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

Introducción: El deterioro intelectual y neurológico progresivo (DINP) en la infancia tiene una incidencia de 0,5 por mil nacimientos. Su impacto en lo que a morbimortalidad se refiere es importante. Los objetivos de este trabajo son conocer datos demográficos del DINP, su mortalidad y las principales causas que lo originan. Material y métodos: Se trata de un estudio retrospectivo y multicéntrico llevado a cabo en diferentes hospitales de la Comunidad Valenciana (España). Definición de caso: edad inferior a 18 años con pérdida de habilidades intelectuales o del desarrollo previamente adquiridas de al menos 3 meses de duración. Resultados: Participaron 9 hospitales y se reclutaron un total de 85 casos. La edad media al inicio de los síntomas fue de 1,8 años y al diagnóstico de 3,6. En el 68% de los casos existía un retraso previo al inicio de los síntomas. La mortalidad fue del 16,4%. Se llegó a un diagnóstico en el 74% de los casos. La causa más frecuentemente encontrada fue el síndrome de Rett. El 68% de los casos diagnosticados eran debidos a una metabolopatía. Discusión: La existencia de un retraso del desarrollo previo, así como el inicio tan precoz del proceso, puede dificultar la identificación de un DINP. Al igual que el resto de series, el mayor número de casos diagnosticados corresponde a metabolopatías. Conclusiones: El DINP en la infancia tiene un inicio precoz, con un amplio porcentaje de casos que permanecen sin diagnóstico etiológico y una mortalidad elevada (AU)

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 (AU)

[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.

Distonía hereditaria sensible a L-dopa secundaria a déficit de GTP ciclohidrolasa 1 / GTP cyclohydrolase 1-deficient dopa-responsive hereditary dystonia

La distonía sensible a L-dopa secundaria a déficit de GTP ciclohidrolasa 1 es una enfermedad con herencia autosómica dominante (AD) con penetrancia incompleta causada por mutaciones en el gen guanosina trifostato (GPT) ciclohidrolasa 1 (GTP-CH1). Se incluye dentro de los errores congénitos de los neurotransmisores, interviniendo en el metabolismo de la dopamina. Es la distonía con mejor respuesta al tratamiento con L-dopa. Presentamos el caso clínico de una niña de 7 años que inició un trastorno de la marcha causado por distonía del miembro inferior derecho, con empeoramiento a lo largo del día. Los estudios complementarios (laboratorio, neuroimagen) fueron normales. Se inició tratamiento de prueba con levodopa, con mejoría espectacular a dosis bajas. Estudio metabólico en LCR: niveles muy disminuidos de neopterina. El diagnóstico se confirmó genéticamente al encontrarse una mutación en el gen GTP-CH1 (p.W96X, cambio nucleótido c.287G>A). Después de un año de tratamiento con levodopa asociado a un inhibidor de decarboxilasa, existe resolución casi completa de síntomas sin efectos adversos (AU)

GTP cyclohydrolase 1-deficient dopa- responsive dystonia is an autosomal dominant disorder caused by mutations in the guanosine triphospate (GTP) cyclohydrolase 1 gene (GTPCH1) with incomplete penetrance. This gene is involved in the synthesis of dopamine. It is the dystonia with clinically significant response to levodopa within the group of neurotransmitter inborn errors. We report a case of seven years old female. Her initial symptoms were gait difficulties caused by right foot dystonia with aggravation of symptoms toward the evening. The laboratory studies and neuroimaging were normal. A therapeutic trial with levodopa was started with a dramatic response to low doses. Concentrations of total neopterin (NP) in cerebrospinal fluid (CSF) were reduced. Mutation analysis of the gene GCH1 confirmed the disease (p.W96X, nucleotide change c. 287G>A). After one year of levodopa therapy, we obtained maximum benefit with levodopa/decarboxylase inhibitor with absence of adverse effects (AU)

[GTP cyclohydrolase 1-deficient dopa-responsive hereditary dystonia]. / Distonía hereditaria sensible a L-dopa secundaria a déficit de GTP ciclohidrolasa 1.

GTP cyclohydrolase 1-deficient dopa- responsive dystonia is an autosomal dominant disorder caused by mutations in the guanosine triphospate (GTP) cyclohydrolase 1 gene (GTP-CH1) with incomplete penetrance. This gene is involved in the synthesis of dopamine. It is the dystonia with clinically significant response to levodopa within the group of neurotransmitter inborn errors. We report a case of seven years old female. Her initial symptoms were gait difficulties caused by right foot dystonia with aggravation of symptoms toward the evening. The laboratory studies and neuroimaging were normal. A therapeutic trial with levodopa was started with a dramatic response to low doses. Concentrations of total neopterin (NP) in cerebrospinal fluid (CSF) were reduced. Mutation analysis of the gene GCH1 confirmed the disease (p.W96X, nucleotide change c. 287G>A). After one year of levodopa therapy, we obtained maximum benefit with levodopa/decarboxylase inhibitor with absence of adverse effects.

Enfermedad de Graves-Basedow, celiaquía y síndrome de Down / Grave´s disease celiac disease and Down´s syndrome

Presentamos el caso de un niño de 11 años con síndrome de Down que padeció de forma simultánea enfermedad de Graves-Base-dow y celiaquía (AU)