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1.
Orphanet J Rare Dis ; 18(1): 215, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-37496092

RESUMEN

BACKGROUND: Glutaric acidemia type 1 (GA1) is a rare autosomal recessive inherited metabolic disorder caused by variants in the gene encoding the enzyme glutaryl-CoA dehydrogenase (GCDH). The estimated prevalence of GA1 and the mutational spectrum of the GCDH gene vary widely according to race and region. The aim of this study was to assess the acylcarnitine profiles and genetic characteristics of patients with GA1 in Fujian Province, southeastern China. RESULTS: From January 2014 to December 2022, a total of 1,151,069 newborns (631,016 males and 520,053 females) were screened using MS/MS in six newborn screening (NBS) centers in Fujian Province and recruited for this study. Through NBS, 18 newborns (13 females and 5 males) were diagnosed with GA1. Thus, the estimated incidence of GA1 was 1 in 63,948 newborns in Fujian province. In addition, 17 patients with GA1 were recruited after clinical diagnosis. All but one patient with GA1 had a remarkable increase in glutarylcarnitine (C5DC) concentrations. The results of urinary organic acid analyses in 33 patients showed that the concentration of glutaric acid (GA) increased in all patients. The levels of C5DC and GA in patients identified via NBS were higher than those in patients identified via clinical diagnosis (P < 0.05). A total of 71 variants of 70 alleles were detected in patients with GA1, with 19 different pathogenic variants identified. The three most prevalent variants represented 73.23% of the total and were c.1244-2 A > C, p.(?) (63.38%), c.1261G > A, p.Ala421Thr (5.63%), and c.406G > T, p.Gly136Cys (4.22%). The most abundant genotype observed was c.[1244-2 A > C]; [1244-2 A > C] (18/35, 52.43%) and its phenotype corresponded to high excretors (HE, GA > 100 mmol/mol Cr). CONCLUSIONS: In conclusion, we investigated the biochemical and molecular features of 35 unrelated patients with GA1. C5DC concentrations in dried blood spots and urinary GA are effective indicators for a GA1 diagnosis. Our study also identified a GCDH variant spectrum in patients with GA1 from Fujian Province, southeastern China. Correlation analysis between genotypes and phenotypes provides preliminary and valuable information for genetic counseling and management.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos , Encefalopatías Metabólicas , Femenino , Humanos , Masculino , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/epidemiología , Errores Innatos del Metabolismo de los Aminoácidos/genética , Encefalopatías Metabólicas/epidemiología , Encefalopatías Metabólicas/genética , China/epidemiología , Pueblos del Este de Asia , Glutaril-CoA Deshidrogenasa/genética , Espectrometría de Masas en Tándem/métodos , Recién Nacido
2.
Pediatr Neurol ; 119: 34-39, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33845444

RESUMEN

BACKGROUND: TANGO2-related metabolic encephalopathy and arrhythmias (TRMEA) is a rare, phenotypically heterogeneous, neurological disease affecting children. METHODS: We conducted a chart review of five children with molecularly confirmed TRMEA diagnosed at our institution and compiled pathogenic variant frequency and symptom prevalence from cases previously reported in the literature. RESULTS: Including those patients in our case series, 76 patients with TRMEA have been described. Developmental delay (93%) and/or regression (71%), spasticity (78%), and seizures (57%) are common in TRMEA and frequently precede life-threatening symptoms such as metabolic decompensation with lactic acidosis (83%), cardiomyopathy (38%), and cardiac arrhythmias (68%). Deletion of exons 3 to 9 is the most common pathogenic variant (39% of alleles). The majority of reported intragenic variants (17 of 27) result in disruption of the reading frame, and no clear genotype-phenotype correlations could be identified for those variants wherein the reading frame is maintained, highlighting instead the variable expressivity of the disease. CONCLUSIONS: Patients with TRMEA frequently experience life-threatening complications that are preceded by common neurological symptoms underscoring the need for pediatric neurologists to be familiar with this condition. Additional work pertaining to disease pathophysiology and potential therapeutics is needed.


Asunto(s)
Arritmias Cardíacas , Encefalopatías Metabólicas , Estudios de Asociación Genética , Adolescente , Arritmias Cardíacas/epidemiología , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatología , Ataxia/epidemiología , Encefalopatías Metabólicas/epidemiología , Encefalopatías Metabólicas/genética , Encefalopatías Metabólicas/fisiopatología , Niño , Preescolar , Estudios de Cohortes , Discapacidades del Desarrollo/epidemiología , Femenino , Humanos , Lactante , Masculino , Prevalencia , Rabdomiólisis/epidemiología , Síndrome
3.
Mol Genet Metab ; 131(3): 325-340, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33069577

RESUMEN

Glutaric acidemia type 1 (GA1) is a disorder of cerebral organic acid metabolism resulting from biallelic mutations of GCDH. Without treatment, GA1 causes striatal degeneration in >80% of affected children before two years of age. We analyzed clinical, biochemical, and developmental outcomes for 168 genotypically diverse GA1 patients managed at a single center over 31 years, here separated into three treatment cohorts: children in Cohort I (n = 60; DOB 2006-2019) were identified by newborn screening (NBS) and treated prospectively using a standardized protocol that included a lysine-free, arginine-enriched metabolic formula, enteral l-carnitine (100 mg/kg•day), and emergency intravenous (IV) infusions of dextrose, saline, and l-carnitine during illnesses; children in Cohort II (n = 57; DOB 1989-2018) were identified by NBS and treated with natural protein restriction (1.0-1.3 g/kg•day) and emergency IV infusions; children in Cohort III (n = 51; DOB 1973-2016) did not receive NBS or special diet. The incidence of striatal degeneration in Cohorts I, II, and III was 7%, 47%, and 90%, respectively (p < .0001). No neurologic injuries occurred after 19 months of age. Among uninjured children followed prospectively from birth (Cohort I), measures of growth, nutritional sufficiency, motor development, and cognitive function were normal. Adherence to metabolic formula and l-carnitine supplementation in Cohort I declined to 12% and 32%, respectively, by age 7 years. Cessation of strict dietary therapy altered plasma amino acid and carnitine concentrations but resulted in no serious adverse outcomes. In conclusion, neonatal diagnosis of GA1 coupled to management with lysine-free, arginine-enriched metabolic formula and emergency IV infusions during the first two years of life is safe and effective, preventing more than 90% of striatal injuries while supporting normal growth and psychomotor development. The need for dietary interventions and emergency IV therapies beyond early childhood is uncertain.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/genética , Encefalopatías Metabólicas/genética , Encéfalo/metabolismo , Cuerpo Estriado/metabolismo , Glutaril-CoA Deshidrogenasa/deficiencia , Glutaril-CoA Deshidrogenasa/genética , Errores Innatos del Metabolismo de los Aminoácidos/dietoterapia , Errores Innatos del Metabolismo de los Aminoácidos/epidemiología , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Encéfalo/patología , Encefalopatías Metabólicas/dietoterapia , Encefalopatías Metabólicas/epidemiología , Encefalopatías Metabólicas/metabolismo , Carnitina/metabolismo , Niño , Preescolar , Cuerpo Estriado/patología , Dieta , Femenino , Glutaril-CoA Deshidrogenasa/metabolismo , Humanos , Lactante , Recién Nacido , Lisina/metabolismo , Masculino
4.
Saudi Med J ; 41(7): 703-708, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32601637

RESUMEN

OBJECTIVES: To determine the incidence of newborn screening (NBS) disorders and to study the key performance indicators of the program. METHODS: This retrospective single-center study enrolled all infants who underwent NBS from January 2012 to December 2017 at Prince Sultan Military Medical City, Riyadh, Saudi Arabia. We screened 17 NBS disorders. Blood samples were collected 24 hours after birth. If the initial result was positive, a second sample was collected. True positive cases were immediately referred for medical management. Data were extracted from laboratory computerized and non-computerized records using case report forms. RESULTS: During the study period, 56632 infants underwent NBS with a coverage rate of 100%. Thirty-eight cases were confirmed. The incidence of congenital hypothyroidism was 1:3775. The positive predictive value for the detection of congenital hypothyroidism was 11.8%. Propionic aciduria was the most common metabolic disorder, with an incidence of 1:14158. Very long-chain acyl CoA dehydrogenase deficiency and glutaric aciduria type 1 had an incidence of 1:18877 each. Phenylketonuria, biotinidase deficiency, maple syrup urine disease, and citrullinemia had an incidence of 1:28316 each. However, galactosemia and 3-methyl crotonyl carboxylase deficiency had the lowest incidence of 1:56632. CONCLUSION: The NBS coverage rate at our facility was 100%. Congenital hypothyroidism was the most frequently detected disorder with an incidence that matches worldwide figures. The incidence of other inherited disorders was consistent with regional figures.


Asunto(s)
Enfermedades del Recién Nacido/diagnóstico , Enfermedades del Recién Nacido/epidemiología , Tamizaje Neonatal , Acil-CoA Deshidrogenasa de Cadena Larga/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/epidemiología , Biomarcadores/sangre , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas/epidemiología , Síndromes Congénitos de Insuficiencia de la Médula Ósea/diagnóstico , Síndromes Congénitos de Insuficiencia de la Médula Ósea/epidemiología , Glutaril-CoA Deshidrogenasa/deficiencia , Humanos , Hipotiroidismo/diagnóstico , Hipotiroidismo/epidemiología , Incidencia , Recién Nacido , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/epidemiología , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/epidemiología , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/epidemiología , Valor Predictivo de las Pruebas , Acidemia Propiónica/diagnóstico , Acidemia Propiónica/epidemiología , Estudios Retrospectivos , Arabia Saudita/epidemiología , Factores de Tiempo
5.
Metab Brain Dis ; 35(6): 1009-1016, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32240488

RESUMEN

Glutaric aciduria type 1 (GA1, deficiency of glutaryl CoA dehydrogenase, glutaric acidemia type 1) (ICD-10 code: E72.3; MIM 231670) is an autosomal recessive disease caused by mutations in the gene encoding the enzyme glutaryl CoA dehydrogenase (GCDH). Herein, we present the biochemical and molecular genetic characteristics of 51 patients diagnosed with GA1 from 49 unrelated families in Russia. We identified a total of 21 variants, 9 of which were novel: c.127 + 1G > T, с.471_473delCGA, c.161 T > C (p.Leu54Pro), c.531C > A (р.Phe177Leu), c.647C > T (p.Ser216Leu), c.705G > A (р.Gly235Asp), c.898 G > A (р.Gly300Ser), c.1205G > C (р.Arg402Pro), c.1178G > A (р.Gly393Glu). The most commonly detected missense variants were c.1204C > T (p.Arg402Trp) and с.1262C > T (р.Ala421Val), which were identified in 56.38% and 11.7% of mutated alleles. A heterozygous microdeletion of the short arm (p) of chromosome 19 from position 12,994,984-13,003,217 (8233 b.p.) and from position 12,991,506-13,003,217 (11,711 b.p.) were detected in two patients. Genes located in the area of imbalance were KLF1, DNASE2, and GCDH. Patients presented typical GA1 biochemical changes in the biological fluids, except one patient with the homozygous mutation p.Val400Met. No correlation was found between the GCDH genotype and glutaric acid (GA) concentration in the cohort of our patients.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/epidemiología , Errores Innatos del Metabolismo de los Aminoácidos/genética , Encefalopatías Metabólicas/epidemiología , Encefalopatías Metabólicas/genética , Glutaril-CoA Deshidrogenasa/química , Glutaril-CoA Deshidrogenasa/deficiencia , Glutaril-CoA Deshidrogenasa/genética , Mutación Missense/genética , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Encefalopatías Metabólicas/diagnóstico , Preescolar , Femenino , Humanos , Lactante , Masculino , Estructura Secundaria de Proteína , Federación de Rusia/epidemiología
6.
Rev Med Interne ; 40(2): 88-97, 2019 Feb.
Artículo en Francés | MEDLINE | ID: mdl-30638703

RESUMEN

Metabolic encephalopathies (ME) are a common cause of admission to emergency rooms, to hospitalization wards or to intensive care units. They could account for 10 to 20% of causes of comatose states in ICU and could be associated to a poor outcome especially in older patients. Nevertheless, they are often reversible and are associated with a favorable outcome when diagnosed and rapidly treated. They correspond to an altered brain functioning secondary to the deficiency of a substance that is mandatory for the normal brain functioning or to the accumulation of a substance that can be either endogenous or exogenous. It preferably occurs in co-morbid patients, complicating its diagnosis and its management. Altered brain functioning, going from mild neuropsychological impairment to coma, movement disorders especially myoclonus and the absence of any obvious differential diagnosis are highly suggestive of the diagnosis. Whereas some biological samplings and brain MRI are essential to rule out differential diagnosis, some others, such as electroencephalogram, may be able to propose important clues in favor of the diagnosis. Once simple symptomatic measures are introduced, the treatment consists mainly in the correction of the cause. Specific treatment options are only seldom available for ME; this is the case for hepatic encephalopathy and some drug-induced encephalopathies. We will successively describe in this review the main pathophysiological mechanisms, the main causes, favoring circumstances of ME, the differential diagnosis to rule out and the etiological work-up for the diagnosis. Finally, a diagnostic and therapeutic strategy for the care of patients with ME will be proposed.


Asunto(s)
Encefalopatías Metabólicas , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/fisiología , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encéfalo/fisiopatología , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas/epidemiología , Encefalopatías Metabólicas/etiología , Diagnóstico Diferencial , Técnicas de Diagnóstico Neurológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Encefalopatía Hepática/diagnóstico , Encefalopatía Hepática/epidemiología , Humanos , Síndromes de Neurotoxicidad/diagnóstico , Síndromes de Neurotoxicidad/epidemiología , Síndromes de Neurotoxicidad/etiología
7.
Brain Dev ; 39(5): 411-417, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28010956

RESUMEN

AIM: The central tegmental tract hyperintensities (CTTH) have been found in many different pediatric neurological conditions. There is only scarce data about the value of this radiological phenomenon. In this study we aimed to show the neurological conditions associated with this radiological finding. MATERIALS AND METHODS: We performed a retrospective analysis of all pediatric brain MRI's between 2013 and 2015. After finding those patients with CTTH, we evaluated them in the pediatric neurology clinic. RESULTS: There were 41 out of 1464 brain MRI's with CTTH with 2.8% prevalence. Thirty four patients (23 male, age range 3months-98months) were available for evaluation. CTTH were present in mainly younger age group. There were many different neurological conditions associated with CTTH. These included brain tumors, epilepsy, developmental delay, metabolic disorders and genetic syndromes. CONCLUSION: CTTH is found in many different pediatric neurological conditions. Further neuropathological and prospective MRI and clinical studies are needed to better understand this interesting radiological finding.


Asunto(s)
Discapacidades del Desarrollo/epidemiología , Enfermedades del Sistema Nervioso/diagnóstico por imagen , Enfermedades del Sistema Nervioso/epidemiología , Tegmento Pontino/diagnóstico por imagen , Adolescente , Encefalopatías Metabólicas/diagnóstico por imagen , Encefalopatías Metabólicas/epidemiología , Niño , Preescolar , Discapacidades del Desarrollo/diagnóstico por imagen , Epilepsia/diagnóstico por imagen , Epilepsia/epidemiología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Incidencia , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Prevalencia
8.
Horm Mol Biol Clin Investig ; 28(2): 69-83, 2016 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-27626767

RESUMEN

Reciprocal relationships between organs are essential to maintain whole body homeostasis. An exciting interplay between two apparently unrelated organs, the bone and the brain, has emerged recently. Indeed, it is now well established that the brain is a powerful regulator of skeletal homeostasis via a complex network of numerous players and pathways. In turn, bone via a bone-derived molecule, osteocalcin, appears as an important factor influencing the central nervous system by regulating brain development and several cognitive functions. In this paper we will discuss this complex and intimate relationship, as well as several pathologic conditions that may reinforce their potential interdependence.


Asunto(s)
Enfermedades Óseas Metabólicas/epidemiología , Huesos/fisiología , Encefalopatías Metabólicas/epidemiología , Encéfalo/fisiología , Comunicación Celular , Animales , Enfermedades Óseas Metabólicas/patología , Encefalopatías Metabólicas/patología , Humanos
9.
Eur J Pediatr ; 175(7): 1001-6, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27246831

RESUMEN

UNLABELLED: Patients with glutaric aciduria type 1 (GA1), a rare inherited metabolic disorder, have an increased risk for subdural hematomas (SDHs). GA1 is therefore generally included in the differential diagnosis of children presenting with SDHs. This retrospective cohort study reviews all 25 registered, in the Dutch Diagnosis Registration for Metabolic Disorders, GA1 patients in the Netherlands. This was done between May 2014 and November 2014 to determine the lifetime incidence of SDHs in this population. Seventeen patients were diagnosed either due to clinical symptoms or because of family members with GA1. One out of these 17 had a SDH. This patient showed widened Sylvian fissures on MRI, characteristic for GA1. Eight patients were diagnosed by newborn screening. Three of them had neuroimaging results, and none of them had SDHs. This study shows an overall lower incidence (4.0 %) of SDHs in patients with GA1 than reported in the literature (20-30 %). CONCLUSION: This finding, in combination with the fact that SDHs in GA1 appear to occur only in the presence of characteristic brain abnormalities on imaging, we recommend that GA1 should not routinely be a part of the differential diagnosis of children with unexplained SDHs in the absence of imaging characteristics suggestive of GA1. WHAT IS KNOWN: • Glutaric aciduria type 1 is a rare metabolic disorder predisposing children to subdural hematoma development due to brain abnormalities. • Because of these subdural hematomas, glutaric aciduria type 1 testing is part of abusive head trauma work-up. What is new: • The overall subdural hematoma incidence in glutaric aciduria type 1 patients is much lower than previously reported and only occurs in case of predisposing brain abnormalities.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/epidemiología , Encefalopatías Metabólicas/complicaciones , Encefalopatías Metabólicas/epidemiología , Glutaril-CoA Deshidrogenasa/deficiencia , Hematoma Subdural/etiología , Adolescente , Adulto , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Encefalopatías Metabólicas/diagnóstico , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Hematoma Subdural/diagnóstico por imagen , Humanos , Incidencia , Lactante , Imagen por Resonancia Magnética , Masculino , Países Bajos/epidemiología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Adulto Joven
10.
Arch Iran Med ; 17(9): 629-32, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25204480

RESUMEN

BACKGROUND: Glutaric Aciduria type 1 (GA1) is a metabolic inborn error and is characterized by increasing excursion of glutaric acid and its derivates, presented in microcephaly and dystonia. The disease is resulted from mutational inactivation in the GCDH gene encoding the glutaryl-CoA dehydrogenase. The defective enzyme causes the accumulation of an excessive level of intermediate breakdown products that leads to the brain damage. In spite of the clinical features, diagnosis of GAI has been often confusing, because of variability in the clinical manifestations of patients. Early diagnosis and treatment can though prevent irreversible disease progression and consequent brain damage; otherwise the affected individuals will die in their first decade of lives. METHODS: The GCDH gene was also analyzed to (detect or identify) disease causing mutations using gene amplification and direct sequencing in 18 patients. RESULTS: Among 18 patients, 10 patients (55.5%) were homozygous or compounded heterozygous for the recurrent mutation E181Q, three patients (16.7%) were homozygous for the known mutation R402Q and one patient (5.6%) was compound heterozygous for S255L. All three detected missense mutations are pathogenic, which cause structural changes in the binding site and tetramerization or functional deficiency. Four other individuals (22.2%) with a preliminary diagnosis of GAI were negative for any pathogenic mutations. CONCLUSION: Most GA1 affected persons in southwest Iran are with Persian ethnicity and the most common mutation in Khuzestan Province is prominent in comparison to  previous reports from Iran.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/genética , Encefalopatías Metabólicas/genética , Glutaril-CoA Deshidrogenasa/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/epidemiología , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas/epidemiología , Dominio Catalítico , Glutaril-CoA Deshidrogenasa/química , Glutaril-CoA Deshidrogenasa/genética , Heterocigoto , Homocigoto , Humanos , Irán/epidemiología , Mutación Missense/genética , Estructura Secundaria de Proteína
11.
J Inherit Metab Dis ; 37(6): 889-98, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25022222

RESUMEN

Many newborn screening programmes now use tandem mass spectrometry in order to screen for a variety of diseases. However, countries have embraced this technology with a differing pace of change and for different conditions. This has been facilitated by the ability of this diagnostic method to limit analysis to specific metabolites of interest, enabling targeted screening for particular conditions. MS/MS was introduced in 2009 in England to implement newborn bloodspot screening for medium chain acyl-CoA dehydrogenase deficiency (MCADD) raising the possibility of screening for other inherited metabolic disorders. Recently, a pilot screening programme was conducted in order to evaluate the health and economic consequences of screening for five additional inherited metabolic disorders in England. As part of this study we conducted a systematic review and meta-analysis to estimate the birth prevalence of these conditions: maple syrup urine disease, homocystinuria (pyridoxine unresponsive), glutaric aciduria type I, isovaleric acidaemia and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency including trifunctional protein deficiency. We identified a total of 99 studies that were able to provide information on the prevalence of one or more of the disorders. The vast majority of studies were of screening programmes with some reporting on clinically detected cases.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/epidemiología , Encefalopatías Metabólicas/epidemiología , Glutaril-CoA Deshidrogenasa/deficiencia , Homocistinuria/epidemiología , Isovaleril-CoA Deshidrogenasa/deficiencia , Enfermedad de la Orina de Jarabe de Arce/epidemiología , 3-Hidroxiacil-CoA Deshidrogenasas/deficiencia , Cardiomiopatías/epidemiología , Inglaterra/epidemiología , Humanos , Recién Nacido , Errores Innatos del Metabolismo Lipídico/epidemiología , Miopatías Mitocondriales/epidemiología , Proteína Trifuncional Mitocondrial/deficiencia , Tamizaje Neonatal , Enfermedades del Sistema Nervioso/epidemiología , Rabdomiólisis/epidemiología , Espectrometría de Masas en Tándem
12.
Acta Paediatr ; 103(1): e7-e10, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24117930

RESUMEN

AIM: To review the incidence of hyponatraemic encephalopathy in children treated in a tertiary care centre hospital, together with the clinical setting and clinical management of these cases. METHODS: Retrospective descriptive study by chart review of patients admitted to hospital during 2000-2010. Patients older than 1 month were included who had severe hyponatraemia (sodium concentration <125 mmol/L) on admission or during their hospital stay and co-incidental neurological symptoms. Epidemiological, clinical, laboratory and therapeutic data were collected. RESULTS: We analysed 41 cases of severe hypotonic hyponatraemia and neurological symptoms compatible with hyponatraemic encephalopathy. Boys accounted for 56.1% patients, and the median age was 1 year. Hyponatraemia was acquired in hospital by 61% of the patients, and 88% of those patients were receiving intravenous hypotonic fluids. The most frequent neurological symptom was seizures. The most common therapeutic strategy was sodium supplementation and antiepileptic drugs. Hypertonic fluids were only used in the initial treatment of 16 patients. There were two deaths related to hyponatraemic encephalopathy. CONCLUSION: Hyponatraemia should always be considered a cause of neurological symptoms in hospitalised patients. Treatment should be prompt to prevent neurological sequelae and death. Current recommendations for fluid management in hospitalised children should be reviewed.


Asunto(s)
Encefalopatías Metabólicas/etiología , Hiponatremia/complicaciones , Enfermedad Iatrogénica/epidemiología , Unidades de Cuidado Intensivo Pediátrico/estadística & datos numéricos , Encefalopatías Metabólicas/epidemiología , Encefalopatías Metabólicas/terapia , Preescolar , Resultado Fatal , Femenino , Humanos , Hiponatremia/epidemiología , Hiponatremia/terapia , Incidencia , Lactante , Masculino , Estudios Retrospectivos , España/epidemiología , Centros de Atención Terciaria/estadística & datos numéricos
13.
J Clin Endocrinol Metab ; 99(1): 291-8, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24248182

RESUMEN

CONTEXT: Hyponatremia is common after acute subarachnoid hemorrhage (SAH) but the etiology is unclear and there is a paucity of prospective data in the field. The cause of hyponatremia is variously attributed to the syndrome of inappropriate antidiuresis (SIAD), acute glucocorticoid insufficiency, and the cerebral salt wasting syndrome (CSWS). OBJECTIVE: The objective was to prospectively determine the etiology of hyponatremia after SAH using sequential clinical examination and biochemical measurement of plasma cortisol, arginine vasopressin (AVP), and brain natriuretic peptide (BNP). DESIGN: This was a prospective cohort study. SETTING: The setting was the National Neurosurgery Centre in a tertiary referral centre in Dublin, Ireland. PATIENTS: One hundred patients with acute nontraumatic aneurysmal SAH were recruited on presentation. INTERVENTIONS: Clinical examination and basic biochemical evaluation were performed daily. Plasma cortisol at 0900 hours, AVP, and BNP concentrations were measured on days 1, 2, 3, 4, 6, 8, 10, and 12 following SAH. Those with 0900 hours plasma cortisol<300 nmol/L were empirically treated with iv hydrocortisone. MAIN OUTCOME MEASURES: Plasma sodium concentration was recorded daily along with a variety of clinical and biochemical criteria. The cause of hyponatremia was determined clinically. Later measurement of plasma AVP and BNP concentrations enabled a firm biochemical diagnosis of the cause of hyponatremia to be made. RESULTS: Forty-nine of 100 developed hyponatremia<135 mmol/L, including 14/100<130 mmol/L. The cause of hyponatremia, and determined by both clinical examination and biochemical hormone measurement, was SIAD in 36/49 (71.4%), acute glucocorticoid insufficiency in 4/49 (8.2%), incorrect iv fluids in 5/49 (10.2%), and hypovolemia in 5/49 (10.2%). There were no cases of CSWS. CONCLUSIONS: The most common cause of hyponatremia after acute nontraumatic aneurysmal SAH is SIAD. Acute glucocorticoid insufficiency accounts for a small but significant number of cases. We found no cases of CSWS.


Asunto(s)
Insuficiencia Suprarrenal/complicaciones , Encefalopatías Metabólicas/complicaciones , Glucocorticoides/deficiencia , Hiponatremia/etiología , Síndrome de Secreción Inadecuada de ADH/complicaciones , Hemorragia Subaracnoidea/complicaciones , Adolescente , Insuficiencia Suprarrenal/sangre , Insuficiencia Suprarrenal/epidemiología , Hormona Adrenocorticotrópica/sangre , Adulto , Anciano , Anciano de 80 o más Años , Encefalopatías Metabólicas/sangre , Encefalopatías Metabólicas/epidemiología , Estudios de Cohortes , Femenino , Humanos , Hidrocortisona/sangre , Hiponatremia/sangre , Hiponatremia/epidemiología , Síndrome de Secreción Inadecuada de ADH/sangre , Síndrome de Secreción Inadecuada de ADH/epidemiología , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/efectos adversos , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Sodio/metabolismo , Hemorragia Subaracnoidea/sangre , Hemorragia Subaracnoidea/epidemiología , Hemorragia Subaracnoidea/cirugía , Adulto Joven
14.
Neuroradiology ; 55 Suppl 2: 47-54, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23921419

RESUMEN

INTRODUCTION: Intensive resuscitation at birth has been linked to intraventricular haemorrhage (IVH) in the preterm neonate. However, the impact of less intensive resuscitation on more subtle alterations in brain metabolic development is largely unknown. Our objective was to determine the relationship between the intensity of neonatal resuscitation following preterm birth on brain metabolic development. METHODS: One hundred thirty-three very preterm-born neonates (median gestational age [GA] 27 ± 2 weeks) underwent MR spectroscopic imaging early in life (median postmenstrual age 32 weeks) and again at term-equivalent age (median 40 weeks). Severity of white matter injury, IVH and cerebellar haemorrhage on magnetic resonance imaging were scored. Ratios of N-acetylaspartate (NAA) and lactate to choline (Cho) were calculated in eight regions of interest and were assessed in relation to intensiveness of resuscitation strategy (bag and mask, continuous positive airway pressure [CPAP], intubation, cardiopulmonary resuscitation [CPR]). RESULTS: Within the first hour of life, 14 newborns had no intervention, 3 received bag and mask, 30 had CPAP, 79 were intubated and 7 had CPR. Resuscitated infants were more likely to have IVH (p = 0.02). More intensive resuscitation was associated with decreased NAA/Cho maturation (p < 0.001, adjusting for birth GA). Metabolic development was similar in neonates requiring CPAP in comparison to those receiving no intervention. The change in lactate/Cho did not differ across resuscitation categories (p = 0.8). CONCLUSIONS: Intensity of resuscitation at birth is related to changes in metabolic brain development from early in life to term-equivalent age. Results suggest that preventing the need for intensive neonatal resuscitation may provide an opportunity to improve brain development in preterm neonates.


Asunto(s)
Encefalopatías Metabólicas/epidemiología , Encefalopatías Metabólicas/rehabilitación , Lesiones Encefálicas/epidemiología , Lesiones Encefálicas/rehabilitación , Enfermedades del Prematuro/epidemiología , Enfermedades del Prematuro/rehabilitación , Resucitación/estadística & datos numéricos , Colombia Británica/epidemiología , Causalidad , Comorbilidad , Femenino , Humanos , Recien Nacido Prematuro , Masculino , Factores de Riesgo , Resultado del Tratamiento
16.
Continuum (Minneap Minn) ; 18(3): 611-39, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22810252

RESUMEN

PURPOSE OF REVIEW: This article summarizes the most common etiologies and approaches to management of metabolic encephalopathy. RECENT FINDINGS: Metabolic encephalopathy is a frequent occurrence in the intensive care unit setting. Common etiologies include hepatic failure, renal failure, sepsis, electrolyte disarray, and Wernicke encephalopathy. Current treatment paradigms typically focus on supportive care and management of the underlying etiology. Directed therapies that target neurochemical and neurotransmitter pathways that mediate encephalopathy are not currently available and represent an important area for future research. Although commonly thought of as reversible neurologic insults, delirium and encephalopathy have been associated with increased mortality, prolonged length of stay and hospital complications, and worse long-term cognitive and functional outcomes. SUMMARY: Recognition and treatment of encephalopathy is critical to improving outcomes in critically ill patients.


Asunto(s)
Encefalopatías Metabólicas/terapia , Cuidados Críticos/métodos , Daño Encefálico Crónico/etiología , Daño Encefálico Crónico/prevención & control , Encefalopatías Metabólicas/inducido químicamente , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas/epidemiología , Encefalopatías Metabólicas/fisiopatología , Terapia Combinada , Delirio/etiología , Enfermedades del Sistema Endocrino/complicaciones , Encefalopatía Hepática/terapia , Humanos , Unidades de Cuidados Intensivos , Cuidados para Prolongación de la Vida , Desnutrición/complicaciones , Errores Innatos del Metabolismo/complicaciones , Neuroimagen , Examen Neurológico , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Renal/complicaciones , Insuficiencia Renal/terapia , Terapia de Reemplazo Renal , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Desequilibrio Hidroelectrolítico/sangre , Desequilibrio Hidroelectrolítico/complicaciones , Desequilibrio Hidroelectrolítico/terapia
17.
Neurocrit Care ; 17(1): 49-57, 2012 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22528283

RESUMEN

BACKGROUND: Optimal resuscitation after traumatic brain injury (TBI) remains uncertain. We hypothesize that cerebral metabolic crisis is frequent despite adequate resuscitation of the TBI patient and that metabolic crisis negatively influences outcome. METHODS: We assessed the effectiveness of a standardized trauma resuscitation protocol in 89 patients with moderate to severe TBI, and determined the frequency of adequate resuscitation. Prospective hourly values of heart rate, blood pressure, pulse oximetry, intracranial pressure (ICP), respiratory rate, jugular venous oximetry, and brain extracellular values of glucose, lactate, pyruvate, glycerol, and glutamate were obtained. The incidence during the initial 72 h after injury of low brain glucose <0.8 mmol/L, elevated lactate/pyruvate ratio (LPR) >25, and metabolic crisis, defined as the simultaneous occurrence of both low glucose and high LPR, were determined for the group. RESULTS: 5 patients were inadequately resuscitated and eight patients had intractable ICP. In patients with successful resuscitation and controlled ICP (n = 76), within 72 h of trauma, 76% had low glucose, 93% had elevated LPR, and 74% were in metabolic crisis. The duration of metabolic crisis was longer in those patients with unfavorable (GOSe ≤ 6) versus favorable (GOSe ≥ 7) outcome at 6 months (P = 0.011). In four multivariate models the burden of metabolic crisis was a powerful independent predictor of poor outcome. CONCLUSIONS: Metabolic crisis occurs frequently after TBI despite adequate resuscitation and controlled ICP, and is a strong independent predictor of poor outcome at 6 months.


Asunto(s)
Encefalopatías Metabólicas/epidemiología , Encefalopatías Metabólicas/metabolismo , Lesiones Encefálicas/epidemiología , Lesiones Encefálicas/metabolismo , Encéfalo/metabolismo , Reanimación Cardiopulmonar/estadística & datos numéricos , Adulto , Presión Sanguínea/fisiología , Encefalopatías Metabólicas/fisiopatología , Lesiones Encefálicas/fisiopatología , Reanimación Cardiopulmonar/normas , Enfermedad Crítica/epidemiología , Femenino , Glucosa/metabolismo , Ácido Glutámico/metabolismo , Glicerol/metabolismo , Frecuencia Cardíaca/fisiología , Humanos , Incidencia , Ácido Láctico/metabolismo , Masculino , Microdiálisis/métodos , Persona de Mediana Edad , Oximetría , Valor Predictivo de las Pruebas , Ácido Pirúvico/metabolismo
18.
Med Sci Monit ; 17(7): PH55-9, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21709643

RESUMEN

BACKGROUND: Glutaric aciduria type I (GA I; MIM 231670) is a rare autosomal recessive disorder resulting from glutaryl-CoA dehydrogenase deficiency. This article reports our experience in the diagnosis, treatment and outcome of GA I patients in Zhejiang Province, China. MATERIAL/METHODS: A total of 129,415 newborns (accounting for approximately one-tenth of the annual births in Zhejiang Province) and 9640 high-risk infants were screened for inborn errors of metabolism in the Neonatal Screening Center of Zhejiang Province during a 3-year period. Tandem mass spectrometry and gas chromatography-mass spectrometry were used for diagnosis of the patients. Dietary modification, carnitine supplementation and aggressive treatment of intercurrent illnesses were adapted for GA I patients. RESULTS: Three infants were diagnosed with GA I by high-risk screening (detection rate: 1/3,213) and 2 were diagnosed by newborn screening (incidence: 1/64,708). Four patients (3 by high-risk screening and 1 by neonatal screening) undergoing MRI examination showed remarkable changes on T2-weighted image. Four patients accepted timely treatment, and in the patient diagnosed by neonatal screening, treatment was delayed until hypotonia appeared 3 months later. Neuropsychological assessment showed mental and motor retardation in 3 patients after treatment, including the patient diagnosed by neonatal screening. CONCLUSIONS: Individualized timely treatment and close monitoring of GA I patients needs to be optimized in China. Appropriate communication with parents may help to achieve successful management of GA I patients.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/tratamiento farmacológico , Errores Innatos del Metabolismo de los Aminoácidos/epidemiología , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas/tratamiento farmacológico , Encefalopatías Metabólicas/epidemiología , Errores Innatos del Metabolismo de los Aminoácidos/genética , Encefalopatías Metabólicas/genética , Carnitina/uso terapéutico , China/epidemiología , Femenino , Cromatografía de Gases y Espectrometría de Masas , Genes Recesivos , Glutaril-CoA Deshidrogenasa/deficiencia , Glutaril-CoA Deshidrogenasa/genética , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Tamizaje Masivo , Pruebas Neuropsicológicas , Riboflavina/uso terapéutico , Espectrometría de Masas en Tándem , Resultado del Tratamiento
19.
J Neuropsychiatry Clin Neurosci ; 22(4): 370-7, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21037120

RESUMEN

The aim of this study was to investigate limbic metabolic abnormalities in remote traumatic brain injury (TBI) and their psychiatric correlates. Twenty patients and 13 age-matched comparison subjects received complete psychiatric evaluation and brain MRI and MR spectroscopy at 3 Tesla. Patients had reduced NAA to creatine ratio in the left hippocampus relative to comparison subjects (mean=1.3 [SD=0.21] compared with mean=1.55 [SD=0.21]; F=10.73, df=1, 30, p=0.003), which correlated with the Social Functioning Examination scores (r(s)=-0.502, p=0.034). Furthermore, patients with mood disorders had reduced NAA to creatine ratio in the left cingulate relative to patients without mood disorders (1.47 compared with 1.68; F=3.393, df=3, 19, p=0.044). Remote TBI displays limbic metabolic abnormalities, which correlate to social outcome and psychiatric status.


Asunto(s)
Encefalopatías Metabólicas , Lesiones Encefálicas , Sistema Límbico/metabolismo , Trastornos Mentales/epidemiología , Ajuste Social , Estadística como Asunto , Adolescente , Adulto , Anciano , Ácido Aspártico/metabolismo , Encefalopatías Metabólicas/epidemiología , Encefalopatías Metabólicas/etiología , Encefalopatías Metabólicas/patología , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/epidemiología , Lesiones Encefálicas/patología , Mapeo Encefálico , Estudios de Casos y Controles , Colina/metabolismo , Femenino , Humanos , Sistema Límbico/patología , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Adulto Joven
20.
Acta Diabetol ; 47(4): 279-93, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20798963

RESUMEN

Diabetic encephalopathies are now accepted complications of diabetes. They appear to differ in type 1 and type 2 diabetes as to underlying mechanisms and the nature of resulting cognitive deficits. The increased incidence of Alzheimer's disease in type 2 diabetes is associated with insulin resistance, hyperinsulinemia and hyperglycemia, and commonly accompanying attributes such as hypercholesterolemia, hypertension and obesity. The relevance of these disorders as to the emergence of dementia and Alzheimer's disease is discussed based on epidemiological studies. The pathobiology of accumulation of ß-amyloid and tau the hallmarks of Alzheimer's disease are discussed based on experimental data. Type 1 diabetic encephalopathy is likely to increase as a result of the global increase in the incidence of type 1 diabetes and its occurrence in increasingly younger patients. Alzheimer-like changes and dementia are not prominently increased in type 1 diabetes. Instead, the type 1 diabetic encephalopathy involves learning abilities, intelligence development and memory retrieval resulting in impaired school and professional performances. The major underlying component here appears to be insulin deficiency with downstream effects on the expression of neurotrophic factors, neurotransmitters, oxidative and apoptotic stressors resulting in defects in neuronal integrity, connectivity and loss commonly occurring in the still developing brain. Recent experimental data emphasize the role of impaired central insulin action and provide information as to potential therapies. Therefore, the underlying mechanisms resulting in diabetic encephalopathies are complex and appear to differ between the two types of diabetes. Major headway has been made in our understanding of their pathobiology; however, many questions remain to be clarified. In view of the increasing incidence of both type 1 and type 2 diabetes, intensified investigations are called for to expand our understanding of these complications and to find therapeutic means by which these disastrous consequences can be prevented and modified.


Asunto(s)
Encefalopatías Metabólicas/etiología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Amiloide/metabolismo , Animales , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas/epidemiología , Complicaciones de la Diabetes/diagnóstico , Complicaciones de la Diabetes/epidemiología , Complicaciones de la Diabetes/psicología , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/psicología , Modelos Animales de Enfermedad , Humanos , Modelos Biológicos , Proteínas tau/metabolismo
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