RESUMO
UNLABELLED: Tyrosine supplementation has not consistently been found to improve neuropsychologic function in phenylketonuria (PKU), possibly because of failure to achieve adequate levels of tyrosine in the brain. OBJECTIVES: To evaluate blood levels achieved after tyrosine supplementation in treated PKU and calculate brain influxes of tyrosine and other large neutral amino acids before and with tyrosine supplementation. STUDY DESIGN: Ten subjects with PKU receiving a phenylalanine-restricted diet were studied over 48 hours; each received tyrosine supplementation (300 mg/kg) on day 2. Plasma phenylalanine and tyrosine were measured every 2 hours, and all free amino acids were measured every 6 hours. Brain influxes of tyrosine and other large neutral amino acids were calculated. RESULTS: Plasma tyrosine levels were low normal at baseline. With supplementation there was a substantial but unsustained rise in plasma tyrosine. Calculated brain influx of tyrosine was 27% +/- 19% of normal before supplementation, increasing to 90% +/- 58% of normal with supplementation. Nevertheless, calculated influx remained less than 70% of normal at 50% of the time points. The calculated brain influxes of all other large neutral amino acids except tryptophan were 20% to 40% of normal before and with tyrosine supplementation. CONCLUSIONS: Tyrosine supplementation in the diet for PKU produces marked but nonsustained increases in plasma tyrosine levels, with calculated brain influx that often remains suboptimal. This could explain the lack of consistent neuropsychologic benefit with tyrosine supplementation.
Assuntos
Fenilcetonúrias/tratamento farmacológico , Tirosina/uso terapêutico , Adulto , Aminoácidos/metabolismo , Encéfalo/metabolismo , Criança , Feminino , Humanos , Masculino , Tirosina/sangueRESUMO
The importance of complete or almost complete intake of the recommended amount of phenylalanine-free amino acid mixture (AAM) for control of blood phenylalanine level in patients being treated for phenylketonuria (PKU) has not been universally appreciated. We observed the effect of complete intake of AAM on plasma phenylalanine levels during hospitalization in 6 patients with PKU (5 pregnant women with PKU and 1 child) who had poor metabolic control because of less than full compliance with prescribed AAM intake. Before hospitalization, all but 1 of the patients had blood phenylalanine levels above 1,000 mumol/L; in 1 patient the blood phenylalanine level was 703 mumol/L. During 9 periods of observation in the 6 patients, the levels of plasma phenylalanine decreased to the recommended range of below 360 mumol/L within 2 to 6 days of hospitalization. These experiences indicate a close relationship between compliance with prescribed AAM intake and control of blood phenylalanine level. We propose that hospitalization be considered when patients with PKU who are consuming a phenylalanine-restricted diet fail to maintain blood phenylalanine levels in the targeted range despite reported compliance with the prescribed intake of dietary phenylalanine and AAM.
Assuntos
Aminoácidos/administração & dosagem , Dieta com Restrição de Proteínas , Fenilalanina/sangue , Fenilcetonúria Materna/dietoterapia , Adulto , Aminoácidos/metabolismo , Pré-Escolar , Ingestão de Alimentos , Feminino , Humanos , Cooperação do Paciente , Fenilalanina/efeitos adversos , Fenilalanina Hidroxilase/genética , Fenilcetonúria Materna/prevenção & controle , Gravidez , Resultado da GravidezRESUMO
Hydroxyproline is a major constituent of collagen. It accumulates as the free imino acid in a rarely reported inborn error of metabolism known as hydroxyprolinemia. This metabolic disorder was initially described in association with mental retardation, but subsequent identification in clinically normal individuals has led to the supposition that it is benign. The possibility that hydroxyprolinemia might have an adverse effect on cognitive development without producing mental retardation has not been determined nor has its incidence been reported. We prospectively studied a girl with untreated hydroxyprolinemia identified by routine neonatal urine screening, the only infant found among 1 million screened, and compared her with her unaffected dizygotic twin sister. Plasma and urine hydroxyproline were increased approximately 10-fold and 100-fold, respectively, in the affected twin. Both girls have had normal growth, with the affected twin taller than her sister. On neuropsychologic testing, the affected twin was within normal limits, performing slightly better than her sister on verbal and achievement tests but less well on visual perceptual testing. It appears that hydroxyprolinemia has caused no physical or general cognitive deficits. The possibility of an effect on visual perceptual functioning, although unlikely, cannot be eliminated.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/genética , Doenças em Gêmeos , Hidroxiprolina/sangue , Erros Inatos do Metabolismo dos Aminoácidos/fisiopatologia , Erros Inatos do Metabolismo dos Aminoácidos/psicologia , Criança , Feminino , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Testes Neuropsicológicos , Estudos Prospectivos , Gêmeos Dizigóticos , Percepção VisualRESUMO
A major complication of galactosemia is cataracts. This is usually considered to be the sole ophthalmic feature of this disorder. However, we have encountered vitreous hemorrhage, a very rare ophthalmic finding, in five neonates with galactosemia and have found four probable additional cases in the literature. All of these infants had severe neonatal manifestations of galactosemia and were discovered to have vitreous hemorrhage by ophthalmologic examination initiated by the observation of clouding of the eye or on a routine basis. The infants lost most or all vision from the affected eye. Retinal abnormalities were present in the involved eyes of the five neonates of whom we have direct knowledge. Thus we believe that retinal hemorrhage is the most likely source of the vitreous hemorrhage and that the coagulopathy associated with neonatal disease in galactosemia leads to vitreous hemorrhage. Prompt recognition and therapy for the coagulopathy would likely prevent vitreous hemorrhage in galactosemia.
Assuntos
Galactosemias/complicações , Hemorragia Vítrea/etiologia , Feminino , Galactosemias/diagnóstico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/diagnóstico , Doenças do Prematuro/cirurgia , Masculino , Prognóstico , Vitrectomia , Hemorragia Vítrea/diagnóstico , Hemorragia Vítrea/cirurgiaRESUMO
Phenylketonuria (PKU) produces white matter changes identifiable by magnetic resonance imaging. These changes occur postnatally. Offspring of untreated mothers with PKU also have a brain effect, expressed as microcephaly and mental retardation. This effect occurs prenatally. To determine whether the white matter changes seen in PKU are also present in maternal PKU offspring, despite the different developmental stages of exposure to PKU, we performed brain magnetic resonance imaging studies in seven maternal PKU offspring, five from essentially untreated pregnancies and two from treated pregnancies. None had white matter changes, although the one offspring with PKU had delayed myelination. However, hypoplasia of the corpus callosum was present in three of the four offspring from untreated pregnancies and in the offspring from a maternal PKU pregnancy not treated until the third trimester. Unlike PKU, white matter changes are not a feature of the brain effect in maternal PKU. However, hypoplasia of the corpus callosum is a feature of maternal PKU and is probably a result of inhibition of corpus callosum development at 8 to 20 weeks of gestation. The hypoplastic corpus callosum could be a marker for brain effect in maternal PKU and may have implications for the cognitive deficits in these offspring.
Assuntos
Encéfalo/patologia , Deficiência Intelectual/genética , Imageamento por Ressonância Magnética , Microcefalia/genética , Mães , Fenilcetonúrias/genética , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Agenesia do Corpo Caloso , Criança , Corpo Caloso/patologia , Feminino , Seguimentos , Humanos , Lactente , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/prevenção & controle , Masculino , Microcefalia/diagnóstico , Microcefalia/prevenção & controle , Fenilalanina/administração & dosagem , Fenilcetonúrias/diagnóstico , Fenilcetonúrias/dietoterapia , GravidezRESUMO
The outcomes of mild hyperphenylalaninemia (MHP) in three children of two sisters were compared. The IQ of the child from an untreated pregnancy was 105; the developmental quotients of the two infant offspring from treated and untreated pregnancies were 122 and 114, respectively. The IQ of the sister with untreated MHP was 101; that of the sister who received dietary treatment for MHP during infancy was 90. Thus MHP and maternal MHP appear to have been clinically inconsequential in this family.
Assuntos
Inteligência , Fenilalanina/sangue , Complicações na Gravidez , Adulto , Desenvolvimento Infantil , Diabetes Gestacional/sangue , Diabetes Gestacional/tratamento farmacológico , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Inteligência/genética , Masculino , Fenilalanina/genética , Fenilcetonúrias/sangue , Fenilcetonúrias/dietoterapia , Fenilcetonúrias/genética , GravidezAssuntos
Galactosemias/sangue , Galactosemias/terapia , Uridina Difosfato Galactose/deficiência , Criança , Cromatografia Líquida de Alta Pressão , Eritrócitos/química , Galactosemias/complicações , Humanos , Espectroscopia de Ressonância Magnética , Uridina/uso terapêutico , Uridina Difosfato Galactose/sangue , Uridina Difosfato Galactose/isolamento & purificação , Uridina Difosfato Glucose/sangue , Uridina Difosfato Glucose/isolamento & purificação , Uridina Difosfato Glucose DesidrogenaseRESUMO
A 6-month-old girl was hospitalized on three occasions for irritability, vomiting, acidosis, and hypotonia. During the third hospitalization hyperglycinemia and urinary glycolic acid were detected. Ethylene glycol was discovered in the infant's blood and bottled formula. Clinicians must consider ethylene glycol intoxication as a cause of recurrent infantile metabolic acidosis.