RESUMEN
Succinic semialdehyde dehydrogenase deficiency (SSADHD) is an inherited metabolic disorder of γ-aminobutyrate (GABA) catabolism. Cerebral waste clearance along glymphatic perivascular spaces depends on aquaporin 4 (AQP4) water channels, the function of which was shown to be influenced by GABA. Sleep disturbances are associated independently with SSADHD and glymphatic dysfunction. This study aimed to determine whether indices of the hyperGABAergic state characteristic of SSADHD coincide with glymphatic dysfunction and sleep disturbances and to explicate the modulatory effect that GABA may have on the glymphatic system. The study included 42 individuals (21 with SSADHD; 21 healthy controls) who underwent brain MRIs and magnetic resonance spectroscopy (MRS) for assessment of glymphatic dysfunction and cortical GABA, plasma GABA measurements, and circadian clock gene expression. The SSADHD subjects responded to an additional Children's Sleep Habits Questionnaire (CSHQ). Compared with the control group, SSADHD subjects did not differ in sex and age but had a higher severity of enlarged perivascular spaces in the centrum semiovale (p < 0.001), basal ganglia (p = 0.01), and midbrain (p = 0.001), as well as a higher MRS-derived GABA/NAA peak (p < 0.001). Within the SSADHD group, the severity of glymphatic dysfunction was specific for a lower MRS-derived GABA/NAA (p = 0.04) and lower plasma GABA (p = 0.004). Additionally, the degree of their glymphatic dysfunction correlated with the CSHQ-estimated sleep disturbances scores (R = 5.18, p = 0.03). In the control group, EPVS burden did not correlate with age or cerebral and plasma GABA values. The modulatory effect that GABA may exert on the glymphatic system has therapeutic implications for sleep-related disorders and neurodegenerative conditions associated with glymphatic dysfunction.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos , Sistema Glinfático , Imagen por Resonancia Magnética , Trastornos del Sueño-Vigilia , Succionato-Semialdehído Deshidrogenasa , Ácido gamma-Aminobutírico , Humanos , Masculino , Femenino , Ácido gamma-Aminobutírico/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/fisiopatología , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Trastornos del Sueño-Vigilia/fisiopatología , Sistema Glinfático/fisiopatología , Niño , Succionato-Semialdehído Deshidrogenasa/deficiencia , Espectroscopía de Resonancia Magnética , Adolescente , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Encéfalo/metabolismo , Acuaporina 4 , Laringoestenosis/fisiopatología , Preescolar , Discapacidades del DesarrolloRESUMEN
We report the case of a Syrian female refugee with late diagnosis of glutaric aciduria type 1 characterised by massive axial hypotonia and quadriplegia who only started adequate diet upon arrival in Switzerland at the age of 4 years, after a strenuous migration journey. Soon after arrival, she died from an unexpected severe upper cervical myelopathy, heralded by acute respiratory distress after a viral infection. This was likely due to repeated strains on her hypotonic neck and precipitated by an orthotopic os odontoideum who led to atlanto-axial subluxation. This case reminds us not to omit handling patients with insufficient postural control and hypotonia with great care to avoid progressive cervical myelopathy.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos , Encefalopatías Metabólicas , Glutaril-CoA Deshidrogenasa , Apófisis Odontoides , Enfermedades de la Médula Espinal , Preescolar , Femenino , Humanos , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Glutaril-CoA Deshidrogenasa/deficiencia , Hipotonía MuscularRESUMEN
PURPOSE: Serine (Ser) and glycine (Gly) levels were reported to differ between patients with macular telangiectasia type 2 (MacTel) compared with healthy controls. Because they are closely related to methylation metabolism, this report investigates methylation-associated metabolite levels in patients with MacTel and retinal changes in monogenetic methylation disorders. METHODS: Prospective, monocentric study on patients with MacTel and healthy controls underwent a standardized protocol including a blood draw. Methylation-associated metabolite levels in plasma were determined using targeted quantitative metabolomics. Furthermore, patient records of cystathionine beta-synthase, methylenetetrahydrofolate reductase, and methylmalonic aciduria and homocystinuria type C protein (MMACHC) deficiency were screened for reported retinal changes. RESULTS: In total, 29 patients with MacTel and 27 healthy controls were included. Patients with MacTel showed lower plasma Ser ( P = 0.02 and P = 0.01) and Gly ( P = 0.11 and P = 0.11) levels than controls. Principal component analyses revealed that methylation-associated metabolite, especially homocysteine, contributed to a distinct clustering of patients with MacTel. No retinal changes were seen in cystathionine beta-synthase (n = 1) and methylenetetrahydrofolate reductase (n = 2) deficiency, while two patients with MMACHC (n = 4) deficiency displayed extensive macular dystrophy. CONCLUSION: Patients with MacTel show distinct clustering of methylation-associated metabolite compared with controls. Of the three homocystinurias, only MMACHC resulted in macular dystrophy, possibly due to distinct compensatory pathways.
Asunto(s)
Telangiectasia Retiniana , Humanos , Femenino , Masculino , Estudios Prospectivos , Telangiectasia Retiniana/diagnóstico , Telangiectasia Retiniana/metabolismo , Telangiectasia Retiniana/genética , Persona de Mediana Edad , Tomografía de Coherencia Óptica , Adulto , Anciano , Metilación , Errores Innatos del Metabolismo de los Aminoácidos/genética , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Angiografía con Fluoresceína/métodos , Glicina , Homocistinuria/genética , Homocistinuria/complicaciones , Homocistinuria/diagnósticoRESUMEN
BACKGROUND: Combined methylmalonic acidemia (MMA) and hyperhomocysteinemia, cobalamin C (cblC) type, also named cblC deficiency is a rare autosomal recessive genetic metabolic disease. It progressively causes neurological, hematologic, renal and other system dysfunction. The clinical manifestations are relatively different due to the onset time of disease. CASE PRESENTATION: This report describes a rare case of a 26 year old man with cblC deficiency who developed life-threatening aortic dissection and acute kidney injury (AKI) and showed neuropsychiatric symptoms with elevated serum homocysteine and methylmalonic aciduria. After emergent operation and intramuscular cobalamin supplementation therapy, the male recovered from aortic dissection, neurological disorder and AKI. Finally, two previously published compound heterozygous variants, c.482G > A (p.R161Q) and c.658_660del (p.K220del) in the MMACHC gene were detected in this patient and he was confirmed to have cblC deficiency. CONCLUSIONS: Poor cognizance of presenting symptoms and biochemical features of adult onset cblC disease may cause delayed diagnosis and management. This case is the first to depict a case of adult-onset cblC deficiency with aortic dissection. This clinical finding may contribute to the diagnosis of cblC deficiency.
Asunto(s)
Lesión Renal Aguda , Errores Innatos del Metabolismo de los Aminoácidos , Hiperhomocisteinemia , Adulto , Masculino , Humanos , Hiperhomocisteinemia/complicaciones , Hiperhomocisteinemia/diagnóstico , Hiperhomocisteinemia/genética , Vitamina B 12 , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/genética , Lesión Renal Aguda/etiología , OxidorreductasasAsunto(s)
Errores Innatos del Metabolismo de los Aminoácidos , Leucoencefalopatías , Enfermedades de la Médula Espinal , Estado Epiléptico , Humanos , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Estado Epiléptico/etiologíaRESUMEN
A distinct adipose tissue distribution pattern was observed in patients with methylmalonyl-CoA mutase deficiency, an inborn error of branched-chain amino acid (BCAA) metabolism, characterized by centripetal obesity with proximal upper and lower extremity fat deposition and paucity of visceral fat, that resembles familial multiple lipomatosis syndrome. To explore brown and white fat physiology in methylmalonic acidemia (MMA), body composition, adipokines, and inflammatory markers were assessed in 46 patients with MMA and 99 matched controls. Fibroblast growth factor 21 levels were associated with acyl-CoA accretion, aberrant methylmalonylation in adipose tissue, and an attenuated inflammatory cytokine profile. In parallel, brown and white fat were examined in a liver-specific transgenic MMA mouse model (Mmut-/- TgINS-Alb-Mmut). The MMA mice exhibited abnormal nonshivering thermogenesis with whitened brown fat and had an ineffective transcriptional response to cold stress. Treatment of the MMA mice with bezafibrates led to clinical improvement with beiging of subcutaneous fat depots, which resembled the distribution seen in the patients. These studies defined what we believe to be a novel lipodystrophy phenotype in patients with defects in the terminal steps of BCAA oxidation and demonstrated that beiging of subcutaneous adipose tissue in MMA could readily be induced with small molecules.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos , Factores de Crecimiento de Fibroblastos , Lipodistrofia , Animales , Humanos , Ratones , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/genética , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Ratones TransgénicosRESUMEN
BACKGROUND: Lysinuric protein intolerance (LPI) is a multi-organ metabolic disorder characterized by the imbalance in absorption and excretion of cationic amino acids like lysine, ornithine and arginine. Infants with LPI typically present with recurrent vomiting, poor growth, interstitial lung disease or renal impairment. The early onset of pulmonary alveolar proteinosis (PAP) has been reported to be associated with a severe form of LPI. Treatment of PAP most commonly consists of whole-lung lavage (WLL) and in autoimmune PAP, granulocyte-macrophage colony stimulating factor (GM-CSF) administration. Nevertheless, GM-CSF therapy in LPI-associated PAP has not been scientifically justified. CASE PRESENTATION: We describe the case of an 8-month-old infant presenting with respiratory failure due to LPI associated with PAP, who was twice treated with WLL; firstly, while on veno-venous ECMO assistance and then by the use of a selective bronchial blocker. After the two treatments with WLL, she was weaned from daytime respiratory support while on initially subcutaneous, then on inhaled GM-CSF therapy. CONCLUSIONS: This case supports the notion that GM-CSF therapy might be of benefit in patients with LPI-associated PAP. Further studies are needed to clarify the exact mechanism of GM-CSF in patients with LPI-associated PAP.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos , Lavado Broncoalveolar , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Proteinosis Alveolar Pulmonar , Humanos , Proteinosis Alveolar Pulmonar/terapia , Factor Estimulante de Colonias de Granulocitos y Macrófagos/uso terapéutico , Lactante , Femenino , Errores Innatos del Metabolismo de los Aminoácidos/terapia , Errores Innatos del Metabolismo de los Aminoácidos/complicacionesRESUMEN
BACKGROUND: Methylmalonic acidemia is a very rare genetic metabolic disease. Patients with isolated methylmalonic acidemia typically present with acute alterations of consciousness, failure to thrive, anorexia, vomiting, respiratory distress, and muscular hypotonia. Despite the evidence-based management, affected individuals experience significant morbidity and mortality. Hyperkalemia is one of the unusual complications of methylmalonic acidemia. CASE PRESENTATION: In this paper, we describe a 4-year-old Persian boy with methylmalonic acidemia who developed life-threatening arrhythmia following severe hyperkalemia and metabolic acidosis. Emergent management of the condition was successfully carried out, and the rhythm changed to normal sinus rhythm by effectively reducing the serum potassium level. We discuss the possible etiology of this lethal condition and describe its management on the basis of the available evidence. CONCLUSION: During metabolic decompensation in methylmalonic acidemia, frequent blood gas and electrolyte testing to prescribe and adjust therapy and annual echocardiogram and electrocardiogram screening are essential.
Asunto(s)
Acidosis , Errores Innatos del Metabolismo de los Aminoácidos , Hiperpotasemia , Masculino , Humanos , Preescolar , Hiperpotasemia/terapia , Hiperpotasemia/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/genética , Acidosis/etiología , Arritmias Cardíacas/complicacionesRESUMEN
BACKGROUND: Succinic semialdehyde dehydrogenase deficiency (SSADHD) represents a model neurometabolic disease at the fulcrum of translational research within the Boston Children's Hospital Intellectual and Developmental Disabilities Research Centers (IDDRC), including the NIH-sponsored natural history study of clinical, neurophysiological, neuroimaging, and molecular markers, patient-derived induced pluripotent stem cells (iPSC) characterization, and development of a murine model for tightly regulated, cell-specific gene therapy. METHODS: SSADHD subjects underwent clinical evaluations, neuropsychological assessments, biochemical quantification of γ-aminobutyrate (GABA) and related metabolites, electroencephalography (standard and high density), magnetoencephalography, transcranial magnetic stimulation, magnetic resonance imaging and spectroscopy, and genetic tests. This was parallel to laboratory molecular investigations of in vitro GABAergic neurons derived from induced human pluripotent stem cells (hiPSCs) of SSADHD subjects and biochemical analyses performed on a versatile murine model that uses an inducible and reversible rescue strategy allowing on-demand and cell-specific gene therapy. RESULTS: The 62 SSADHD subjects [53% females, median (IQR) age of 9.6 (5.4-14.5) years] included in the study had a reported symptom onset at ⼠6 months and were diagnosed at a median age of 4 years. Language developmental delays were more prominent than motor. Autism, epilepsy, movement disorders, sleep disturbances, and various psychiatric behaviors constituted the core of the disorder's clinical phenotype. Lower clinical severity scores, indicating worst severity, coincided with older age (R= -0.302, p = 0.03), as well as age-adjusted lower values of plasma γ-aminobutyrate (GABA) (R = 0.337, p = 0.02) and γ-hydroxybutyrate (GHB) (R = 0.360, p = 0.05). While epilepsy and psychiatric behaviors increase in severity with age, communication abilities and motor function tend to improve. iPSCs, which were differentiated into GABAergic neurons, represent the first in vitro neuronal model of SSADHD and express the neuronal marker microtubule-associated protein 2 (MAP2), as well as GABA. GABA-metabolism in induced GABAergic neurons could be reversed using CRISPR correction of the pathogenic variants or mRNA transfection and SSADHD iPSCs were associated with excessive glutamatergic activity and related synaptic excitation. CONCLUSIONS: Findings from the SSADHD Natural History Study converge with iPSC and animal model work focused on a common disorder within our IDDRC, deepening our knowledge of the pathophysiology and longitudinal clinical course of a complex neurodevelopmental disorder. This further enables the identification of biomarkers and changes throughout development that will be essential for upcoming targeted trials of enzyme replacement and gene therapy.
Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos , Discapacidades del Desarrollo , Células Madre Pluripotentes Inducidas , Succionato-Semialdehído Deshidrogenasa , Adolescente , Animales , Niño , Preescolar , Femenino , Humanos , Masculino , Ratones , Errores Innatos del Metabolismo de los Aminoácidos/terapia , Errores Innatos del Metabolismo de los Aminoácidos/fisiopatología , Errores Innatos del Metabolismo de los Aminoácidos/genética , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatología , Modelos Animales de Enfermedad , Neuronas GABAérgicas/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Trastornos del Neurodesarrollo/metabolismo , Trastornos del Neurodesarrollo/etiología , Trastornos del Neurodesarrollo/genética , Succionato-Semialdehído Deshidrogenasa/deficiencia , Succionato-Semialdehído Deshidrogenasa/metabolismo , Succionato-Semialdehído Deshidrogenasa/genéticaRESUMEN
A fenilcetonúria, doença metabólica hereditária, autossômica recessiva, é a mais frequente das aminoacidopatias. Quando não diagnosticada e tratada precocemente, causa retardo mental grave. Os programas de triagem neonatal transformaram a histó- ria natural dessa doença, possibilitando o diagnóstico neonatal e a instituição imediata do tratamento dietético. Atualmente, os pacientes com controle adequado têm vida normal. Nas últimas décadas, alterações nutricionais têm sido relacionadas ao tratamento dietético e aos seus desvios, especialmente após a primeira década de vida. Neste artigo apresenta-se o caso de um adolescente que desenvolveu anemia megaloblástica por deficiente ingestão de vitamina B12 e uma revisão da literatura sobre o tema.(AU)
Phenylketonuria, inherited metabolic disease, autosomal recessive, is the most common of aminoacidopathies. If not diagnosed and treated early, causes severe mental retardation. The newborn screening programs have transformed the natural history of this disease, allowing the neonatal diagnosis and the immediate institution of dietary treatment. Currently, patients with adequate control have normal life. In recent decades, nutritional changes have been related to dietary treatment and its deviations, especially after the first decade of life. In this article we present the case of a teenager who developed megaloblastic anemia due to poor intake of vitamin B12 and a literature review on the topic(AU)
Asunto(s)
Humanos , Masculino , Adolescente , Fenilcetonurias/dietoterapia , Deficiencia de Vitamina B 12 , Anemia Megaloblástica/complicaciones , Fenilalanina , Fenilcetonurias/complicaciones , Terapia Nutricional , Errores Innatos del Metabolismo de los Aminoácidos/complicacionesRESUMEN
OBJECTIVE: to evaluate the indexes and the main factors associated with non-adherence to medication treatment for systemic arterial hypertension between urban and rural areas. METHOD: analytical study based on an epidemiological survey with a sample of 247 hypertensive residents of rural and urban areas, with application of a socio-demographic and economic questionnaire, and treatment adherence assessment. The Pearson's Chi-square test was used and the odds ratio (OD) was calculated to analyze the factors related to non-adherence. RESULTS: the prevalence of non-adherence was 61.9% and it was higher in urban areas (63.4%). Factors significantly associated with non-adherence were: male gender (OR=1.95; 95% CI 1.08-3.50), age 20-59 years old (OR=2.51; 95% CI 1.44-4.39), low economic status (OR=1.95; 95% CI 1.09-3.47), alcohol consumption (OR=5.92, 95% CI 1.73-20.21), short time of hypertension diagnosis (OR=3.07; 95% CI 1.35-6.96) and not attending the health service for routine consultations (OR=2.45; 1.35-4.42). CONCLUSION: the socio-demographic/economic characteristics, lifestyle habits and how to relate to health services were the factors that presented association with non-adherence regardless of the place of residence. .
OBJETIVO: avaliar os índices e os principais fatores associados a não adesão ao tratamento medicamentoso da hipertensão arterial sistêmica, entre área urbana e rural. MÉTODO: estudo analítico baseado em inquérito epidemiológico, realizado com amostra de 247 hipertensos moradores das áreas rural e urbana, com aplicação de questionário sociodemográfico, econômico e avaliação da adesão. Foi utilizado o teste quiquadrado de Pearson e calculado o Odds Ratio (OD) para análise dos fatores relacionados a não adesão. RESULTADOS: a prevalência da não adesão foi de 61,9%, sendo maior na área urbana (63,4%). Os fatores que apresentaram associação estatisticamente significativa com a não adesão foram: gênero masculino (OR=1,95; IC95% 1,08-3,50), faixa etária entre 20 e 59 anos (OR=2,51; IC95% 1,44-4,39), baixa classe econômica (OR=1,95; IC95% 1,09-3,47), etilismo (OR=5,92; IC 95% 1,73-20,21), tempo curto de diagnóstico de hipertensão (OR=3,07; IC95% 1,35-6,96) e não procura pelo serviço de saúde para consultas de rotina (OR=2,45; 1,35-4,42). CONCLUSÃO: as características sociodemográficas, econômicas, hábitos de vida e o modo de relacionar-se com os serviços de saúde foram os fatores que apresentaram associação com a não adesão, independentemente do local de residência. .
OBJETIVO: evaluar los índices y los principales factores asociados a la no adhesión al tratamiento medicamentoso de la hipertensión arterial sistémica entre área urbana y rural. MÉTODO: estudio analítico basado en investigación epidemiológica desarrollada con una muestra de 247 hipertensos moradores del área rural y urbana, con aplicación de un cuestionario sociodemográfico, económico y evaluación de la adhesión. Fue utilizado la prueba chi-cuadrado de Pearson y calculado el odds ratio (OD) para análisis de los factores relacionados a la no adhesión. RESULTADOS: la prevalencia de la no adhesión correspondió a 61,9%, siendo mayor en el área urbana (63,4%). Los factores que mostraron asociación estadísticamente significativa con la no adhesión fueron: género masculino (OR=1,95; IC95% 1,08-3,50), rango de edad entre 20 a 59 años (OR=2,51; IC95% 1,44-4,39), clase económica baja (OR=1,95; IC95% 1,09-3,47), etilismo (OR=5,92; IC 95% 1,73-20,21), tiempo corto de diagnóstico de hipertensión (OR=3,07; IC95% 1,35-6,96) y no procurar el servicio de salud para consultas de rutina (OR=2,45; 1,35-4,42). CONCLUSIÓN: las características sociodemográficas/económicas, hábitos de vida y el modo de relacionar con los servicios de salud fueron los factores que mostraron asociación con la no adhesión independientemente del local de residencia. .
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Predisposición Genética a la Enfermedad/genética , Prolina Oxidasa/deficiencia , Esquizofrenia , Deficiencia de Vitamina D/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/sangre , Ayuno/sangre , Modelos Estadísticos , Mutación/genética , Prolina Oxidasa/sangre , Prolina Oxidasa/genética , Prolina/metabolismo , Factores de Riesgo , Esquizofrenia/sangre , Esquizofrenia/etiología , Esquizofrenia/genética , Vitamina D/análogos & derivados , Vitamina D/sangreRESUMEN
Neutropenia exists when the neutrophil counts is less than 1000/mm3 in infants between 2 weeks and 1 year of age and less than 1500/mm3 beyond 1 year of age (1). Severe infections occur when the absolute neutrophil count is below 500/mm3 with perirectal abscesses, pneumonia, and sepsis being common. Granulocyte Colony-Stimulating Factor (G-CSF) produces a sustained neutrophil recovery in patients with severe neutropenia, reduces the incidence and severity of infection, and improves the quality of life. Various cytopenias, including neutropenia, thrombocytopenia and pancytopenia, have been reported in association with inborn errors of branched aminoacid metabolism such as methylmalonic, propionic and isovaleric acidemia. We report an infant with methylmalonic acidemia who presented severe neutropenia
Asunto(s)
Humanos , Masculino , Recién Nacido , Lactante , Ácido Metilmalónico/sangre , Acidosis/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Neutropenia/etiología , Acidosis/sangre , Acidosis/terapia , Errores Innatos del Metabolismo de los Aminoácidos/sangre , Errores Innatos del Metabolismo de los Aminoácidos/terapia , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Recien Nacido Prematuro , Neutropenia/sangre , Resultado del TratamientoRESUMEN
A hiperglicemia näo-cetótica é uma doença genética, de herança autossômica recessiva, que causa distúrbios graves em recém-nascidos, podem levar à morte. Níveis aumentados de glicina no cérebro produzem lesäo neurológica irreversível. O diagnóstico clínico é confirmado por cromatografia líquida (HPLC), comparando-se os níveis de glicina em plasma e líquido cefalorraquidiano - uma relaçäo LCR/plasma maior do que 0,09 fecha o diagnóstico. O presente estudo relata dois casos de hiperglicemia neonatal com quadro clínico e evoluçäo neurológica semelhantes. Nos dois casos, os sintomas começaram nas primeiras 48 horas de vida, e näo havia antecedentes familiares, pré-natais ou perinatais. Os dois recém-nascidos apresentaram boas condiçöes ao nascimento. Além disso, em ambos os casos, o daignóstico laboratorial (HPLC) foi bastante tardio: as amostras de sangue total e liquor foram colhidas 55§ e no 17§ dia, respectivamente. As concentraçöes de glicina em LCR e plasma, e a relaçäo LCR/plasma, foram (em mg/dl), para as crianças número 1 e número 2, repectivamente: 2,8 e 3,3 (R=0,85); 2,4 e 8 (r=0,3). Muito embora os recém-nascidos tenham permanecido em unidade de terapia intensiva e suporte ventilatório e tenham sido medicados com benzoato de sódio e diazepam, o diagnóstico tardio da hiperglicinemia acarretou lesöes neurológicas graves e irreversíveis nas duas crianças. No entanto, a importância do diagnóstico laboratorial para o aconselhamento genético dos dois casais é inquestionável
Asunto(s)
Humanos , Recién Nacido , Convulsiones/etiología , Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Glicina/metabolismo , Discapacidad Intelectual/etiología , Cromatografía Liquida , Glicina/sangre , Glicina/líquido cefalorraquídeo , Recién NacidoRESUMEN
En el presente trabajo de investigación se determinan las concentraciones del amonio plasmático, mediante la espectrofotometría cuantitativa ultravioleta de la Sigma Technical Co. en 300 neonatos de distintos pesos y edades gestacionales al nacer, manejados diagnóstica y terapeúticamente por presentar estados críticos y patológicos, atendidos en salas de parto y de "alto riesgo" en el servicio de Neonatología de la Maternidad Dr. Armando Castillo Plaza. Se distribuyeron en 5 categorías con dos grupos en cada una, en base al tipo de neonato (pretérmino o a término), Categoría A: 75 neonatos con hipoxia fetoneonatal; registraron cifras de amonio plasmático (mcg/ml) (0-6; 0-24; 24-72 horas de vida) A1: a término X 3,690 - X 2,480 - X 1,940. A2: pretérmino X 3,480 - X 2,360 - X 1,850. Categoría B: 50 neonatos con dificultad respiratoria aguda registraron cifras de amonio plasmático (mcg/ml) (0-6; 6-24; 24-72 horas de vida); B1: a término X 2,670 - X 1,920 - X 1,340. B2: pretérmino X 3,502 - X 2,320 - X 1,640. Categoría C: 50 neonatos con sepsis registraron cifras de amonio plasmático (mcg/ml) (0-72; 72-120; 120-180 horas de vida); C1: a termino X 2,270 - X 1, 690 - X 1,250. C2: pretérmino X 2,900 - X 2,320 X 1,500. Categoría D: 50 neonatos nacidos policitémicos con hiperviscocidad sanguínea registraron cifras de amonio plasmático (mcg/ml) (0-6; 6-24; 24-72 horas de vida); D1: a término X 2,150 - X 1,880 - X 1,290. D2: pretérmino X 2,320 - X 1,998 - X 1,400. Categoría E: 75 neonatos con ictericia marcada registraron cifras de amonio plasmático (mcg/ml) (0-24; 24-48; 48-72 horas de vida)..