[Neonatal viral meningitis. The importance of the polymerase chain reaction in their diagnosis]. / Meningitis viricas neonatales. Importancia de la reaccion en cadena de la polimerasa en su diagnostico.

INTRODUCTION: The different types of viral meningitis constitute a condition that is relatively frequent in newborn infants, although in many cases they are underdiagnosed due to the absence of pleocytosis in the cerebrospinal fluid (CSF). AIMS: To describe the clinical features and laboratory findings of newborn infants with viral meningitis and to highlight the importance of the polymerase chain reaction (PCR) in the CSF to diagnose this condition. PATIENTS AND METHODS: A retrospective review of the medical records of newborn infants hospitalised in the neonatology section who had been diagnosed with viral meningitis between May 2014 and May 2017. RESULTS: Altogether 17 cases of viral meningitis were registered (15 caused by enterovirus and two due to parechovirus), which accounts for 14.8% of all newborns hospitalised owing to febrile symptoms. All of them had fever (100%), and other notable symptoms were irritability (76%) and rejection of feeding (65%). Normal cellularity was found in the CSF without high protein levels in 88% of them, and without hypoglycorrhachia in all of them (100%), which meant that many of these children had previously been left with a diagnosis of a febrile syndrome with no focus. These data stress the need to perform the PCR in the CSF of newborn infants who have a fever without a focus, due to the normal status of the results of the complementary tests in most cases. Subsequent neurological follow-up was performed in 64.7% of the children in the neurology service, without any neurological sequelae being found, except in one case. CONCLUSIONS: Multiple PCR in the CSF has become an essential diagnostic technique in cases of newborn infants with a suspected infection, and replaces viral culture as the reference test due its being quicker and more sensitive.

TITLE: Meningitis viricas neonatales. Importancia de la reaccion en cadena de la polimerasa en su diagnostico.Introduccion. Las meningitis viricas representan una entidad relativamente frecuente en los recien nacidos, aunque en muchos casos infradiagnosticadas, ante la ausencia de pleocitosis en el liquido cefalorraquideo (LCR). Objetivos. Describir las caracteristicas clinicas y los hallazgos de laboratorio de neonatos con meningitis viricas y destacar la importancia de la reaccion en cadena de la polimerasa (PCR) en el LCR para diagnosticar esta patologia. Pacientes y metodos. Revision retrospectiva de historias clinicas de neonatos ingresados en la seccion de neonatologia diagnosticados de meningitis virica entre mayo de 2014 y mayo de 2017. Resultados. Se registraron 17 casos de meningitis virica (15 causadas por enterovirus y dos por parechovirus), que constituyen el 14,8% de los neonatos ingresados por sindrome febril. Todos manifestaron fiebre (100%), y otros sintomas destacados fueron irritabilidad (76%) y rechazo de la ingesta (65%). El 88% curso con celularidad normal en el LCR y sin hiperproteinorraquia, y el 100%, sin hipoglucorraquia, por lo que previamente muchos de estos niños quedaban con el diagnostico de sindrome febril sin foco. Estos datos resaltan la necesidad de realizar la PCR en el LCR a neonatos con fiebre sin foco, debido a la normalidad de las pruebas complementarias en la mayoria de los casos. El 64,7% de los niños recibio seguimiento neurologico posterior en consulta de neurologia, sin objetivarse secuelas neurologicas, salvo en uno de ellos. Conclusiones. La PCR multiple en el LCR se ha convertido en una tecnica diagnostica imprescindible en el recien nacido con sospecha de infeccion y sustituye al cultivo viral como prueba de referencia por su mayor rapidez y sensibilidad.

A new severe mutation in the SLC5A7 gene related to congenital myasthenic syndrome type 20.

Congenital myasthenic syndromes are a group of genetically determined rare diseases resulting from ultrastructural alterations in synaptic proteins. Up to 32 genes are known to be involved in those syndromes and many mutations have been reported, of which less than 8% affect the presynaptic complex. One of these syndromes is caused by the impairment of the presynaptic sodium-dependent high-affinity choline transporter 1, as a result of a mutation of the SCL5A7 gene associated with congenital myasthenic syndrome type 20 (MIM # 617143). We present a new case of this syndrome, caused by a mutation not previously described. A full term infant presented with acute respiratory failure and generalized weakness. The genetic analysis revealed the patient to be compound heterozygous for a new mutation of the SCL5A7 gene. The genetic analysis of congenital myasthenic syndromes provide information on the ultrastructural underlying mechanisms, which is valuable for differential diagnosis and specific treatments.

[Value of electroencephalography in the early detection of neonatal leucinosis]. / Aportacion de la electroencefalografia en la deteccion temprana de leucinosis neonatal.

INTRODUCTION: Leucinosis is a severe neonatal metabolic disease. It is the consequence of the genetically determined enzyme deficiency of the complex formed by decarboxylase-dihydrolipoyl transacylase and dihydrolipoyl dehydrogenase, and of the subsequent accumulation of precursor metabolites, long branched-chain amino acids and their alpha ketoacids. They are powerful neurotoxins, responsible for the swift onset of oedema and diffuse cerebral demyelination. Delays in its diagnosis usually result in severe psychomotor sequelae or even death. CASE REPORT: We report the case of a newborn female patient with severe neonatal encephalopathy, epileptic seizures and an electroencephalogram (EEG) with certain special characteristics that guided the diagnosis towards that of possible leucinosis. Early diagnosis makes it possible to establish specific treatment and achieve a favourable patient outcome. CONCLUSIONS: An EEG in patients with suspected neonatal encephalopathy offers highly cost-effective functional information at a low cost, especially because it promotes early diagnoses and treatments. In cases of leucinosis, EEG presents peculiar signs that are easily recognisable in early periods in most patients, as occurred in the case reported here. We believe EEG should be included in screening for neonatal encephalopathies because it is a valuable, innocuous and generally accessible diagnostic technique. It is especially helpful in treatable metabolic diseases, such as leucinosis.

TITLE: Aportacion de la electroencefalografia en la deteccion temprana de leucinosis neonatal.Introduccion. La leucinosis es una metabolopatia neonatal grave. Es consecuencia del deficit enzimatico determinado geneticamente del complejo descarboxilasa-dihidrolipoil transacilasa y dihidrolipoil deshidrogenasa, y del acumulo consecuente de los metabolitos precursores, aminoacidos ramificados de cadena larga y sus alfa-cetoacidos. Son potentes neurotoxicos, responsables del rapido establecimiento de edema y desmielinizacion cerebral difusa. La demora en el diagnostico suele provocar graves secuelas psicomotoras o incluso la muerte. Caso clinico. Se presenta una paciente neonata con encefalopatia neonatal grave, crisis epilepticas y un electroencefalograma (EEG) con unas caracteristicas especiales que oriento el diagnostico hacia una posible leucinosis. El diagnostico temprano permitio instaurar rapidamente el tratamiento especifico y conseguir una evolucion favorable de la paciente. Conclusiones. El EEG en pacientes con sospecha de encefalopatia neonatal ofrece informacion funcional de alta rentabilidad con un bajo coste, en especial por promover diagnosticos y tratamientos tempranos. El EEG en la leucinosis presenta signos peculiares, reconocibles en periodos tempranos en la mayor parte de los afectados, como ocurrio en el caso descrito. Parece recomendable integrar el EEG en el cribado de encefalopatias neonatales por ser una tecnica diagnostica valiosa, inocua y, por lo general, accesible y especialmente de ayuda en metabolopatias tratables, como la leucinosis.

Midriasis congénita como signo inicial de displasia septo-óptica / Congenital mydriasis as an initial sign of septo-optic dysplasia

La displasia septo-óptica (DSO)[MIM182230] es una entidad heterogénea poco frecuente, caracterizada por la tríada clásica: hipoplasia del nervio óptico, anomalías de las hormonas hipofisarias y defectos de la línea media cerebral (incluyendo agenesia del septumpellucidumy/o del cuerpo calloso; también se han descrito malformaciones corticales asociadas, citado como síndrome DSO plus). Referimos el primer caso clínico conocido, en el que el signo de diagnóstico inicial de DSO fue una midriasis bilateral, como manifestación de hipoplasia de ambos nervios ópticos, hipoplasia hipofisaria y disgenesia cerebral con alteración de migración neuronal. Discutimos el diagnóstico diferencial de la midriasis congénita (AU)

Septo-optic dysplasia (SOD)[MIM182230] consisting of a heterogeneous and uncommon condition characterised by the classic triad: optic nerve hypoplasia, abnormalities of pituitary hormone, and defects of the brain midline (including agenesis of the septum pellucidum and/or the corpus callosum; it has also been described associated cortical malformations, it was referred to as SOD plus syndrome).We report the first known case in which the initial diagnostic sign of SOD was a bilateral mydriasis as a manifestation of hypoplasia of both optic nerves, pituitary hypoplasia andcerebral dysgenesis with neuronal migration disorder. We discuss the differential diagnosis of congenital mydriasis (AU)

[Congenital mydriasis as an initial sign of septo-optic dysplasia]. / Midriasis congénita como signo inicial de displasia septo-óptica.

Septo-optic dysplasia (SOD)[MIM182230] consisting of a heterogeneous and uncommon condition characterised by the classictriad: optic nerve hypoplasia, abnormalities of pituitary hormone, and defects of thebrain midline (including agenesis of the septum pellucidum and/or the corpus callosum; ithas also been described associated cortical malformations, it was referred to as SOD plus syndrome).We report the first known case in which the initial diagnostic sign of SOD was a bilateralmydriasis as a manifestation ofhypoplasia of both optic nerves, pituitary hypoplasia andcerebral dysgenesis with neuronal migration disorder.We discuss thedifferential diagnosis of congenital mydriasis.

Ictiosis ligada al cromosoma X asociada a epilepsia, hiperactividad, autismo y retraso mental, por microdeleción Xp22.31 / X-chromosome-linked ichthyosis associated to epilepsy, hyperactivity, autism and mental retardation, due to the Xp22.31 microdeletion

La ictiosis ligada al cromosoma X está causada por mutación o deleción del gen STS asociado a la deficiencia dela enzima sulfatasa esteroidea, localizada en la parte distal del brazo corto del cromosoma X (Xp22.3-pter), cerca de la región pseudoautosómica. Dependiendo de su extensión, puede presentarse como una entidad aislada o en combinación con un síndrome de genes contiguos, asociándose a otras enfermedades monogénicas, así como a otros trastornos mentales.Se revisa la bibliografía, destacando la importancia de la región Xp22.3-pter y la mayor incidencia de trastornos neurológicos en varones (trastorno por déficit de atención/hiperactividad, autismo y retraso mental ligado a X). Se discuteel papel e implicación de estos genes en la enfermedad y se propone la posible contribución del gen PNPLA4, originalmente descrito como GS2 y codificante de la fosfolipasa A2 independiente del calcio-eta, involucrada en el metabolismolipoproteico, como una de las causas de autismo. Se ha objetivado mejoría tras el tratamiento con citicolina, a través del papel que este nootropo desempeña en la biosíntesis de fosfolípidos estructurales involucrados en la formación y reparación de la membrana neuronal (AU)

X-chromosome-linked ichthyosis is caused by mutation or deletion of the STS gene associated with a deficiency of the enzyme steroid sulphatase, located in the distal part of the short arm of the X chromosome (Xp22.3-pter), close tothe pseudo-autosomal region. Depending on its size, it can present as an isolated entity or combined with a syndrome caused by neighbouring genes, thus associating itself with other monogenic diseases as well as other mental disorders.The most relevant findings from the literature review are the importance of the Xp22.3-pter region and the higher incidence of neurological disorders among males (attention deficit hyperactivity disorder, autism and X-linked mental retardation). The role and implication of these genes in the disease are discussed and the authors suggest a possiblecontribution of the gene PNPLA4, which was originally described as GS2 and codes for calcium-independent phospholipase A2 beta, involved in lipoprotein metabolism, as one of the causes of autism. Improvements have been observed followingtreatment with citicoline, thanks to the role this nootropic plays in the biosynthesis of structural phospholipids involved inthe formation and repair of the neuronal membrane (AU)

[Hemophagocytic syndrome secondary to visceral leishmaniasis]. / Síndrome hemofagocítico secundario a leishmaniasis visceral.

Haemophagocytic syndrome is a disease diagnosed according to clinical and analytical criteria, related to many infectious diseases. It is exceptionally described in patients infected with Leishmania. Visceral leishmaniasis is an uncommon disease in our country except in some areas where it is endemic. Its diagnosis is sometimes difficult and the use of other methods currently available is needed. Haemophagocytic syndrome treatment is based on established chemotherapy protocols, but when it is secondary to Visceral Leishmaniasis, it may be an exception, since the abnormalities can be resolved by treatment of the infection itself. This treatment has improved recently as Liposomal Amphotericin B has replaced classic antimonials, being more beneficial due to less adverse effects and a shorter treatment time.

Síndrome hemofagocítico secundario a leishmaniasis visceral / Hemophagocytic syndrome secondary to visceral leishmaniasis

El síndrome hemofagocítico es una enfermedad diagnosticada basándose en criterios clínicos y analíticos, relacionada con numerosas entidades infecciosas. De forma excepcional se ha descrito en pacientes infectados con el parásito Leishmania. La leishmaniasis visceral es una patología infrecuente en nuestro país, salvo en zonas concretas donde es endémica. Su diagnóstico en ocasiones es difícil y hay que recurrir a varios de los métodos actualmente disponibles. El tratamiento del síndrome hemofagocítico se fundamenta en pautas quimioterápicas protocolizadas, aunque puede representar una excepción cuando es secundario a la leishmaniasis visceral, ya que el tratamiento antiinfeccioso suele resolver las alteraciones por sí mismo. Dicha terapia ha evolucionado en los últimos tiempos al sustituir la anfotericina B liposomal a las pautas clásicas con antimoniales y logrando beneficios por sus menores efectos secundarios y por acortar el tiempo de tratamiento (AU)

Haemophagocytic syndrome is a disease diagnosed according to clinical and analytical criteria, related to many infectious diseases. It is exceptionally described in patients infected with Leishmania. Visceral leishmaniasis is an uncommon disease in our country except in some areas where it is endemic. Its diagnosis is sometimes difficult and the use of other methods currently available is needed. Haemophagocytic syndrome treatment is based on established chemotherapy protocols, but when it is secondary to Visceral Leishmaniasis, it may be an exception, since the abnormalities can be resolved by treatment of the infection itself. This treatment has improved recently as Liposomal Amphotericin B has replaced classic antimonials, being more beneficial due to less adverse effects and a shorter treatment time (AU)

Enfermedades peroxisomales: análisis de los niveles de ferritina en el síndrome cerebrohepatorrenal de Zellweger / Peroxisomal diseases: an analysis of ferritin levels in Zellweger’s cerebrohepatorenal syndrome

No disponible

[Partial duplication of chromosome 4q (q31, q35): Auriculo-acro-renal syndrome]. / Duplicación parcial del cromosoma 4q (q31, q35): síndrome aurículo-acro-renal.

The partial trisomy 4q is a strange chromosomal illness. This illness is caused by the duplication of a portion of chromosome 4. In most of the cases, it is the result of a balanced translocation in one of the progenitors. The "de novo" appearance is less common. We present a patient with a partial "de novo" duplication in the distal segment of the long arm of chromosome 4 (q31, q35), in association with Robertsonian translocation between chromosomes 14 and 21. This association has not been described previously. In the 4q duplication, the relationship between the phenotype and the parts of the duplicated segment is not well defined, although it seems clear that the renal anomalies and/or thumbs abnormalities are a characteristic manifestation. We have reviewed the literature and, of the cases previously described with trisomy q31-35, we came to the conclusion that this region of chromosome 4 may also be involved in constituting the "Syndrome of partial trisomy 4q" or Auriculo-acro-renal Syndrome".

Duplicación parcial del cromosoma 4q (q31, q35): síndrome aurículo-acro-renal / Partial duplication of chromosome 4q (q31, q35): auriculo-acro-renal syndrome

La trisomía parcial 4q es una enfermedad cromosómica rara, causada por una duplicación de una porción del cromosoma 4. En la mayoría de los casos resulta de una translocación balanceada de uno de los progenitores; siendo menos frecuente la aparición de novo. Presentamos un paciente con una duplicación parcial de novo del segmento distal del brazo largo del cromosoma 4 (q31, q35) asociada a translocación robertsoniana entre los cromosomas 14 y 21; asociación previamente no descrita. En la duplicación 4q no queda bien definida la relación entre el fenotipo y las partes del segmento duplicadas, aunque parece claro que anomalías renales y/o de pulgares son una manifestación característica. Revisamos la literatura médica, y de los casos previamente descritos con trisomía q31-35 concluimos que esta región del cromosoma 4 también estaría comprometida en constituir el "síndrome de la trisomía parcial 4q" o "síndrome aurículo-acro-renal"(AU)

The partial trisomy 4q is a strange chromosomal illness. This illness is caused by the duplication of a portion of chromosome 4. In most of the cases, it is the result of a balanced translocation in one of the progenitors. The "de novo" appearance is less common. We present a patient with a partial "de novo" duplication in the distal segment of the long arm of chromosome 4 (q31, q35), in association with Robertsonian translocation between chromosomes 14 and 21. This association has not been described previously. In the 4q duplication, the relationship between the phenotype and the parts of the duplicated segment is not well defined, although it seems clear that the renal anomalies and/or thumbs abnormalities are a characteristic manifestation. We have reviewed the literature and, of the cases previously described with trisomy q31-35, we came to the conclusion that this region of chromosome 4 may also be involved in constituting the "Syndrome of partial trisomy 4q" or Auriculo-acro-renal Syndrome" (AU)

Síndrome de Walker-Warburg en gemelos de etnia gitana / No disponible

No disponible

[Neurocristopathies: a high incidence of cerebral dysgenesis in patients with Hirschsprung's disease]. / Neurocrestopatías: alta frecuencia de disgenesias cerebrales en pacientes con enfermedad de Hirschsprung.

INTRODUCTION: Hirschsprung's disease (HD), or aganglionic megacolon, is a congenital disorder that is characterised by the absence of ganglion cells in the submucosal and myenteric plexuses of the intestine, which is caused by the failure of these cells to migrate from the neural crest (neurocristopathy). Cerebral dysgenesis and polymalformation syndromes have been reported in association with HD, thus suggesting an abnormal morphogenesis. AIM: To study the frequency of cerebral malformations in patients with HD in our environment. PATIENTS AND METHODS: We conducted a retrospective study of 41,666 live newborn infants, over the period 1993-2003, and 17 cases of HD where identified. RESULTS: The incidence of HD in the health district of the province of Albacete is 1.68 per 5,000 live newborn infants. Of the 17 patients with HD who were studied, 10 were isolated (58.8%) and seven (41.1%) were associated to other structural abnormalities and psychomotor retardation. Three of the cases in this latter group were due to chromosome pathology (trisomy 21, Down syndrome), two were caused by specific polymalformation syndromes (one Mowat-Wilson syndrome and one possible FG syndrome), one was due to a pattern of abnormalities that did not fit any known syndrome, and one had a normal phenotype and isolated cerebral dysgenesis. In all of cases the neuroimaging studies identified cerebral dysgenesis that was compatible with neuronal migration disorders. CONCLUSIONS: The frequency of association of HD, either isolated or within the context of a specific malformation syndrome, with neuronal migration disorders is high (23.5%). We suggest a full genetic and neurological evaluation should be carried out in patients with HD, together with brain imaging studies in order to rule out the possibility of cerebral dysgenesis.

[Pena-Shokeir syndrome type I, associated to Klippel-Feil syndrome type II in the same family]. / Secuencia de Pena-Shokeir tipo I, asociada a síndrome de Klippel-Feil tipo II en la misma familia.

INTRODUCTION: In 1974 Pena and Shokeir described an early lethal disorder (OMIM 208150) that was characterised by neurogenic arthrogryposis, facial abnormalities and pulmonary hypoplasia. It has recently been suggested that it is secondary to the reduction of movements in the uterus due to an intrinsic pathology regardless of the cause (FADS, foetal akinesia deformation sequence). Klippel-Feil (K-F) syndrome (OMIM 118100) is defined by the congenital fusion of one or two cervical vertebrae, and clinically manifests as a shortened neck, with limited head movements, and may also be associated to other malformations. CASE REPORTS: We report the case of a family diagnosed with K-F syndrome type II. It was observed in the father and one daughter; another child presented Pena-Shokeir type I and died during the neonatal period. Both siblings presented anomalies in the central nervous system. CONCLUSIONS: The incidence of FADS syndrome is 1/10,000 deliveries and that of K-F syndrome is between 1/35,000 and 1/42,000 births. We reviewed the literature on FADS syndrome and no familiar association with K-F syndrome was found among its causes. Our aim is to report that an association between the two conditions is possible, which is very important for establishing suitable genetic counselling.

Congenital gingival hyperplasia in a neonate with foetal valproate syndrome.

There are several causes of gingival hyperplasia and one of the most well-known is drug-induced gingival enlargement. Nevertheless, causes of congenital gingival enlargement include only hereditary and metabolic disorders. Only one case of drug-induced congenital gingival hyperplasia has been reported. We present the second neonate with gingival hyperplasia in the context of foetal valproate syndrome and review the literature.

[Embryopathy due to valproic acid with severe malformations in the central nervous system]. / Embriopatía por ácido valproico con malformaciones graves del sistema nervioso central.

INTRODUCTION: Embryogenetic disorders are one of the most serious problems in the life of an epileptic. Over the last few decades many antiepileptic drugs, including valproic acid, have been shown to have teratogenic properties. Embryopathy due to valproate, also known as fetal valproate syndrome, is a well-known and documented example of these conditions. CASE REPORT: We report the case of a preterm newborn infant who, at birth, exhibited a syndrome characterised by facial dysmorphia, gingival hyperplasia, neurological hyperexcitability and multiple malformations, the most striking of which was the presence of predominantly temporal atrophy in the left brain hemisphere. The most significant event in the medical history of the case was the mother's taking valproate in monotherapy throughout the entire period of gestation as treatment for generalised idiopathic epilepsy that was diagnosed during adolescence. Screening precluded the most common metabolic, hereditary or infectious causes that can cause embryopathies. CONCLUSIONS: The mother's history of taking valproic acid and the specific findings that coincided in the peculiar embryopathy of this patient enabled us to link them.

[Vegetarian diet in glutaric aciduria type I]. / Dieta vegetariana en aciduria glutárica tipo I.

Glutaric aciduria type I is an autosomal recessive metabolic disease (1 case/30,000) characterized by a progressive dystonic-diakinetic syndrome in children. Pathologic examination reveals striatal degeneration of the caudate and putamen nucleus and biochemical analysis shows glutaryl CoA dehydrogenase deficiency. Values of glutaric and -hydroxyglutaric acids in urine are usually increased. Currently, the disease is considered untreatable since there are usually irreversible lesions in the central nervous system at diagnosis. However, treatment can be provided to pre-symptomatic children and usually to the siblings of patients with this diagnosis. We present the case of a 23-month-old boy, with macrocephaly and minimal neurologic manifestations at diagnosis, which were attributed to his semivegetarian diet. A dietary regimen and vitamin supplementation halted and even improved symptomatic progression of the disease. We conclude that amino and organic acids in urine should be investigated in all children with progressive macrocephaly of unknown etiology to rule out glutaric aciduria type I.