefalopática, mostraba valores de glutarilcarnitina en plasma en rango normal, mientras que el análisis retrospectivo de la orina del período neonatal reveló valores elevados de glutarilcarnitina. Conclusiones. El tratamiento temprano parece asociarse a una evolución neurológica favorable en pacientes con AG-I, por lo que su identificación precoz constituye un reto diagnóstico. La excreción urinaria de glutarilcarnitina es un marcador específico de AG-I y permite la identificación de pacientes sin aciduria glutárica y valores normales de glutarilcarnitina en sangre

Introduction. Glutaric Acidaemia type I (GA-I) is an autosomal recessive progressive neurodegenerative inborn error of metabolism caused by deficient activity of the enzyme glutaryl-CoA dehydrogenase (GCDH). In most cases, the diagnosis is established biochemically by the detection of glutaric acid and 3-hydroxy glutaric acid in urine and glutarylcarnitine in plasma. Patients excreting small amounts of glutaric acid may be overlooked. Objective. To investigate the value of expanded newborn screening by adding the measurement of urine glutarylcarnitine to conventional chromatography-mass spectrometry (GC-MS) in the diagnosis of GA-1. Material and methods. We report clinical and biochemical data in 5 GA-I patients diagnosed in our Hospital. Details regarding biochemical diagnosis are emphasised and the absence or presence of symptoms was correlated with neuroimaging findings, age at diagnosis and treatment. Results. Two patients showed high glutarylcarnitine levels in plasma and were identified by routine newborn GC-MS screening. Following early appropriate treatment they are asymptomatic 6 years later. Two patients with delayed diagnosis displayed neurological sequels in spite of treatment. The remaining patient, who presented with encephalopathic episode at age 8 months showed normal glutarylcarnitine levels in routine plasma GC-MS but high urine glutarylcarnitine levels in a retrospectively screened urine sample from the newborn period. Conclusions. Early treatment seems to positively influence the clinical evolution of GA-I patients. Thus, improving the identification of GA-I represents an important diagnostic challenge. The urinary excretion of glutarylcarnitine is a specific biochemical marker of GA-I and allows the identification of patients without glutaric aciduria and with normal plasma acylcarnitine profiles

[Advances in the diagnosis and treatment of maple syrup urine disease: experience in Galicia (Spain)]. / Avances en el diagnóstico y tratamiento de la enfermedad de jarabe de arce, experiencia en Galicia.

INTRODUCTION: Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder caused by an inherited deficiency of branched chain alpha-ketoacid dehydrogenase activity. Accumulation of the amino acids leucine, isoleucine, valine and alloisoleucine and their metabolic products in cells and biological fluids results in severe brain dysfunction. PATIENTS AND METHODS: We present three cases of MSUD diagnosed in Galicia since 2000, the year in which the Extended Newborn Screening Program by tandem mass spectrometry was started in this region. One of the patients was diagnosed on the basis of early clinical presentation and the others by neonatal screening. Enzymatic and molecular studies confirmed two classic cases of MSUD and an intermediate variant. We describe the clinical and biochemical details at confirmation of diagnosis and the long-term outcome of the three patients. Throughout follow-up, all the patients maintained adequate leucine levels, which were near the normal range (mean levels: 220, 177 and 252 micromol/L, respectively). Several moderate metabolic decompensations were observed but leucine levels only occasionally exceeded 1000 micromol/L (one day in two patients). IQ tests were performed in all patients and scores were within the normal range. In view of our results, we believe the following measures are essential to improve the prognosis of MSUD: inclusion of this disease in Expanded Neonatal Screening Programs with early samples (at 2-3 days of life); aggressive treatment in the initial phase and during acute decompensations; strict metabolic control to prevent crises, monitoring of branched-chain amino acids (dried blood spot sample), and maintenance of long term plasma leucine levels below 300 micromol/L.

Avances en el diagnóstico y terapéutica de los niños con tirosinemia tipo I / Advances in the diagnosis and treatment of children with tyrosinemia type I

La tirosinemia Tipo I es un error genético del metabolismode la tirosina producido por un déficit deFumarilacetoacetato Hidrosilasa (FAH), último enzimaen la vía de degradación de la tirosina, que dalugar al acúmulo de metabolitos intermediarios maleily fumaril-acetoacetato produciendo toxicidad hepáticay renal, y el metabolito secundario succinilacetona,produciendo efectos sistémicos y locales.Se suele presentar como hepatopatía aguda o crónicay/o carcinoma hepatocelular, disfunción tubularrenal o manifestaciones neurológicas. Como alternativasterapéuticas en el momento actual destacarel tratamiento dietético, la terapia con NTBC (2-(2-Nitro-4-trifluorometilbenzoil) 1-3-ciclohexanodiona) yel trasplante hepático. Este último se reserva básicamentepara pacientes con mala respuesta alNTBC, riesgo de malignidad y/o mala calidad de vidacon las otras alternativas terapéuticas. Presentamos3 casos de pacientes que han recibido NTBCde forma precoz con muy buena respuesta clínica ybioquímica, como muestra del importante cambioque se ha producido en los últimos años en esta enfermedad,lo que conlleva a grandes mejoras tantoen la calidad de vida como en su pronóstico

Tyrosinemia type I is a inborn error of tyrosinemetabolism caused by a deficiency of fumarylacetoacetase(FAH), the last enzyme in the tyrosine catabolicpathway; as a result, the reactive compoundsmaleylacetoacetate and fumarylacetoacetate are formed,which are thought to be responsable for the liverand kidney injury, and the secondary metabolitesuccunylacetone, with regional and general injurys.Clinically the disorder is characterised by progressiveacute or chronic liver damage and/or hepatocellularcarcinoma, renal tubular dysfunction or neurologicalcrises. The current therapy includes dietaryrestriction, NTBC (2-(2-nitro-4-trifluoromethyl benzoyl)-1-3-cyclohexanedione) therapy and liver transplantation.The indications for liver transplantationinclude non-response to NTBC, risk of malignancyand poor quality of live related to the other therapies.Here we report 3 patients early managed with NTBCresulting in clinical and biochemical improvement, toshow the important changes in the managenent ofthe disease in the last years, with better quality of lifeand pronostic as a result