RESUMEN

Disclaimer: These ACMG Standards and Guidelines are intended as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these standards and guidelines is voluntary and does not necessarily assure a successful medical outcome. These Standards and Guidelines should not be considered inclusive of all proper procedures and tests or exclusive of others that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, clinical laboratory geneticists should apply their professional judgment to the specific circumstances presented by the patient or specimen. Clinical laboratory geneticists are encouraged to document in the patient's record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these Standards and Guidelines. They also are advised to take notice of the date any particular guideline was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.Cerebral creatine deficiency syndromes are neurometabolic conditions characterized by intellectual disability, seizures, speech delay, and behavioral abnormalities. Several laboratory methods are available for preliminary and confirmatory diagnosis of these conditions, including measurement of creatine and related metabolites in biofluids using liquid chromatography-tandem mass spectrometry or gas chromatography-mass spectrometry, enzyme activity assays in cultured cells, and DNA sequence analysis. These guidelines are intended to standardize these procedures to help optimize the diagnosis of creatine deficiency syndromes. While biochemical methods are emphasized, considerations for confirmatory molecular testing are also discussed, along with variables that influence test results and interpretation.Genet Med 19 2, 256-263.

Asunto(s)

Amidinotransferasas/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/genética , Encefalopatías Metabólicas Innatas/genética , Creatina/deficiencia , Creatina/metabolismo , Guanidinoacetato N-Metiltransferasa/deficiencia , Discapacidad Intelectual/genética , Trastornos del Desarrollo del Lenguaje/genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Trastornos del Movimiento/congénito , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/deficiencia , Proteínas Represoras/genética , Trastornos del Habla/genética , Amidinotransferasas/sangre , Amidinotransferasas/líquido cefalorraquídeo , Amidinotransferasas/genética , Amidinotransferasas/orina , Errores Innatos del Metabolismo de los Aminoácidos/sangre , Errores Innatos del Metabolismo de los Aminoácidos/líquido cefalorraquídeo , Errores Innatos del Metabolismo de los Aminoácidos/orina , Encefalopatías Metabólicas Innatas/sangre , Encefalopatías Metabólicas Innatas/líquido cefalorraquídeo , Encefalopatías Metabólicas Innatas/orina , Técnicas de Laboratorio Clínico/métodos , Creatina/sangre , Creatina/líquido cefalorraquídeo , Creatina/genética , Creatina/orina , Discapacidades del Desarrollo/sangre , Discapacidades del Desarrollo/líquido cefalorraquídeo , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/orina , Pruebas Genéticas/normas , Genética Médica/normas , Genómica , Guanidinoacetato N-Metiltransferasa/sangre , Guanidinoacetato N-Metiltransferasa/líquido cefalorraquídeo , Guanidinoacetato N-Metiltransferasa/genética , Guanidinoacetato N-Metiltransferasa/orina , Guías como Asunto , Humanos , Discapacidad Intelectual/sangre , Discapacidad Intelectual/líquido cefalorraquídeo , Discapacidad Intelectual/orina , Trastornos del Desarrollo del Lenguaje/sangre , Trastornos del Desarrollo del Lenguaje/líquido cefalorraquídeo , Trastornos del Desarrollo del Lenguaje/orina , Discapacidad Intelectual Ligada al Cromosoma X/sangre , Discapacidad Intelectual Ligada al Cromosoma X/líquido cefalorraquídeo , Discapacidad Intelectual Ligada al Cromosoma X/orina , Trastornos del Movimiento/sangre , Trastornos del Movimiento/líquido cefalorraquídeo , Trastornos del Movimiento/genética , Trastornos del Movimiento/orina , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/sangre , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/líquido cefalorraquídeo , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/genética , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/orina , Proteínas Represoras/sangre , Proteínas Represoras/líquido cefalorraquídeo , Proteínas Represoras/orina , Trastornos del Habla/sangre , Trastornos del Habla/líquido cefalorraquídeo

RESUMEN

Deletion of the monoamine oxidase (MAO)-A and MAO-B was detected in two male siblings and in their mother. The approximately 800-kb deletion, extending from about 43.0MB to 43.8MB, was detected by array comparative genomic hybridization analysis. The MAOA and MAOB genes were included in the deletion, but the adjacent Norrie disease gene, NDP, was not deleted. The boys had short stature, hypotonia, severe developmental delays, episodes of sudden loss of muscle tone, exiting behavior, lip-smacking and autistic features. The serotonin levels in their cerebrospinal fluid were extremely elevated. Another set of siblings with this deletion was reported previously. We propose recognition of MAOA/B deletion syndrome as a distinct disorder.

Asunto(s)

Discapacidades del Desarrollo/complicaciones , Discapacidades del Desarrollo/genética , Monoaminooxidasa/deficiencia , Hipotonía Muscular/etiología , Catecolaminas/sangre , Catecolaminas/líquido cefalorraquídeo , Preescolar , Hibridación Genómica Comparativa , Discapacidades del Desarrollo/sangre , Discapacidades del Desarrollo/líquido cefalorraquídeo , Humanos , Masculino , Hipotonía Muscular/sangre , Hipotonía Muscular/líquido cefalorraquídeo , Hipotonía Muscular/genética , Serotonina/sangre , Serotonina/líquido cefalorraquídeo , Hermanos

RESUMEN

OBJECTIVE: We intended to investigate the effects of age, gender, and medications on amino acid cerebrospinal fluid (CSF)/plasma ratios in children, and to determine whether amino acid transports across the blood-CSF barrier in children differ from those in adults. PATIENTS AND METHODS: Amino acid concentrations measured by ion-exchange high-performance liquid chromatography were used (CSF from 99 children, simultaneously collected plasma from 76 children). Influence of age, gender, and medications on the amino acid CSF concentrations and CSF/plasma ratios were analyzed by linear multiple regression. Interactions of amino acid transports were analyzed by correlation analysis of CSF/plasma ratios. RESULTS: CSF/plasma ratios of serine, valine, histidine, and arginine were higher in younger children. The glutamate CSF/plasma ratio was higher in older children. Serine, alanine, threonine, valine, and histidine CSF/plasma ratios were lower in females. Glutamine, methionine, tyrosine, and phenylalanine CSF/plasma ratios were elevated with valproate therapy. Serine, threonine, valine, leucine, and tyrosine CSF/plasma ratios were lower with clobazam therapy. The asparagine CSF/plasma ratio was elevated with pyridoxal phosphate therapy. Transports of most essential neutral amino acids interacted with each other, as did neutral amino acids with low molecular weights. Cationic amino acids interacted with each other and some essential neutral amino acids. Acidic amino acids had no interactions with other amino acids. CONCLUSIONS: Age, gender, and anti-epileptic drugs affect amino acid CSF/plasma ratios in children. Transport interactions between amino acids in children showed no remarkable difference from those of adults and generally followed the substrate specificities of multiple amino acid transport systems.

Asunto(s)

Aminoácidos/sangre , Aminoácidos/líquido cefalorraquídeo , Discapacidades del Desarrollo/sangre , Discapacidades del Desarrollo/líquido cefalorraquídeo , Adolescente , Factores de Edad , Niño , Preescolar , Cromatografía Líquida de Alta Presión , Discapacidades del Desarrollo/tratamiento farmacológico , Femenino , Humanos , Lactante , Recién Nacido , Japón , Masculino , Valores de Referencia , Análisis de Regresión , Estudios Retrospectivos , Factores Sexuales

RESUMEN

Prospective studies of infants at risk for autism spectrum disorder have provided important clues about the early behavioural symptoms of autism spectrum disorder. Diagnosis of autism spectrum disorder, however, is not currently made until at least 18 months of age. There is substantially less research on potential brain-based differences in the period between 6 and 12 months of age. Our objective in the current study was to use magnetic resonance imaging to identify any consistently observable brain anomalies in 6-9 month old infants who would later develop autism spectrum disorder. We conducted a prospective infant sibling study with longitudinal magnetic resonance imaging scans at three time points (6-9, 12-15, and 18-24 months of age), in conjunction with intensive behavioural assessments. Fifty-five infants (33 'high-risk' infants having an older sibling with autism spectrum disorder and 22 'low-risk' infants having no relatives with autism spectrum disorder) were imaged at 6-9 months; 43 of these (27 high-risk and 16 low-risk) were imaged at 12-15 months; and 42 (26 high-risk and 16 low-risk) were imaged again at 18-24 months. Infants were classified as meeting criteria for autism spectrum disorder, other developmental delays, or typical development at 24 months or later (mean age at outcome: 32.5 months). Compared with the other two groups, infants who developed autism spectrum disorder (n = 10) had significantly greater extra-axial fluid at 6-9 months, which persisted and remained elevated at 12-15 and 18-24 months. Extra-axial fluid is characterized by excessive cerebrospinal fluid in the subarachnoid space, particularly over the frontal lobes. The amount of extra-axial fluid detected as early as 6 months was predictive of more severe autism spectrum disorder symptoms at the time of outcome. Infants who developed autism spectrum disorder also had significantly larger total cerebral volumes at both 12-15 and 18-24 months of age. This is the first magnetic resonance imaging study to prospectively evaluate brain growth trajectories from infancy in children who develop autism spectrum disorder. The presence of excessive extra-axial fluid detected as early as 6 months and the lack of resolution by 24 months is a hitherto unreported brain anomaly in infants who later develop autism spectrum disorder. This is also the first magnetic resonance imaging evidence of brain enlargement in autism before age 2. These findings raise the potential for the use of structural magnetic resonance imaging to aid in the early detection of children at risk for autism spectrum disorder or other neurodevelopmental disorders.

Asunto(s)

Encéfalo/crecimiento & desarrollo , Encéfalo/patología , Trastornos Generalizados del Desarrollo Infantil/líquido cefalorraquídeo , Trastornos Generalizados del Desarrollo Infantil/complicaciones , Discapacidades del Desarrollo/patología , Factores de Edad , Preescolar , Discapacidades del Desarrollo/líquido cefalorraquídeo , Femenino , Lateralidad Funcional , Cabeza/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Lactante , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Factores de Tiempo

RESUMEN

BACKGROUND: Primary or secondary abnormalities of glycosylation have been reported in various brain diseases. Decreased asialotransferrin to sialotransferrin ratio in cerebrospinal fluid (CSF) is a diagnostic marker of leukodystrophies related to mutations of genes encoding translation initiation factor, EIF2B. We investigated the CSF glycome of eIF2B-mutated patients and age-matched normal individuals in order to further characterize the glycosylation defect for possible use as a biomarker. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a differential N-glycan analysis using MALDI-TOF/MS of permethylated N-glycans in CSF and plasma of controls and eIF2B-mutated patients. We found in control CSF that tri-antennary/bisecting and high mannose structures were highly represented in samples obtained between 1 to 5 years of age, whereas fucosylated, sialylated structures were predominant at later age. In CSF, but not in plasma, of eIF2B-mutated patient samples, we found increased relative intensity of bi-antennary structures and decreased tri-antennary/bisecting structures in N-glycan profiles. Four of these structures appeared to be biomarker candidates of glycomic profiles of eIF2B-related disorders. CONCLUSION: Our results suggest a dynamic development of normal CSF N-glycan profiles from high mannose type structures to complex sialylated structures that could be correlated with postnatal brain maturation. CSF N-glycome analysis shows relevant quantitative changes associated with eIF2B related disorders. This approach could be applied to other neurological disorders involving developmental gliogenesis/synaptogenesis abnormalities.

Asunto(s)

Biomarcadores/metabolismo , Encefalopatías/líquido cefalorraquídeo , Encefalopatías/genética , Líquido Cefalorraquídeo/metabolismo , Discapacidades del Desarrollo/líquido cefalorraquídeo , Discapacidades del Desarrollo/genética , Factor 2B Eucariótico de Iniciación/genética , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/líquido cefalorraquídeo , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/genética , Mutación , Polisacáridos/química , Calibración , Preescolar , Femenino , Glicosilación , Humanos , Lactante , Masculino , Metilación , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos

RESUMEN

Mitochondrial disorders are varied in their clinical presentation and pathogenesis. Diagnosis is usually made clinically and genetic defects are often not identified. We present a 6-year-old female patient with a diagnosis of a mitochondrial disorder secondary to complex I deficiency with seizures and developmental delay from infancy. Glucose transporter deficiency was suspected after a lumbar puncture showed hypoglycorrhachia. Her disorder was confirmed genetically as a mutation in her solute carrier family 2, facilitated glucose transporter member 1 (SLCA2) gene. Delayed diagnosis led to delayed treatment, and neurologic sequelae may have been prevented by earlier recognition of this disorder.

Asunto(s)

Errores Innatos del Metabolismo de los Carbohidratos/complicaciones , Errores Innatos del Metabolismo de los Carbohidratos/genética , Discapacidades del Desarrollo/genética , Transportador de Glucosa de Tipo 2/deficiencia , Enfermedades Mitocondriales/etiología , Enfermedades Mitocondriales/genética , Errores Innatos del Metabolismo de los Carbohidratos/líquido cefalorraquídeo , Niño , Discapacidades del Desarrollo/líquido cefalorraquídeo , Discapacidades del Desarrollo/complicaciones , Femenino , Glucosa/líquido cefalorraquídeo , Humanos , Enfermedades Mitocondriales/líquido cefalorraquídeo , Punción Espinal

RESUMEN

Although patients with low cerebrospinal fluid (CSF) serotonin metabolite levels have been reported, inborn errors of the rate-limiting enzyme of serotonin synthesis (tryptophan hydroxylase, TPH) have not been described so far. In this study we aimed to evaluate CSF alterations of the serotonin metabolite 5-hydroxyindolacetic acid (5-HIAA) in patients with neurological disorders and to explore a possible TPH deficiency in some of them. A total of 606 patients (286 males, 320 females, mean age 4 years and 6 months, SD 5 years and 7 months) underwent CSF analysis of neurotransmitter metabolites by reverse phase high performance liquid chromatography. Results were compared with values established in a control population. Patients' medical records were reviewed to determine diagnosis and clinical features. A primary defect of biogenic amines was genetically investigated in indicated patients. Low 5-HIAA was seen in 19.3%. Of these, 22.2% showed inborn errors of metabolism (mitochondrial disorders being the most frequent at 10.2% of low 5-HIAA patients) and neurogenetic conditions. Other relatively frequent conditions were pontocerebellar hypoplasia (4.3%), Rett syndrome (4.3%), and among congenital nonetiologically determined conditions, epilepsy including epileptic encephalopathies (26.4%), leukodystrophies (6.8%), and neuropsychiatric disturbances (4.2%). Mutational analysis of the TPH2 gene, performed in five candidate patients, was negative. Although frequency of secondary alteration of 5-HIAA was relatively high in patients with neurological disorders, this finding was more frequently associated with some neurometabolic disorders, epileptic encephalopathies, and neuropsychiatric disturbances. No inborn errors of TPH were found. Due to serotonin's neurotrophic role and to ameliorate symptoms, a supplementary treatment with 5-hydroxytriptophan would seem advisable in these patients.

Asunto(s)

Ácido Hidroxiindolacético/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Estudios de Casos y Controles , Niño , Preescolar , Análisis Mutacional de ADN , Discapacidades del Desarrollo/líquido cefalorraquídeo , Discapacidades del Desarrollo/genética , Femenino , Humanos , Ácido Hidroxiindolacético/metabolismo , Lactante , Recién Nacido , Masculino , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/metabolismo , Serotonina/metabolismo , Triptófano Hidroxilasa/genética

RESUMEN

Glucose transporter type 1 (GLUT1) deficiency syndrome is a rare, treatable cause of developmental delay and seizures. It must be considered in the differential diagnosis of infants with intractable seizures. The finding of a low glucose level in the cerebrospinal fluid with normal level in the blood in the absence of pleocytosis or other cerebrospinal fluid abnormalities identifies the condition. Genetic analysis for confirmation is available. Treatment with antiepileptic medications often is unsuccessful, and the ketogenic diet is the favored treatment for seizure control. Early identification and initiation of treatment may prevent or lessen the severity of developmental delay.

Asunto(s)

Discapacidades del Desarrollo/patología , Transportador de Glucosa de Tipo 1/deficiencia , Convulsiones/patología , Niño , Discapacidades del Desarrollo/líquido cefalorraquídeo , Discapacidades del Desarrollo/terapia , Dieta Cetogénica , Femenino , Glucosa/líquido cefalorraquídeo , Humanos , Lactante , Masculino , Convulsiones/líquido cefalorraquídeo , Convulsiones/terapia , Síndrome

RESUMEN

The authors describe a 6-year-old girl with developmental delay, psychomotor regression, seizures, mental retardation, and autistic features associated with low CSF levels of 5-methyltetrahydrofolate, the biologically active form of folates in CSF and blood. Folate and B12 levels were normal in peripheral tissues, suggesting cerebral folate deficiency. Treatment with folinic acid corrected CSF abnormalities and improved motor skills.

Asunto(s)

Trastorno Autístico/tratamiento farmacológico , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/crecimiento & desarrollo , Discapacidades del Desarrollo/tratamiento farmacológico , Deficiencia de Ácido Fólico/tratamiento farmacológico , Leucovorina/administración & dosificación , Convulsiones/tratamiento farmacológico , Adaptación Fisiológica/efectos de los fármacos , Adaptación Fisiológica/fisiología , Trastorno Autístico/líquido cefalorraquídeo , Trastorno Autístico/etiología , Corteza Cerebral/metabolismo , Niño , Discapacidades del Desarrollo/líquido cefalorraquídeo , Discapacidades del Desarrollo/etiología , Progresión de la Enfermedad , Femenino , Ácido Fólico/metabolismo , Deficiencia de Ácido Fólico/líquido cefalorraquídeo , Deficiencia de Ácido Fólico/fisiopatología , Predisposición Genética a la Enfermedad , Humanos , Discapacidad Intelectual/tratamiento farmacológico , Discapacidad Intelectual/etiología , Discapacidad Intelectual/metabolismo , Mutación/genética , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Proteína Portadora de Folato Reducido/genética , Convulsiones/líquido cefalorraquídeo , Convulsiones/etiología , Tetrahidrofolatos/líquido cefalorraquídeo , Factores de Transcripción/genética , Resultado del Tratamiento

RESUMEN

The authors report the unusual clinical and neurophysiologic features of a sporadic case of a boy carrying an 806delG mutation on the MECP2 gene. A 28-month-old boy was examined for severe developmental delay, seizures, microcephaly, breathing dysfunction, and spontaneous and evoked myoclonic jerks of upper limbs. Neurophysiologic study proved the cortical origin of myoclonus; however, it was not associated with signs of cortical hyperexcitability. 3-Methoxy-4-hydroxy-phenylethylene glycol and valine concentrations were low in CSF.

Asunto(s)

Proteínas Cromosómicas no Histona/genética , Proteínas de Unión al ADN/genética , Discapacidades del Desarrollo/genética , Epilepsias Parciales/genética , Epilepsia Tónico-Clónica/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Epilepsia Mioclónica Juvenil/genética , Proteínas Represoras/genética , Proteínas Cromosómicas no Histona/deficiencia , Codón sin Sentido , Análisis Mutacional de ADN , Proteínas de Unión al ADN/deficiencia , Discapacidades del Desarrollo/líquido cefalorraquídeo , Discapacidades del Desarrollo/fisiopatología , Electroencefalografía , Electromiografía , Epilepsia Tónico-Clónica/líquido cefalorraquídeo , Epilepsia Tónico-Clónica/fisiopatología , Potenciales Evocados Somatosensoriales , Enfermedades Genéticas Ligadas al Cromosoma X/líquido cefalorraquídeo , Enfermedades Genéticas Ligadas al Cromosoma X/clasificación , Enfermedades Genéticas Ligadas al Cromosoma X/diagnóstico , Enfermedades Genéticas Ligadas al Cromosoma X/fisiopatología , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Metoxihidroxifenilglicol/líquido cefalorraquídeo , Proteína 2 de Unión a Metil-CpG , Microcefalia/genética , Epilepsia Mioclónica Juvenil/líquido cefalorraquídeo , Epilepsia Mioclónica Juvenil/fisiopatología , Trastornos Psicomotores/líquido cefalorraquídeo , Trastornos Psicomotores/genética , Trastornos Psicomotores/fisiopatología , Trastornos Respiratorios/genética , Síndrome de Rett/genética , Eliminación de Secuencia , Factores Sexuales , Estado Epiléptico/etiología , Grabación en Video

RESUMEN

Neuronal ceroid-lipofuscinoses (NCL) are a group of neurodegenerative disorders. There is much evidence for a role of peroxidation processes in the pathogenesis of NCL, although this would certainly be indirect. Reduced total antioxidant activity of cerebrospinal fluid (CSF) has been reported in NCL. Since ascorbic acid represents a major antioxidant in CSF, we have now determined this parameter in CSF of two patients with the infantile form of NCL (Santavuori-Haltia disease). However, the ascorbic acid values obtained (103.6 and 181.3 microM) are comparable with control values from the literature as well as with those measured in groups of children with neurologic/psychiatric diseases other than NCL (mean +/- standard deviation: 137.1+/-41.3 microM), with suspected (but excluded) meningitis (124.1+/-34.0 microM) and acute lymphoblastic leukemia (131.7+/-17.0 microM). Our results indicate that CSF ascorbic acid concentrations are not affected by peroxidation processes in infantile NCL, but reveal a sharply decreased ascorbic acid concentration in one of the non-NCL patients, possibly associated with his convulsions and/or his anticonvulsant therapy.

Asunto(s)

Ácido Ascórbico/líquido cefalorraquídeo , Lipofuscinosis Ceroideas Neuronales/líquido cefalorraquídeo , Niño , Preescolar , Discapacidades del Desarrollo/líquido cefalorraquídeo , Discapacidades del Desarrollo/complicaciones , Femenino , Humanos , Lactante , Masculino , Trastornos Mentales/líquido cefalorraquídeo , Trastornos Mentales/complicaciones , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/complicaciones , Valores de Referencia

RESUMEN

Using a two-site enzyme-linked immunosorbent assay, we measured nerve growth factor (NGF) levels in cerebrospinal fluid (CSF) from 40 patients with or without brain atrophy due to various neurologic disorders. White matter and cortical atrophies were assessed by frontal horn index (FHI) and subarachnoid space area/inner skull space area (SSA/ISSA) ratio, respectively. CT findings of 40 patients were classified into 4 grades: normal (< mean + 2SD), grade I (mean + 2SD < or = or < mean + 4SD), grade II (mean + 4SD < or = < mean + 8SD), and grade III (mean + 8SD < or =). NGF levels in CSF were significantly elevated in 3 of 6 patients with grade III cortical atrophy and normal in 2 with grade II atrophy, 4 with grade I atrophy and 28 without atrophy. Cortical atrophy was progressive in the 3 with NGF elevation in CSF. With respect to white matter atrophy, NGF elevation was observed in none of 3 with grade III white matter atrophy, two of 4 with grade II atrophy, none of 3 with grade I atrophy and one of 30 without atrophy. The symptoms of the two of three with NGF elevation were progressive at the time of obtaining the CSF samples, while those of other patients without NGF elevation were non-progressive. The present study suggests that NGF elevation in CSF may reflect extensive cortical degenerative change.

Asunto(s)

Encefalopatías/líquido cefalorraquídeo , Corteza Cerebral/patología , Factores de Crecimiento Nervioso/líquido cefalorraquídeo , Enfermedades Neurodegenerativas/líquido cefalorraquídeo , Adolescente , Atrofia/líquido cefalorraquídeo , Encefalopatías/patología , Estudios de Casos y Controles , Niño , Preescolar , Estudios Transversales , Discapacidades del Desarrollo/líquido cefalorraquídeo , Discapacidades del Desarrollo/patología , Progresión de la Enfermedad , Femenino , Humanos , Lactante , Masculino , Fibras Nerviosas Mielínicas/patología , Enfermedades Neurodegenerativas/patología , Índice de Severidad de la Enfermedad

Asunto(s)

Ácido gamma-Aminobutírico/líquido cefalorraquídeo , Aldehído Oxidorreductasas/deficiencia , Anticonvulsivantes/uso terapéutico , Errores Innatos del Metabolismo de los Carbohidratos/líquido cefalorraquídeo , Errores Innatos del Metabolismo de los Carbohidratos/tratamiento farmacológico , Niño , Discapacidades del Desarrollo/líquido cefalorraquídeo , Discapacidades del Desarrollo/tratamiento farmacológico , Cromatografía de Gases y Espectrometría de Masas , Humanos , Masculino , Técnica de Dilución de Radioisótopos , Succionato-Semialdehído Deshidrogenasa , Vigabatrin , Ácido gamma-Aminobutírico/análogos & derivados , Ácido gamma-Aminobutírico/uso terapéutico

RESUMEN

We measured concentrations of 3-methoxy-4-hydroxy-phenylglycol, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid--the metabolites of noradrenaline, dopamine, and serotonin used as central neurotransmitters--in the cerebrospinal fluid (CSF) specimens of five girls with Rett syndrome. These patients met the clinical criteria for both inclusion and exclusion of the diagnosis of Rett syndrome. In contrast to previous reports, cerebral monoamine metabolites were present in normal concentrations in CSF. In addition, concentrations of gamma-aminobutyric acid and of a large number of other amino acids and related compounds were normal in the CSF of patients with the syndrome. We doubt that an underlying biochemical cause for this disorder has yet been discovered.

Asunto(s)

Aminas Biogénicas/metabolismo , Encefalopatías/líquido cefalorraquídeo , Trastornos de la Conducta Infantil/líquido cefalorraquídeo , Discapacidades del Desarrollo/líquido cefalorraquídeo , Trastornos Mentales/líquido cefalorraquídeo , Adolescente , Aminas Biogénicas/líquido cefalorraquídeo , Encefalopatías/metabolismo , Niño , Trastornos de la Conducta Infantil/metabolismo , Preescolar , Discapacidades del Desarrollo/metabolismo , Femenino , Humanos , Trastornos Mentales/metabolismo , Valores de Referencia , Síndrome , Ácido gamma-Aminobutírico/líquido cefalorraquídeo