RESUMEN
An adopted 3(1/2)-year-old girl with no prior medical problems died after a routine dental procedure. More than 2 years later, acylcarnitine analysis of dried blood found on her bedding revealed she had very long chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency. Perioperative oral fasting, without intravenous administration of glucose, may be detrimental to children with certain metabolic and endocrine disorders. Newborn screening by tandem mass spectrometry will detect disorders of fatty acid oxidation such as VLCAD and allow early and preventive treatment.
Asunto(s)
Sedación Consciente/efectos adversos , Ayuno/efectos adversos , Ácido Graso Desaturasas/deficiencia , Acil-CoA Deshidrogenasa de Cadena Larga , Resultado Fatal , Femenino , Humanos , Recién NacidoRESUMEN
A case report of 3-ketothiolase deficiency due to a defect of mitochondrial acetoacetyl-CoA thiolase protein in a Brazilian boy and its biochemical investigation is presented. The child had moderate generalized hypotonia, EEG alterations and crises of metabolic acidosis following infections. Hypotonia and EEG abnormalities disappeared with a low protein diet, and physical and mental development are normal. Urinary organic acid excretion was typical of 3-ketothiolase deficiency, showing consistently high levels of 2-methyl-3-hydroxybutyric acid and tiglylglycine. Activation of acetoacetyl-CoA thiolase activity by potassium (K) ion in cultured fibroblasts was not observed, demonstrating the lack of activity of mitochondrial acetoacetyl-CoA thiolase. In addition, the signal for the mitochondrial acetoacetyl-CoA thiolase protein was undetectable in the immunoblot analysis. In the pulse-chase experiments, the signal for mitochondrial acetoacetyl-CoA thiolase was detected after a 1-h pulse but not after a 24-h chase. These results indicate that the deficiency was caused by an unstable mitochondrial acetoacetyl-CoA thiolase protein.
Asunto(s)
Acetil-CoA C-Acetiltransferasa/deficiencia , Mitocondrias/enzimología , Acetil-CoA C-Acetiltransferasa/genética , Brasil , Preescolar , Activación Enzimática , Humanos , Masculino , PotasioAsunto(s)
Ligasas de Carbono-Carbono , Ligasas/deficiencia , Biotina/uso terapéutico , Carnitina/deficiencia , Preescolar , Femenino , Humanos , MasculinoRESUMEN
Biotin deficiency associated with total parenteral nutrition is an emerging clinical problem; criteria for diagnosis and dosage for treatment are unclear. We have diagnosed and successfully treated biotin deficiency in three patients. Each patient had alopecia totalis, hypotonia, and developmental delay. Two developed the characteristic scaly periorificial dermatitis; one had only an intermittent scaly rash on the cheeks and occipital scalp. Zinc and essential fatty acid supplements were adequate; serum zinc levels and triene/tetraene ratios confirmed sufficiency of these nutrients. None of the patients received biotin prior to diagnosis, and each had decreased excretion of urinary biotin and increased urinary excretion of organic acids diagnostic of deficiency of two biotin-dependent enzymes (methylcrotonyl-coenzyme A carboxylase and priopionyl-coenzyme A carboxylase). Only one patient had a plasma biotin concentration below the normal range (Ochromonicas danica assay). The rash, alopecia, and neurologic findings responded dramatically to biotin therapy (100 micrograms/day in all patients; an initial larger dose of 1 mg/day for 1 week plus 10 mg/day for 7 weeks in one patient), and did not recur. However, abnormal organic acid excretion persisted in one patient who did not receive the larger dose. We conclude that plasma biotin concentration does not reflect biotin status in all cases and speculate that the biotin supplement currently recommended for pediatric patients (20 micrograms/day) may not be adequate therapy for biotin deficiency and might not even be adequate to maintain normal biotin status during TPN.
Asunto(s)
Biotina/deficiencia , Ácido Láctico/análogos & derivados , Nutrición Parenteral/efectos adversos , Alopecia/etiología , Biotina/orina , Citratos/orina , Diagnóstico Diferencial , Eritema/etiología , Ácidos Grasos Esenciales/deficiencia , Femenino , Glicina/análogos & derivados , Glicina/orina , Humanos , Lactante , Isomerismo , Lactatos/orina , Masculino , Enfermedades del Sistema Nervioso/etiología , Valeratos/orina , Zinc/deficienciaAsunto(s)
Errores Innatos del Metabolismo de los Aminoácidos , Propionatos/sangre , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/terapia , Biotina/uso terapéutico , Carboxiliasas/metabolismo , Diagnóstico Diferencial , Femenino , Tamización de Portadores Genéticos , Humanos , Recién Nacido , Metilmalonil-CoA Descarboxilasa , Embarazo , Diagnóstico Prenatal , Pronóstico , Propionatos/metabolismo , Desequilibrio Hidroelectrolítico/etiología , Desequilibrio Hidroelectrolítico/terapiaAsunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/tratamiento farmacológico , Biotina/uso terapéutico , Carboxiliasas/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/genética , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Biotina/análisis , Carboxiliasas/análisis , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , MasculinoAsunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/complicaciones , Enfermedades del Sistema Nervioso Central/etiología , Glicina/metabolismo , Enfermedades del Sistema Nervioso Central/patología , Corteza Cerebral/patología , Femenino , Humanos , Lactante , Recién Nacido , Degeneración Nerviosa , Serina/sangre , Valina/sangreRESUMEN
Two infants have been studied with glutaric aciduria Type II. The clinical presentation was of an overwhelming illness very early in life; both infants died in the neonatal period. One had dysmorphic features. An acrid odor may be a clue to the diagnosis. Neonatal acidosis, hypoglycemia, and hyperammonemia are characteristic. Organic acid analysis revealed massive lactic aciduria and glutaric aciduria. A variety of other dicarboxylic acids and hydroxy acids and amino acids were found in elevated amounts in body fluids, along with elevated concentrations of butyric, isobutyric, 2-methylbutyric, and isovaleric acids. The pattern of metabolites accumulated is consistent with deficient activity of a number of acyl-CoA dehydrogenases.
Asunto(s)
Glutaratos/orina , Errores Innatos del Metabolismo/orina , Aminoácidos/sangre , Ácidos Dicarboxílicos/sangre , Ácidos Dicarboxílicos/orina , Genes Recesivos , Humanos , Hidroxiácidos/sangre , Hidroxiácidos/orina , Recién Nacido , Masculino , Errores Innatos del Metabolismo/sangre , Errores Innatos del Metabolismo/genética , Aminoacidurias Renales/diagnósticoRESUMEN
A variant form of hypoxanthine-guanine phosphoribosyl transferase has been found in a neurologically normal pediatric patient who presented with hematuria an episodes of oliguria and azotemia. The level of erythrocyte enzyme activity was 3% of normal. Electrophoretic mobility was more rapid than normal. The Km for hypoxanthine was approximately ten times normal. Immunochemical analysis indicated that the variant enzyme cross reacted with antibody to normal HPRT. A system is described for the systematic characterization of a variant HPRT.
Asunto(s)
Hipoxantina Fosforribosiltransferasa/deficiencia , Ácido Úrico/sangre , Anticuerpos/análisis , Preescolar , Eritrocitos/enzimología , Femenino , Hematuria/enzimología , Hematuria/etiología , Humanos , Hipoxantina Fosforribosiltransferasa/sangre , Hipoxantina Fosforribosiltransferasa/inmunología , Oliguria/enzimología , Oliguria/etiología , Embarazo , Uremia/enzimología , Uremia/etiologíaAsunto(s)
Amoníaco/sangre , Carboxiliasas/deficiencia , Glicina/metabolismo , Propionatos/sangre , Humanos , Recién Nacido , Hígado/metabolismo , MasculinoRESUMEN
A premature infant presented with elevated concentrations of tyrosine in blood and urine, evidence of hepatocellular damage, demineralization of the bones, and a renal Fanconi syndrome. This is the clinical picture found in hereditary tyrosinemia. The infant also had a perinatal infection with cytomegalovirus.
Asunto(s)
Infecciones por Citomegalovirus/complicaciones , Enfermedades del Recién Nacido/complicaciones , Tirosina/sangre , Diagnóstico Diferencial , Humanos , Recién Nacido , Lactatos/orina , Hígado/metabolismo , Masculino , Metionina/sangre , Fenoles/orina , Tirosina/metabolismoRESUMEN
Propionyl CoA carboxylase deficiency was found in a 7-month-old boy who presented with attacks of vomiting, anorexia, weight loss, weakness, and hypotonia. He failed to thrive and had generalized seizures. He had propionic acidemia and hyperglycinemia; these are the manifestations of the ketotic hyperglycinemia syndrome. However, ketonuria was not a consistent part of his clinical picture, and he had at least two episodes of acute overwhelming illness, the latter one fatal, in which ketones were never found in the urine. Large amounts of pyrrolidone carboxylic acid were found in body fluids.