RESUMEN
Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited heterogeneous neurodegenerative rare disorders. These patients present with dystonia, spasticity, parkinsonism and neuropsychiatric disturbances, along with brain magnetic resonance imaging (MRI) evidence of iron accumulation. In sum, they are devastating disorders and to date, there is no specific treatment. Ten NBIA genes are accepted: PANK2, PLA2G6, C19orf12, COASY, FA2H, ATP13A2, WDR45, FTL, CP, and DCAF17; and nonetheless, a relevant percentage of patients remain without genetic diagnosis, suggesting that other novel NBIA genes remain to be discovered. Overlapping complex clinical pictures render an accurate differential diagnosis difficult. Little is known about the pathophysiology of NBIAs. The reported NBIA genes take part in a variety of pathways: CoA synthesis, lipid and iron metabolism, autophagy, and membrane remodeling. The next-generation sequencing revolution has achieved relevant advances in genetics of Mendelian diseases and provide new genes for NBIAs, which are investigated according to 2 main strategies: genes involved in disorders with similar phenotype and genes that play a role in a pathway of interest. To achieve an effective therapy for NBIA patients, a better understanding of the biological process underlying disease is crucial, moving toward a new age of precision medicine.
Asunto(s)
Encéfalo/diagnóstico por imagen , Hierro/metabolismo , Enfermedades Neurodegenerativas/genética , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Encéfalo/fisiopatología , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Metabolismo de los Lípidos/genética , Imagen por Resonancia Magnética , Enfermedades Neurodegenerativas/diagnóstico , Enfermedades Neurodegenerativas/diagnóstico por imagen , Enfermedades Neurodegenerativas/fisiopatología , Neurodegeneración Asociada a Pantotenato Quinasa/diagnóstico , Neurodegeneración Asociada a Pantotenato Quinasa/diagnóstico por imagen , Neurodegeneración Asociada a Pantotenato Quinasa/fisiopatologíaRESUMEN
UNLABELLED: PMM2-CDG, the most frequent congenital disorder of N-glycosylation, is an autosomal recessive disease with a multisystem presentation. PMM2-CDG patients show an increased risk for thrombosis, which might be in part due to spontaneous platelet aggregations as previously described. A potential hypoglycosylation of platelet proteins in these patients might explain this increased reactivity, as removal of sialic acid from platelets, particularly of GPIbα, leads to enhance platelet aggregation and clearance from the circulation. This study is the first one that has evaluated the glycosylation status of platelet proteins in 6 PMM2-CDG patients using different approaches including immunoblot, RCA120 lectin binding to platelets and expression of different membrane platelet N-glycoproteins by flow cytometry, as well as by platelet N-glycoproteome analysis. RCA120 lectin binding to the platelet membrane of PMM2-CDG patients showed evidence for decreased sialic acid content. However, immunoblot and flow cytometric analysis of different platelet N-glycoproteins, together with the more sensitive 2D-DIGE analysis, suggest that platelet N-glycoproteins, including GPIbα, seem to be neither quantitatively nor qualitatively significantly affected. The increased binding of RCA120 lectin could be explained by the abnormal glycosylation of hepatic proteins being attached to the platelets. CONCLUSIONS: This is the first study that has evaluated the platelet N-glycoproteome. Our findings suggest that platelet proteins are not significantly affected in PMM2-CDG patients. Further studies are still warranted to unravel the mechanism(s) that increase(s) the risk of thrombosis in these patients.
Asunto(s)
Trastornos Congénitos de Glicosilación/sangre , Glicoproteínas de Membrana Plaquetaria/análisis , Estudios de Casos y Controles , Glicosilación , Humanos , Glicoproteínas de Membrana Plaquetaria/metabolismo , ProteómicaRESUMEN
INTRODUCTION: Oculogyric crises are considered to be a form of focal dystonia and can be observed as reactions to pharmaceuticals. The signs and symptoms may be confused with epileptic crises. AIMS: To describe the clinical features and progress of patients with pharmaceutical-related oculogyric crises and to carry out a review of the topic. CASE REPORTS: We conducted a retrospective, descriptive study of four patients evaluated in the neurology service due to oculogyric crises. The patients had been diagnosed with an associated conduct disorder requiring treatment with antipsychotic drugs. The episodes of oculogyric crises did not correlate with the findings in the electroencephalogram. They responded well to the reduction in dosage or to withdrawal of the apparent causing agent. CONCLUSIONS: The clinical picture does not present only in patients treated with antipsychotics but is also linked with other pharmaceuticals that are frequently used in daily paediatric practice. When oculogyric crises are the reason for visiting, differential diagnoses must be taken into account in order to avoid unnecessary studies and to carry out an appropriate therapeutic management.
Asunto(s)
Antipsicóticos/efectos adversos , Antagonistas de Dopamina/efectos adversos , Discinesia Inducida por Medicamentos/etiología , Trastornos Distónicos/inducido químicamente , Trastornos de la Motilidad Ocular/inducido químicamente , Adolescente , Anticonvulsivantes , Aripiprazol , Niño , Trastornos de la Conducta Infantil/complicaciones , Trastornos de la Conducta Infantil/tratamiento farmacológico , Preescolar , Dopamina/fisiología , Síndrome de Down/complicaciones , Electroencefalografía , Epilepsia/complicaciones , Epilepsia/tratamiento farmacológico , Femenino , Síndrome del Cromosoma X Frágil/complicaciones , Humanos , Discapacidad Intelectual/complicaciones , Isoxazoles/efectos adversos , Masculino , Metotrimeprazina , Palmitato de Paliperidona , Piperazinas/efectos adversos , Pirimidinas/efectos adversos , Quinolonas/efectos adversos , Risperidona/efectos adversos , Síndrome de Abstinencia a Sustancias/etiología , Translocación Genética , Ácido ValproicoRESUMEN
Hypokinetic-rigid syndrome (HRS) or "parkinsonism" is rare in children. From a clinical point of view it is characterised by a group of signs in which hypokinesia (decreased number of movements), bradykinesia (slowness of movements), rigidity and rest tremor are the fundamental traits. Nervous system infections, immunomediated encephalitis, hypoxia and some drugs have been described as acquired or secondary causes of HRS in the paediatric age. Inborn errors of metabolism (IEM) comprise and important group regarding genetic causes. Main diseases causing HRS in children are neurotransmitter (biogenic amines) defects, metal storage diseases, energy metabolism disorders and lysosomal diseases. In general, in IEM, the HRS is associated to other neurological signs such as dykinesias, pyramidal signs, and psychomotor delay, is very rare in the neonatal period, tends to be more frequent in advanced stages of progressive diseases, and may respond to specific therapies. In particular, l-dopa + carbidopa can be a very effective treatment in neurotransmitter defects, whereas other disorders such as Wilson disease and some particular lysosomal disorders have different therapeutic possibilities. Furthermore, other genetic conditions in dopa-responsive and non-responsive HRS should be also considered, especially in juvenile parkinsonism. Through this review, a practical orientation for paediatric neurologists concerning clinical clues, diagnostic procedure and treatment of metabolic HRS will be provided.
Asunto(s)
Encefalopatías Metabólicas Innatas/fisiopatología , Hipocinesia/metabolismo , Rigidez Muscular/metabolismo , Trastornos Parkinsonianos/metabolismo , Encefalopatías Metabólicas Innatas/diagnóstico , Encefalopatías Metabólicas Innatas/metabolismo , Niño , Diagnóstico Diferencial , Humanos , Hipocinesia/diagnóstico , Hipocinesia/fisiopatología , Rigidez Muscular/diagnóstico , Rigidez Muscular/fisiopatología , Trastornos Parkinsonianos/diagnóstico , Trastornos Parkinsonianos/fisiopatología , SíndromeRESUMEN
OBJECTIVES: To analyze the association between ammonia and glutamine used for metabolic control in inherited urea cycle disorders (UCD) in a large series of patients. DESIGN AND METHODS: Paired plasma amino acid-ammonia data from 26 UCD patients were analyzed (n=921). RESULTS: Increased plasma glutamine values were consistently observed in UCD patients, despite normal plasma ammonia concentrations, especially for mitochondrial UCD. CONCLUSIONS: Further therapeutic efforts are probably needed to control increased glutamine values, considering their potentially neurotoxic effect.
Asunto(s)
Amoníaco/sangre , Glutamina/sangre , Trastornos Innatos del Ciclo de la Urea/sangre , Humanos , Recién NacidoRESUMEN
Hereditary cystathioninuria is due to mutations in the CTH gene that encodes for cystathionase, a pyridoxal-5'-phosphate (PLP) dependent enzyme. To date, mutations in this gene have been described in 10 unrelated cystathioninuric patients. Enzyme assays have showed that mutated cystathionase exhibits lower activity than controls. As cystathioninuria is usually accompanied by a wide variety of symptoms, it has been questioned whether it is a disease or just a biochemical finding not associated with the clinical picture of these patients. This is the first report of Spanish patients with cystathioninuria and mild to severe neurological symptoms in childhood. After oral pyridoxine therapy biochemical parameters have normalized but clinical amelioration was not evident. All patients were homozygotes for the c.200C>T (p.T67I) variant which is the most prevalent inactivating mutation in the CTH gene. To further investigate the history of the alleles carrying the c.200C>T transition in Europe, we also constructed the haplotypes on the CTH locus in our Spanish patients as well as in a clinical series of cystathioninuric patients from the Czech Republic harboring the same nucleotide change. We suggest that the CTH p.T67I substitution could have an ancient common origin, which probably occurred in the Neolithic Era and spread throughout Europe.
Asunto(s)
Alelos , Cistationina gamma-Liasa/genética , Variación Genética/genética , Niño , Preescolar , República Checa , Europa (Continente) , Femenino , Humanos , Hiperhomocisteinemia/genéticaRESUMEN
Methylenetetrahydrofolate reductase (MTHFR) plays a major role in folate metabolism. Disturbed function of the enzyme results in hyperhomocysteinemia and causes severe vascular and neurological disorders and developmental delay. Five patients suspected of having non-classical homocystinuria due to MTHFR deficiency were examined with respect to their symptoms, MTHFR enzyme activity and genotypes of the MTHFR gene. All patients presented symptoms of severe central nervous system disease. Two patients died, at the ages of 15 months and 14 years. One patient is currently 32 years old, and is being treated with betaine and folinic acid. The other two patients, with an early diagnosis and a severe course of the disease, are currently improving under treatment. MTHFR enzyme activity in the fibroblasts of four of the patients was practically undetectable. We found four novel mutations, three of which were missense changes c.664G> T (p.V218L), c.1316T> C (p.F435S) and c.1733T> G (p.V574G), and the fourth was the 1-bp deletion c.1780delC (p.L590CfsX72). We also found the previously reported nonsense mutation c.1420G> T (p.E470X). All the patients were homozygous. Molecular modelling of the double mutant allele (p.V218L; p.A222V) revealed that affinity for FAD was not affected in this mutant. For the p.E470X mutation, the evidence pointed to nonsense-mediated mRNA decay. In general, genotype-phenotype analysis predicts milder outcomes for patients with missense changes than for those in which mutations led to severe alterations of the MTHFR protein.
Asunto(s)
Homocistinuria/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/deficiencia , Adolescente , Adulto , Betaína/uso terapéutico , Preescolar , Resultado Fatal , Femenino , Homocistinuria/tratamiento farmacológico , Homocistinuria/enzimología , Humanos , Lactante , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Metilenotetrahidrofolato Reductasa (NADPH2)/metabolismo , Modelos Moleculares , Tetrahidrofolatos/uso terapéutico , TermodinámicaRESUMEN
Motor disturbances are very common in paediatric neurology. Often families can be reassured that these are just variants of normal development. However, abnormal movements can also be the hallmark of severe brain dysfunction of different and complex origins. This review concentrates on motor disturbances as frequent and important symptoms of inborn errors of metabolism. A structured diagnostic approach is developed taking into account age-dependent physiological developments and pathophysiological responses of gross and fine motor functions. A series of investigations are presented with the primary aim of early diagnosis of treatable conditions. The correct recognition and differentiation of movement disorders (ataxia, rigid akinetic syndrome (Fparkinsonism_), dystonia, athetosis, tremor,and others), spasticity, and neuromuscular disorders, requires profound neurological expertise. A high level of suspicion and close interaction between paediatric neurologists and specialists in inborn errors of metabolism are indispensable to effectively and timely identify patients in whom motor disturbances are the presenting and/or main symptom of an inborn error.
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Errores Innatos del Metabolismo/complicaciones , Errores Innatos del Metabolismo/diagnóstico , Enfermedad de la Neurona Motora/etiología , Algoritmos , Niño , Diagnóstico Diferencial , Humanos , Enfermedad de la Neurona Motora/diagnóstico , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/etiología , Espasticidad Muscular/diagnóstico , Espasticidad Muscular/etiología , Enfermedades del Sistema Nervioso Periférico/diagnósticoRESUMEN
In countries where clinical phenylketonuria is detected by newborn screening inborn errors of metabolism are rare causes of isolated mental retardation. There is no international agreement about what type of metabolic tests must be applied in patients with unspecific mental retardation. However, and although infrequent, there are a number of inborn errors of metabolism that can present in this way. Because of the high recurrence risk and the possibility of specific therapies, guidelines need to be developed and adapted to different populations. The application of a universal protocol may result in a low diagnostic performance in individual ethnic populations. Consideration of associated signs (extraneurological manifestations, psychiatric signs, autistic traits, cerebellar dysfunction, epilepsy or dysmorphic traits) greatly improves the diagnostic fulfilment.
Asunto(s)
Discapacidad Intelectual/etiología , Errores Innatos del Metabolismo/complicaciones , Algoritmos , Humanos , Recién Nacido , Discapacidad Intelectual/diagnóstico , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/psicología , Tamizaje Neonatal/métodos , Guías de Práctica Clínica como AsuntoRESUMEN
Congenital disorder of glycosylation Ia (CDG-Ia) is a metabolic disease with a broad spectrum of clinical signs, including recently described mild phenotypes. Our aim was to describe the clinical presentation and follow-up of eight CDG-Ia patients highlighting atypical features and aspects of evolution of the disease. CDG diagnosis was confirmed by enzymatic analysis of phosphomannomutase (PMM2) and molecular studies of the PMM2 gene. Four neonates presented with cerebral haemorrhage (1), failure to thrive (2) and non-immune hydrops (1) and a fatal course to death (2); pathological examination of the brain in one case revealed olivopontocerebellar atrophy of prenatal origin. During infancy failure to thrive, coagulopathy and hepatopathy were the most significant causes of morbidity, but these disappeared after the first years of life in most patients. Three patients are currently in their 20s; they present mental retardation and severe motor impairment but no acute decompensations were noticed after the first decade of life. They do not present spinal or thoracic deformities otherwise observed in patients from northern countries. A 10-year-old patient who manifested gastrointestinal dysfunction in early childhood showed normal neurodevelopment. Mutation analysis of the PMM2 gene showed great variability, with all patients being compound heterozygous for two different mutations. Long-term evolution in our patients indicates that CDG-Ia is a stable systemic and neurological condition after the first decade of life. The diverse phenotypes and atypical manifestations in our series may be due to their genetic heterogeneity.
Asunto(s)
Trastornos Congénitos de Glicosilación/patología , Adolescente , Adulto , Envejecimiento/fisiología , Encéfalo/anomalías , Encéfalo/patología , Niño , Preescolar , Trastornos Congénitos de Glicosilación/genética , Trastornos Congénitos de Glicosilación/mortalidad , Análisis Mutacional de ADN , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Lactante , Recién Nacido , Riñón/anomalías , Imagen por Resonancia Magnética , Masculino , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/fisiopatología , Convulsiones/etiología , España , Tomografía Computarizada por Rayos X , Transferrina/metabolismo , Adulto JovenRESUMEN
Neurotransmitters are essential in young children for differentiation and neuronal growth of the developing nervous system. We aimed to identify possible factors related to secondary neurotransmitter abnormalities in pediatric patients with neurological disorders. We analyzed cerebrospinal fluid (CSF) and biogenic amine metabolites in 56 infants (33 males, 23 females; mean age 5.8mo [SD 4.1mo] range 1d-1y) with neurological disorders whose aetiology was initially unknown. Patients were classified into three clinical phenotypes: epileptic encephalopathy, severe motor impairment, and non-specific manifestations. All patients showed normal results for screening of inborn errors of metabolism. We report clinical, neuroimaging, and follow-up data. Among the patients studied, 10 had low homovanillic acid (HVA) levels and in four patients, 5-hydroxyindoleacetic acid (5-HIAA) was also reduced. Patients with neonatal onset had significantly lower levels of HVA than a comparison group. HVA deficiency was also associated with severe motor impairment and the final diagnosis related to neurodegenerative disorders. 5-HIAA values tended to be decreased in patients with brain cortical atrophy. The possibility of treating patients with L-Dopa and 5-hydroxytryptophan, in order to improve their neurological function and maturation, may be considered.
Asunto(s)
5-Hidroxitriptófano/líquido cefalorraquídeo , Encéfalo/patología , Epilepsia , Ácido Homovanílico/líquido cefalorraquídeo , Ácido Hidroxiindolacético/líquido cefalorraquídeo , Trastornos de la Destreza Motora , Enfermedades del Sistema Nervioso , Pterinas/líquido cefalorraquídeo , Atrofia/patología , Electroencefalografía , Epilepsia/líquido cefalorraquídeo , Epilepsia/diagnóstico , Epilepsia/etiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Trastornos de la Destreza Motora/líquido cefalorraquídeo , Trastornos de la Destreza Motora/etiología , Trastornos de la Destreza Motora/fisiopatología , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/complicaciones , Enfermedades del Sistema Nervioso/diagnóstico , Fenotipo , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION AND DEVELOPMENT: Isolated mental retardation is rarely caused by metabolic factors. The application of a standardised protocol offers low diagnostic performance. There is no international agreement about what type of metabolic examination must be applied in patients with unspecific mental retardation. Nevertheless, and although they are infrequent, there are a number of inborn errors of metabolism that can present in this way. Urea cycle disorders, different forms of homocystinuria, creatine transport deficiency, 4-hydroxybutyric aciduria, Sanfilippo disease, adenylosuccinate lyase deficit and certain extraordinarily rare congenital disorders of the glycosylation of proteins are some examples of them. It is important first to consider those for which treatment is available and that could be diagnosed genetically for possible family counselling. CONCLUSIONS: Rather than applying a standardised study protocol it is essential is to perform a thorough appraisal of the signs and symptoms associated with the mental retardation (psychiatric disorders, autistic traits, predominant compromise of language, signs of cerebellar dysfunction, epilepsy, dysmorphic traits), since in most disorders it is necessary to apply specific analyses, which are not included in conventional metabolic studies and are only available in certain reference centres.
Asunto(s)
Encefalopatías Metabólicas/complicaciones , Discapacidad Intelectual/etiología , Algoritmos , Humanos , Discapacidad Intelectual/diagnósticoRESUMEN
BACKGROUND: Although phenylketonuria is a treatable disease, patients with late or nonoptimal phenylalanine-restricted diet may experience brain damage. The authors used tridimensional MRI and a voxelwise analysis method to investigate possible volume changes in the brain parenchyma of patients with phenylketonuria. METHODS: The authors assessed 27 treated patients (mean age +/- SD, 20 +/- 7 years) and 27 matched control subjects. Global tissue volumes were compared, and statistical parametric maps of between-group regional volume differences were obtained for gray and white matter. Anatomic data were correlated with relevant clinical and biochemical variables. RESULTS: Patients with phenylketonuria showed smaller gray matter volumes that were associated with lower IQ and older age at diagnosis. Voxel-based maps revealed that significant gray matter volume reduction occurred in motor and premotor cortex and thalamus. A relative increase in gray matter volume was observed in the ventral part of the striatum. The authors found no group differences for global white matter measurements. Higher recent phenylalanine levels, however, were associated with larger global white matter volume in early-treated patients. Voxel-based maps showed a relative volume reduction in periventricular white matter and a relative increase in the region of the internal capsule, extending to the adjacent thalamus and striatum. CONCLUSIONS: Treated patients may show significant gray and white matter volume changes related to the duration and strict observation of dietary treatment. Further studies are needed to investigate whether the presence of neurologic symptoms may be explained by specific anatomic alterations.
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Encéfalo/anatomía & histología , Encéfalo/patología , Fenilcetonurias/patología , Adolescente , Adulto , Niño , Femenino , Humanos , Inteligencia , Imagen por Resonancia Magnética , Masculino , Fenilcetonurias/psicología , Valores de ReferenciaAsunto(s)
Enfermedades Cerebelosas/complicaciones , Hidrocefalia/etiología , Adolescente , Adulto , Enfermedades Cerebelosas/diagnóstico , Enfermedades Cerebelosas/patología , Enfermedades Cerebelosas/fisiopatología , Niño , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , MasculinoRESUMEN
AIMS: The aim of this work is to describe the clinical, biochemical and genetic characteristics of neurotransmitter diseases at the paediatric age, together with possible forms of treatment. We also sought to determine the diagnostic methodology of these disorders (collection and analysis of samples). DEVELOPMENT: These diseases essentially consist of a deficit of biogenic amines and alterations in GABA metabolism (gamma-aminobutyric acid). Disorders affecting the neurotransmission of biogenic amines often present in the form of hypokinesia, trunk hypotonia with increased limb tone, oculogyric crises, ptosis, faulty temperature regulation or abnormal movements. Defects in GABA metabolism give rise to epileptic encephalopathies and unspecific mental retardation, sometimes associated to signs of cerebellar dysfunction, convulsions and alterations in neuroimaging studies. Overall incidence of these diseases is low but they are unquestionably under-diagnosed, since they cannot be detected by conventional studies in plasma and urine, and require extraction and directed analysis of cerebrospinal fluid (CSF) for their detection. Additionally, the CSF study must be carried out in specific standardised conditions. Segawa's disease, or dopa-responsive dystonia, responds extremely well to therapy, whereas the other entities respond in varying ways to the different therapeutic alternatives. CONCLUSIONS: It is important for the paediatrician to know about these entities as a group of treatable neurometabolic diseases. Moreover, their detection would allow prenatal diagnosis in the vast majority of cases.
Asunto(s)
Errores Innatos del Metabolismo , Enfermedades del Sistema Nervioso/genética , Neurotransmisores/metabolismo , Adolescente , Edad de Inicio , Niño , Trastornos de la Conducta Infantil/genética , Preescolar , Epilepsia/genética , Femenino , Humanos , Lactante , Recién Nacido , Discapacidad Intelectual/genética , Masculino , Errores Innatos del Metabolismo/líquido cefalorraquídeo , Errores Innatos del Metabolismo/diagnóstico , Errores Innatos del Metabolismo/epidemiología , Errores Innatos del Metabolismo/genética , Errores Innatos del Metabolismo/metabolismo , Errores Innatos del Metabolismo/terapia , Proteínas del Tejido Nervioso/deficiencia , Proteínas del Tejido Nervioso/genética , Enfermedades del Sistema Nervioso/líquido cefalorraquídeo , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/epidemiología , Enfermedades del Sistema Nervioso/metabolismo , Enfermedades del Sistema Nervioso/terapia , Neurología , PediatríaRESUMEN
Tetrahydrobiopterin (BH4) supplementation has been applied in PKU treatment, resulting in successful control of blood phenylalanine (Phe) concentrations. We evaluated serotonin status in PKU patients under classical dietary treatment (n = 40) and in a group of 11 PKU patients under BH4 treatment, both during a 6-month period. Platelet serotonin values were significantly lower in PKU patients under dietary treatment when compared with controls. A negative correlation was observed between plasma Phe and platelet serotonin concentrations (r = -0.367, p = 0.017) in PKU patients. Platelet serotonin concentration increased significantly after both 1 and 6 months of BH4 therapy when compared with baseline conditions (Wilcoxon test: p = 0.013 and p = 0.021, respectively), while no differences were observed when comparing plasma Phe concentrations at the different points. Our results indicate that PKU patients under classical treatment have decreased platelet serotonin concentrations, probably owing to continued high Phe values, while BH4 supplementation restored platelet serotonin values.
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Biopterinas/análogos & derivados , Dieta , Fenilcetonurias/dietoterapia , Fenilcetonurias/genética , Serotonina/sangre , Adolescente , Adulto , Biopterinas/uso terapéutico , Plaquetas/metabolismo , Niño , Preescolar , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Lactante , Masculino , Fenilalanina/química , Fenilalanina Hidroxilasa/metabolismo , Serotonina/metabolismo , Triptófano/química , Triptófano/metabolismo , Triptófano Hidroxilasa/metabolismoRESUMEN
INTRODUCTION: Progressive subacute encephalopathy due to human immunodeficiency virus (PSE-HIV) is an important cause of morbidity and mortality in perinatal HIV infection. Although current combined antiretroviral therapies do manage to check its progression, they often give rise to severe motor sequelae that are similar to the spastic infantile cerebral palsy resulting from other aetiologies. We present the case reports of four preschool age children suffering from this pathology who have benefited from long term treatment with botulinum toxin type A (BTA). CASE REPORTS: Four patients suffering from early onset PSE HIV, who responded well to combined antiviral therapies, and who had severe motor sequelae (two cases of tetraparesis and two spastic dysplegias), with no cognitive disorders. The multidisciplinary treatment of their motor disorder included six monthly sessions of muscular injections of BTA in the usual doses, with good results from the functional point of view and with no significant side effects. DISCUSSION: PSE-HIV is defined by one of the following criteria: acquired microcephalus, retarded neurological development or symmetrical motor involvement. It constitutes one of the most frequent diagnostic criteria of AIDS in patients infected by vertical transmission. An early diagnosis and treatment are fundamental for the patient's prognosis. Severe motor sequelae in the form of spastic infantile cerebral palsy are frequent. In our experience treatment of the spasticity associated to this entity with BTA has proved to be useful and safe, with a clear improvement in gait functionality.