Condrodisplasia «punctata» rizomélica clásica: comunicación de dos casos con las formas grave y benigna de la afección / Classic rhizomelic chondrodysplasia punctata: report of 2 cases with two forms of the disease

La condrodisplasia punctata rizomélica clásica (RCDP) es una rara enfermedad multisistémica autosómica recesiva, debida a una alteración del metabolismo peroxisomal que determina una deficiencia de la biosíntesis de plasmalógenos y de la alfaoxidación del ácido fitánico. Se caracteriza por la presencia desde el nacimiento de un acortamiento proximal de las extremidades, calcificaciones periarticulares, dismorfia facial, retraso del desarrollo y mortalidad precoz. Se presentan dos casos de RCDP clásica, o tipo I, con las dos formas clínicas de presentación, grave o mortal y leve o benigna, en relación con la existencia de actividad enzimática residual, y se revisan sus principales aspectos clínicos(AU)

Classic rhizomelic chondrodysplasia punctata (CRCP) is a rare multisystem disease, autosomal recessive disorder. It is due because a peroxisomal metabolism alteration that determine deficiency of the plasmalogen biosynthesis and the alpha oxidation of phytanic acid. It is characterized by proximal shortening of the limbs, punctuate calcifications of the epiphyses, facial dysmorphia, developmental delay and early lethality. We present two cases of CRCP type I with two different forms of presentation, one severe and another one mild or bening, in relation with the residual enzyme activity and we revise the main clinical aspects(AU)

Hiperinsulinimso neonatal por nueva mutación del gen ABBCC8 con evolución hacia diabetes hipoinsulínica / Neonatal hyperinsulinism due to new mutation of ABCCS gene with evolution towards hypoinsulinemic diabetes

Recientemente se han descrito mutaciones activadoras de los genes ABCC8 y KCNJ11 causantes de hiperinsulinismo hipoglucémico seguido del desarrollo de una diabetes hipoinsulínica posterior. Se presenta un caso de hiperinsulinismo congénito neonatal por nueva mutación el gen ABCC8 con evolución hacia una diabetes hipoinsulínica al cabo de cuatro caos de evolución. Se trata de una recién nacida macrosómica afecta de hiperinsulinismo con una expresión clínica importante ya que inicialmente presentaba hipoglucemias e hiperinsulinemias severas con buena respuesta al diazóxido. Posteriormente fue estabilizándose la situación metabólica, llegando a retirarse la medicación sin apenas recaídas importantes. A continuación y coincidiendo con procesos infecciosos intercurrentes, se apreciaba tendencia a descender las glucemias sin llegar a presentar hipoglucemias e hiperinsulinemias francas y sin cetosis, que no respondieron a la medicación. Finalmente, a los cinco años de edad aparece una intolerancia a la glucosa con hiperglucemias postprandiales y una sobrecarga oral de glucosa patológica indicativa de una evolución a diabetes mellitus hipoinsulínica. Se detectó la mutación Thr1515Ala en heterocigosis en el exón 37 del gen ABCC8 responsable de la codificación de la proteína SUR1 que no hemos encontrado descrita en la literatura revisada. Se discute el posible mecanismo por la cual se pasa de un estado de hiperinsulinismo hipoglucémico a hipoinsulinismo o diabetes hipoinsulínica (AU)

The have been described recently activating mutations in ABCC8 and KCNJ11 genes that are related wyth hypoglycemic hyperinsulinism that subsequently change to hypoinsulinemic diabetes. We present a case of congenital neonatal hyperinsulinism caused by a new mutation in ABCC8 gene that changed to a hypoinsulinemic diabetes after 4 years of evolution. A macrosomic female newborn with severe hypoglycaemia and hyperinsulinemia with good response to diazoxide was followed in our Unit. Subsequently the patient remains compensated and the medication could be discontinued without symptoms of relapses of hypoglycaemia. Along the period of evolution and when the patient suffered intercurrent infectious episodes she showed tendency to present with low glycemia but without of documented hypoglycaemia, hyperinsulinemia or ketosis that did not respond to medication. When she was 5 years old the patient developed glucose intolerance with postprandial hyperglycaemia nad with an oral glucose tolerance curve compatible with hypoinsulinemic diabetes mellitus. Genetic analysis showed Thr1515Ala mutation in heterozygosis in exon 37 of the ABCC8 gene responsible of coding SUR1 protein that has not been previously described. The possible mechanisms involved in the modification of the clinical phenotype from an state of hyperinsulinemic hypoglicaemia to a state of hypoinsulinemia and diabetes are discussed (AU)

Encefalopatías prenatales. Nuestra experiencia diagnóstica de 19 años. ¿Hasta dónde con los estudios bioquímicos y genéticos? / Prenatal encephalopathies of unknown origin. Our 19-years experience. To what extent must genetic and biochemical studies be carried out?

Introducción: Consideramos encefalopatías prenatales las que tienen datos clínicos o prenatales de encefalopatía antes del nacimiento. Afectan a un número importante de niños controlados en las consultas de neuropediatría. Pueden ser disruptivas (por problemas vasculares durante el embarazo, drogas, tóxicos o infecciones congénitas), y genéticamente determinadas. Incluimos casos de trastorno del espectro autista y retardo mental sin historia de sufrimiento perinatal o postnatal. Material y métodos: Se revisa nuestra experiencia en el diagnóstico etiológico de las encefalopatías prenatales durante los últimos 19 años. Se analizan los estudios realizados en los casos sin diagnóstico etiológico. Resultados: En el periodo de estudio de 19 años y 5 meses, en la base de datos de neuropediatría figuran 11.910 niños. Tienen establecido el diagnóstico de encefalopatía prenatal 1596 (13,5%). De ellos no tienen diagnóstico etiológico preciso 1.307 niños (81,4%) pese a habérseles realizado múltiples estudios complementarios, fundamentalmente bioquímicos, genéticos y de neuroimagen. Discusión: Muchos de los niños incluidos en este estudio presentan enfermedades raras, estén o no identificadas, que demandan crecientemente un diagnóstico precoz. Enfermedades peroxisomales, lisosomales, mitocondriales, defectos congénitos de la glucosilación, entre otras enfermedades metabólicas hereditarias, infecciones congénitas, cromosomopatías y genopatías, pueden ser indistinguibles clínicamente y necesitan estudios específicos para su identificación. Un diagnóstico precoz precisa estrategias de estudios sistemáticos de forma escalonada, priorizando las enfermedades que tienen posibilidades terapéuticas y en muchos casos es necesaria también una aproximación individualizada. Creemos que las ventajas potenciales del diagnóstico precoz, incluido el ahorro de más pruebas, y la prevención, probablemente sobrepasan el gasto financiero (AU)

Introduction: We examine those prenatal encephalopathies with clinical or neuroimaging data of encephalopathy before the birth. They affect a significant number of children seen by paediatric neurologists. They can be of disruptive origin (due to vascular problems, drugs, toxins or congenital infections), and genetically determined. We include cases of autism spectrum disorder and mental retardation with no history of perinatal of postnatal damages. Material and methods: We analysed our 19 year neuro-paediatric data base in search of prenatal encephalopathies and their diagnostic origin. We also analyse the studies made in the cases with a diagnosis of unknown origin. Results: The 19 year period of study in the data base included 11,910 children, and 1596 (13.5%) were considered as prenatal encephalopathies; 1307 children (81.4%) had a diagnosis of unknown origin, despite many investigations being done in a large number of them. Discussion: Most of the children included in this study suffer a rare disease, and whether they are identified or not, they increasingly require an early diagnosis. Peroxisomal, mitochondrial, lysosomal diseases, carbohydrate glycosylation deficiency syndrome and other inborn error of metabolism, congenital infections and genetic encephalopathies, can be clinically indistinguishable in early life and require specific studies to identify them. Early diagnosis requires strategies using step-wise systematic studies, giving priority to those diseases that could be treated, and in many cases using an individualised approach. We believe that the potential benefits of early diagnosis, including savings on further studies, genetic counselling and prenatal diagnosis, overcome the financial costs (AU)

Prenatal encephalopathies of unknown origin. Our 19-years experience. To what extent must genetic and biochemical studies be carried out?

INTRODUCTION: We examine those prenatal encephalopathies with clinical or neuroimaging data of encephalopathy before the birth. They affect a significant number of children seen by paediatric neurologists. They can be of disruptive origin (due to vascular problems, drugs, toxins or congenital infections), and genetically determined. We include cases of autism spectrum disorder and mental retardation with no history of perinatal of postnatal damages. MATERIAL AND METHODS: We analysed our 19 year neuro-paediatric data base in search of prenatal encephalopathies and their diagnostic origin. We also analyse the studies made in the cases with a diagnosis of unknown origin. RESULTS: The 19 year period of study in the data base included 11,910 children, and 1596 (13.5%) were considered as prenatal encephalopathies; 1307 children (81.4%) had a diagnosis of unknown origin, despite many investigations being done in a large number of them. DISCUSSION: Most of the children included in this study suffer a rare disease, and whether they are identified or not, they increasingly require an early diagnosis. Peroxisomal, mitochondrial, lysosomal diseases, carbohydrate glycosylation deficiency syndrome and other inborn error of metabolism, congenital infections and genetic encephalopathies, can be clinically indistinguishable in early life and require specific studies to identify them. Early diagnosis requires strategies using step-wise systematic studies, giving priority to those diseases that could be treated, and in many cases using an individualised approach. We believe that the potential benefits of early diagnosis, including savings on further studies, genetic counselling and prenatal diagnosis, overcome the financial costs.

Condrodisplasia punctata rizomélica asociada a hipocalcemia neonatal. Comunicación de un nuevo caso / Rhizomelic chondrodysplasia punctata associated toneonatal hypocalcemia. A report of a new case

La condrodisplasia punctata rizomélica clásica (RCDP) es una enfermedad multisistémica rara, de herencia autosómica recesiva, que se caracteriza por un acortamiento proximal de los miembros, calcificaciones punteadas de las epífisis, cataratas, retraso del desarrollo y mortalidad temprana. Se debe a una disfunción del metabolismo peroxisomal, con un perfil bioquímico característico de cada uno de los diversos defectos de metabolismo peroxisómico (AU)

Classic rhizomelic chondrodysplasia punctata (RCDP) is a rare multisystemic disorder with autosomal recessive inheritance that is characterized by proximal shortening of the limbs, punctuate calcifications of the epiphyses, cataracts, developmental delay and early lethality. It´s due to a peroxisomal disorder and exists a biochemical characteristic of each of the various defects in peroxisome metabolism (AU)

[Epilepsy onset between one month and three months of life: our 11 years experience]. / Epilepsia de inicio entre el mes y los tres meses de vida: nuestra experiencia de 11 años.

INTRODUCTION: The prognosis of epilepsy is basically determined by its aetiology. Early onset of seizures is generally associated with poor progress. MATERIAL AND METHODS: We review our experience in epilepsy with children born after 1 January 1997 and who had their first seizure between 1 and 3 months of age before January 2008. RESULTS: Eighteen cases diagnosed with epilepsy and a first seizure between 1 and 3 months of age were included. One case was within the Dravet syndrome spectrum with the c829 T>G c277G heterozygous mutation of the SCN1A gene. Four were cryptogenic epilepsies and thirteen were asymptomatic: 2 were inborn errors of metabolism (biotinidase deficiency with a response to biotin and Leigh's syndrome); 2 were of infectious origin and the remaining nine prenatal encephalopathy. Nine (50%) currently have a severe psychomotor delay and 2 died. The cryptogenic cases had a relatively poor progress. CONCLUSIONS: Our experience corroborates the poor prognosis associated with early onset, between 1 and 3 months, of epileptic seizures. Given the wide aetiological range and the poor prognosis in the absence of specific treatment, an appropriate diagnostic-therapeutic strategy is required to avoid diagnostic uncertainties and can identify potentially treatable cases, such as some inborn errors of metabolism. In this age group, the protocol for convulsions of unknown cause must be the same as that for neonatal convulsions, including treatment with a vitamin cocktail, after collecting biological samples.

Epilepsia de inicio entre el mes y los tres meses de vida: nuestra experiencia de 11 años / Epilepsy onset between one month and three months of life: our 11 years experience

Introducción: El pronóstico de la epilepsia está determinado fundamentalmente por la etiología; se asocia en general peor evolución con comienzo precoz de las crisis. Material y métodos: Se revisa nuestra experiencia en epilepsia en niños nacidos después del 1-1-1997 y que presentaron la primera crisis antes de enero de 2008 a los 1-3 meses de edad. Resultados: Se incluyen 18 casos con el diagnóstico de epilepsia y primera crisis entre 1 y 3 meses de edad. Un caso corresponde al espectro de síndrome de Dravet con la mutación en heterocigosis c829 T>G c277G del gen SCN1A. Cuatro son epilepsias criptogénicas y 13, sintomáticas: 2 errores congénitos del metabolismo (deficiencia de biotinidasa con respuesta a biotina y síndrome de Leigh), 2 de etiología infecciosa y los 9 restantes, encefalopatías prenatales; 9 (50%) tienen un grave retraso psicomotor en la actualidad y 2 fallecieron. En comparación, los casos criptogénicos tuvieron peor evolución. Conclusiones: Nuestra experiencia corrobora el mal pronóstico asociado al inicio precoz, entre 1 y 3 meses, de las crisis epilépticas. Dado el amplio abanico etiológico y el pronóstico sombrío, en ausencia de tratamiento específico, es obligada una adecuada estrategia diagnóstico-terapéutica que evite incertidumbres diagnósticas e identifique casos potencialmente tratables como algunos errores congénitos del metabolismo. En este grupo de edad el protocolo de convulsiones de causa no aclarada debe ser el mismo que el de las convulsiones neonatales, incluido el tratamiento con cóctel vitamínico, tras la recogida de muestras biológicas (AU)

Introduction: The prognosis of epilepsy is basically determined by its aetiology. Early onset of seizures is generally associated with poor progress.Material and methods: We review our experience in epilepsy with children born after 1 January 1997 and who had their first seizure between 1 and 3 months of age before January 2008.Results: Eighteen cases diagnosed with epilepsy and a first seizure between 1 and 3 months of age were included. One case was within the Dravet syndrome spectrum with the c829 T>G c277G heterozygous mutation of the SCN1A gene. Four were cryptogenic epilepsies and thirteen were asymptomatic: 2 were inborn errors of metabolism (biotinidase deficiency with a response to biotin and Leigh’s syndrome); 2 were of infectious origin and the remaining nine prenatal encephalopathy. Nine (50%) currently have a severe psychomotor delay and 2 died. The cryptogenic cases had a relatively poor progress.Conclusions: Our experience corroborates the poor prognosis associated with early onset, between 1 and 3 months, of epileptic seizures. Given the wide aetiological range and the poor prognosis in the absence of specific treatment, an appropriate diagnostic-therapeutic strategy is required to avoid diagnostic uncertainties and can identify potentially treatable cases, such as some inborn errors of metabolism. In this age group, the protocol for convulsions of unknown cause must be the same as that for neonatal convulsions, including treatment with a vitamin cocktail, after collecting biological samples (AU)

Homocistinuria: ¿una gran desconocida? Claves para el diagnóstico en atención primaria / Homocystinurias, a great stranger? Keys for the primary care diagnosis

Las homocistinurias abarcan un grupo de errores congénitos del metabolismo de los aminoácidos azufrados que, con una gran heterogeneidad etiológica y clínica, poseen sin embargo una serie de características comunes que justifican la revisión conjunta de su diagnóstico y tratamiento 1-6. Todos están regidos por una herencia de carácter autosómico recesivo. Habitualmente, se inician durante la infancia, pero pueden hacerlo en cualquier edad de la vida. Sus mecanismos fisiopatológicos, aunque todavía no bien comprendidos por completo, tienen algunos componentes comunes. Las manifestaciones clínicas son de carácter progresivo y cursan, fundamentalmente, con afectación neurológica, oftalmológica, vascular y esquelética. Dos aspectos de esta patología merecen ser especialmente destacados. Por un lado, es una problemática seguramente mucho más frecuente de lo que se pensaba hasta ahora, debido a que la gran variabilidad en el momento de inicio, así como en la gravedad de los signos y síntomas que los pacientes afectados presentan, hace que las formas pauci sintomáticas, o de inicio tardío, pasen desapercibidas o se diagnostiquen en fases muy avanzadas de la enfermedad. Por otro lado, se trata de una patología para la que se dispone actualmente de posibilidades terapéuticas muy efectivas, siempre y cuando se apliquen deforma precoz, antes de que se hayan producido lesiones orgánicas irreversibles. Es importante que los médicos que atienden a los pacientes con manifestaciones clínicas sospechosas de la enfermedad posean los conocimientos y aptitudes necesarios para iniciar el proceso de diagnóstico y tratamiento de los pacientes (AU)

The homocystinurias comprise a congenital error of the sulphur-containing amino acids metabolism, that with a great etiological and clinical heterogeneity, they possess a series of common features that justify the whole revision of their diagnosis and treatment. All of them are governed by an autonomic in heritance recessive nature, autosomal recessive diseases. Usually, the disease is diagnosed during the childhood, but they can appear at any age. Although not still well-understood, their pathogenically mechanisms have some common features. The clinical manifestations are of progressive nature and mainly with neurological, ophthalmologic, vascular and skeletal involvement. It is worth emphasizing two aspects of this pathology. On one hand, it is a probably a more frequent problematic than what has been thought up to date, given that the great variability at onset and the seriousness of the signs and symptoms that the patients might show, make that the pauci symptomatic forms or late onset pass unnoticed or are diagnosed in advanced phases of the disease. On the other hand, it has to do with a pathology for which there are very efficacious therapeutic possibilities at present as long as it is applied early, before irreversible organic lesions have occurred. It is important that doctors who see patients with suspected clinical manifestations of the disease have the necessary knowledge and skills to start the diagnosis process and treatment of the patients (AU)

Avances en el conocimiento de la mucopolisacaridosis tipo II (síndrome de Hunter). Introducción / Advances in our knowledge of mucopolysaccharidosis type II (Hunter syndrome). An introduction

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Eficacia y objetivos terapéuticos del tratamiento enzimático sustitutivo en la mucopolisacaridosis tipo II (síndrome de Hunter) / Effectiveness and therapeutic aims of enzyme replacement therapy in mucopolysaccharidosis type II (Hunter Syndrome)

Introducción. La mucopolisacaridosis tipo II (MPS II), o síndrome de Hunter, es una enfermedad lisosomal de herencia recesiva ligada al cromosoma X, causada por el déficit de la enzima iduronato 2 sulfatasa. El tratamiento de las enfermedades lisosomales en general, y de las MPS en particular, ha cambiado en los últimos 25 años de forma espectacular. En la actualidad, el desarrollo del tratamiento enzimático sustitutivo (TES) ha emergido en las enfermedades lisosomales como una nueva opción terapéutica. Desarrollo. El desarrollo del TES ha ofrecido a estos pacientes los primeros beneficios terapéuticos. En el año 2006, la Food and Drug Administration estadounidense aprobó el uso de la idursulfasa, y en Europa fue la European Medicines Agency quien lo aprobó en enero de 2007. En torno al tratamiento con la idursulfasa se plantea en la actualidad una reflexión: ¿tratar o no tratar el síndrome de Hunter? El TES, a pesar de ser una alternativa prometedora, tiene hoy por hoy algunas limitaciones que hacen imprescindible este planteamiento. A lo largo de esta revisión se analizan tanto los efectos beneficiosos como las limitaciones actuales con el TES. Conclusión. Para responder adecuadamente a esta cuestión, es necesaria la consecución de los siguientes objetivos teóricos: valorar la eficacia terapéutica y la relevancia clínica del TES en la MPS II, desarrollar los biomarcadores adecuados para la monitorización del tratamiento y marcar unos objetivos terapéuticos adecuados que nos ayuden a establecer las indicaciones del TES (AU)

Introduction. Mucopolysaccharidosis type II (MPS II), or Hunter syndrome, is a lysosomal disease that is transmitted by recessive inheritance linked to the X chromosome and is caused by an iduronate-2-sulphatase enzyme deficit. The treatment of lysosomal diseases in general and MPS in particular has undergone spectacular changes over the last 25 years. At present, the development of enzyme replacement therapy (ERT) is being used as a new therapeutic option in the treatment of lysosomal diseases. Development. The development of ERT has offered these patients the first therapeutic benefits. In 2006, the US Food and Drug Administration authorised the use of idursulfase, and in Europe it was approved by the European Medicines Agency in January 2007. The following question arises with respect to treatment with idursulfase today: do we treat Hunter syndrome or not? Despite being a promising alternative, at the present time ERT has a number of limitations that make it necessary to pose this question. Throughout this review we will analyse both the beneficial effects and the current drawbacks of ERT. Conclusions. To be able to answer this question properly, the following theoretical objectives have to be accomplished: appraisal of the therapeutic effectiveness and clinical relevance of ERT in MPS II, development of suitable biomarkers for monitoring the treatment and setting suitable therapeutic aims that help us to establish the indications of ERT (AU)

[Neuropaediatrics and primary care. Our experience in the 21st century]. / Neuropediatría y atención primaria.Nuestra experiencia en el siglo XXI.

INTRODUCTION: The quality of the health care in a major part of neuropaediatrics benefits from appropriate communication and strategies that have been agreed with primary care (PC) paediatricians. PATIENTS AND METHODS: We analyse the children who were assessed in the Neuropaediatric service at the Hospital Universitario Miguel Servet in Saragossa over a period of eight years and we also discuss the most important courses of action followed in the most prevalent problems. RESULTS: Eight reasons for visiting accounted for 86% of the total number: paroxysmal disorders (33%), headache (27%), psychomotor retardation (11.5%), alterations affecting the shape or size of the head (5.6%), problems at school and/or attention deficit (4.5%), behavioural disorders (4.25%), gait disorders (3.5%) and perinatal distress (3.4%). The most frequent diagnoses are headaches/migraines (26%), non-epileptic paroxysmal disorders (16.5%), prenatal encephalopathy (10.5%), epilepsy (8%), mental retardation (7.5%), infantile cerebral palsy (4.6%), cryptogenic attention deficit hyperactivity disorder (ADHD) (3.8%) and cryptogenic autism (3.6%). CONCLUSIONS: The PC paediatrician working in close relation with the children and their families in all cases is the person mainly responsible for conducting a follow-up on some of the most prevalent problems, such as headaches, many non-epileptic paroxysmal disorders and ADHD. The processes must be established, clearly specified, based on the best evidence, with the participation and within reach of all the professionals involved, in order to favour homogeneity and keep variability in the interventions to a minimum. Channels of communication, including the information and communications technologies, need to be set up to allow health professionals to be permanently up-to-date and capable of controlling their patients in the best possible way.

Neuropediatría y atención primaria. Nuestra experiencia en el siglo XXI / Neuropaediatrix and primary care our experience in the 21ST century

Introducción. La calidad asistencial de gran parte de la neuropediatría se beneficia de una adecuada comunicacióny de estrategias consensuadas con los pediatras de atención primaria (AP). Pacientes y métodos. Se analizan los niños valorados en la consulta de neuropediatría del Hospital Universitario Miguel Servet de Zaragoza en ocho años y se exponen las líneas más importantes de actuación en los problemas más prevalentes. Resultados. El 86% de las primeras visitas se reparteentre ocho motivos de consulta: trastornos paroxísticos (33%), cefalea (27%), retraso psicomotor (11,5%), alteraciones de la forma o tamaño de la cabeza (5,6%), problemas escolares y/o atención deficiente (4,5%), alteraciones del comportamiento (4,25%), trastornos de la marcha (3,5%) y sufrimiento perinatal (3,4%). Los diagnósticos más frecuentes son cefaleas/migrañas(26%), trastornos paroxísticos no epilépticos (16,5%), encefalopatía prenatal (10,5%), epilepsia (8%), retardo mental (7,5%), parálisis cerebral infantil (4,6%), trastorno por déficit de atención con hiperactividad (TDAH) criptogénico (3,8%) y autismo criptogénico (3,6%). Conclusiones. El pediatra de AP cercano a los niños y sus familias en todos los casos es el principalresponsable del seguimiento de algunos de los problemas más prevalentes, como cefaleas, muchos trastornos paroxísticos no epilépticos y TDAH. Los procesos deben estar establecidos, claramente explicitados, basados en las mejores evidencias, con la participación y al alcance de todos los profesionales involucrados, en beneficio de la homogeneidad y reducida variabilidadde las actuaciones. Es necesario establecer vías de comunicación, incluidas las tecnologías de la información y comunicación para una continua actualización y el mejor control de los pacientes

Introduction. The quality of the health care in a major part of neuropaediatrics benefits from appropriatecommunication and strategies that have been agreed with primary care (PC) paediatricians. Patients and methods.We analyse the children who were assessed in the Neuropaediatric service at the Hospital Universitario Miguel Servet in Saragossa over aperiod of eight years and we also discuss the most important courses of action followed in the most prevalent problems. Results. Eight reasons for visiting accounted for 86% of the total number: paroxysmal disorders (33%), headache (27%), psychomotor retardation (11.5%), alterations affecting the shape or size of the head (5.6%), problems at school and/or attention deficit (4.5%), behavioural disorders (4.25%), gait disorders (3.5%) and perinatal distress (3.4%). The most frequent diagnoses areheadaches/migraines (26%), non-epileptic paroxysmal disorders (16.5%), prenatal encephalopathy (10.5%), epilepsy (8%), mental retardation (7.5%), infantile cerebral palsy (4.6%), cryptogenic attention deficit hyperactivity disorder (ADHD) (3.8%) and cryptogenic autism (3.6%). Conclusions. The PC paediatrician working in close relation with the children and theirfamilies in all cases is the person mainly responsible for conducting a follow-up on some of the most prevalent problems, such as headaches, many non-epileptic paroxysmal disorders and ADHD. The processes must be established, clearly specified, based on the best evidence, with the participation and within reach of all the professionals involved, in order to favourhomogeneity and keep variability in the interventions to a minimum. Channels of communication, including the information and communications technologies, need to be set up to allow health professionals to be permanently up-to-date and capable of controlling their patients in the best possible way

[Hereditary juvenile cobalamin deficiency due to mutations in GIF gene]. / Déficit de cobalamina hereditario juvenil causado por mutaciones en el gen GIF.

Inborn errors of cobalamin (Cbl) metabolism affect its absorption, transport, as well as its intracellular metabolism. Hereditary juvenile megaloblastic anaemia due to cobalamin deficiency, results from defects in Cbl absorption. There is a lack of vitamin B12 in congenital pernicious anaemia due to intrinsic factor deficiency and megaloblastic anaemia 1 due to selective intestinal malabsorption of vitamin B12 or Imerslund-Gräsbeck syndrome. Differential diagnosis can't be accomplished only by clinical and biochemical findings. We present a patient from Spain with a megaloblastic anaemia due to intrinsic factor deficiency (IFD). The patient is a compound heterozygous in GIF gene for a splice site mutation inherited from his mother and a missense change inherited from his father. The identification of disease-causing mutations in specific genes has improved our ability to diagnose many of these conditions.

[Our experience in the diagnosis of peroxisomal diseases with an abnormal fatty acid profile]. / Nuestra experiencia diagnóstica en enfermedades peroxisomales con alteración del perfil de ácidos grasos

INTRODUCTION: The aetiology and clinical features of peroxisomal diseases vary widely. An altered very-long-chain fatty acid (VLCFA) profile is commonly found in many of these diseases, and this makes it easier to point the diagnosis in the right direction. PATIENTS AND METHODS: We review our experience in the diagnosis of cases of peroxisomal diseases with an altered VLCFA pattern; these were determined in serum only when there was a strong clinical suspicion up to the end of 1998, when their quantification by chromatography was introduced into our laboratory. RESULTS: The neuropaediatric database included 10,239 cases between May 1990 and 1st October 2007. Ten cases of peroxisomal disease with an altered VLCFA pattern were identified, all of them males. There were two cases of Zellweger syndrome spectrum, one unclassified peroxisomal oxidation defect and seven X-linked adrenoleukodystrophies (four with neurological compromise and three with no neurological damage; two were identified in siblings of patients and the other due to the presence of Addison's syndrome). CONCLUSIONS: In our 10 cases, the diagnosis was guided by the clinical or familial features that led to the determination of VLCFA. Being able to determine VLCFA makes early systematic diagnosis of patients possible. At present, VLCFA determination is performed when there is a clinical suspicion of Zellweger spectrum, suspected X-linked adrenoleukodystrophy/adrenomyeloneuropathy of unclear causation, Addison's disease, both in males and females, and above all in cases of chronic encephalopathy of unknown causation, with or without prenatal onset.

Déficit de cobalamina hereditario juvenil causado por mutaciones en el gen GIF / Hereditary juvenile cobalamin deficiency due to mutations in GIFgene

Los errores congénitos del metabolismo de la cobalamina afectan a su absorción, transporte o metabolismo intracelular. La anemia megaloblástica hereditaria juvenil por déficit de vitamina B12 está causada por una malabsorción de cobalamina. En la anemia perniciosa congénita por déficit de factor intrínseco, y en la anemia megaloblástica 1 por malabsorción de vitamina B12, causada por un defecto en el receptor vitamina B12/factor intrínseco o síndrome de Imerslund-Gräsbeck, existe un déficit de vitamina B12. El diagnóstico diferencial entre estas dos entidades no puede ser completado únicamente mediante la clínica y los datos de laboratorio. Presentamos un paciente español con anemia megaloblástica hereditaria juvenil por déficit de factor intrínseco, heterocigoto compuesto para dos mutaciones distintas en el gen GIF. La identificación de mutaciones causantes de la enfermedad en genes específicos ha mejorado nuestra capacidad de diagnóstico y tratamiento de estas situaciones (AU)

Inborn errors of cobalamin (Cbl) metabolism affect its absorption, transport, as well as its intracellular metabolism. Hereditary juvenile megaloblastic anaemia due to cobalamin deficiency, results from defects in Cbl absorption. There is a lack of vitamin B12 in congenital pernicious anaemia due to intrinsic factor deficiency and megaloblastic anaemia 1 due to selective intestinal malabsorption of vitamin B12 or Imerslund-Gräsbeck syndrome. Differential diagnosis can't be accomplished only by clinical and biochemical findings. We present a patient from Spain with a megaloblastic anaemia due to intrinsic factor deficiency (IFD). The patient is a compound heterozygous in GIF gene for a splice site mutation inherited from his mother and a missense change inherited from his father. The identification of disease-causing mutations in specific genes has improved our ability to diagnose many of these conditions (AU)

Nuestra experiencia diagnóstica en enfermedades peroxisomales con alteración del perfil de ácidos grasos / Our experience in the diagnosis of peroxisomal diseases with an abnormal fatty acid profile

Introducción. Las enfermedades peroxisomales tienen una gran heterogeneidad etiológica y clínica. Un perfil alterado de ácidos grasos de cadena muy larga (AGCML) es común a muchas de ellas, lo que facilita su orientación diagnóstica.Pacientes y métodos. Se revisa nuestra experiencia diagnóstica en los casos de enfermedad peroxisomal con patrón alterado de AGCML, que se determinaban en suero sólo ante fuerte sospecha clínica hasta finales de 1998, fecha en que se introdujo en nuestro laboratorio su cuantificación por cromatografía. Resultados. En la base de datos de neuropediatría de mayo de 1990 a 1 de octubre de 2007 figuran 10.239 casos. Se han identificado 10 casos de enfermedad peroxisomal con patrón alterado de AGCML, todos varones: dos casos de espectro de síndrome de Zellweger, un defecto de la beta-oxidación peroxisomal sin tipificar y siete adrenoleucodistrofias ligadas a X (cuatro con afectación neurológica y tres sin daño neurológico; dosidentificados por ser hermanos de enfermos y el otro por presentar un síndrome de Addison). Conclusiones. En nuestros 10 casos, el diagnóstico se orientó por el cuadro clínico o familiar que llevó a la determinación de AGCML. La disponibilidad de la determinación de AGCML permite el diagnóstico siste-mático de pacientes de forma precoz. Actualmente, la realizamos ante sospecha clínica del espectro Zellweger, sospecha de adrenoleucodistrofia/adrenomieloneuropatía ligada a X, leucoencefalopatías de causa no aclarada, enfermedad de Addison, tanto en varones como mujeres, y ante toda encefalopatía crónica de causa no aclarada de inicio prenatal o no

Introduction. The aetiology and clinical features of peroxisomal diseases vary widely. An altered very-long-chain fatty acid (VLCFA) profile is commonly found in many of these diseases, and this makes it easier to point the diagnosis in the right direction. Patients and methods. We review our experience in the diagnosis of cases of peroxisomal diseases with analtered VLCFA pattern; these were determined in serum only when there was a strong clinical suspicion up to the end of 1998, when their quantification by chromatography was introduced into our laboratory. Results. The neuropaediatric database included 10,239 cases between May 1990 and 1st October 2007. Ten cases of peroxisomal disease with an altered VLCFApattern were identified, all of them males. There were two cases of Zellweger syndrome spectrum, one unclassified peroxisomal oxidation defect and seven X-linked adrenoleukodystrophies (four with neurological compromise and three with no neurological damage; two were identified in siblings of patients and the other due to the presence of Addison’s syndrome).Conclusions. In our 10 cases, the diagnosis was guided by the clinical or familial features that led to the determination of VLCFA. Being able to determine VLCFA makes early systematic diagnosis of patients possible. At present, VLCFA determination is performed when there is a clinical suspicion of Zellweger spectrum, suspected X-linked adrenoleuko - dystrophy/adrenomyeloneuropathy of unclear causation, Addison’s disease, both in males and females, and above all in cases of chronic encephalopathy of unknown causation, with or without prenatal onset

[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)