RESUMEN
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.
Asunto(s)
Aminoácidos/administración & dosificación , Dieta con Restricción de Proteínas , Fenilalanina/sangre , Fenilcetonuria Materna/dietoterapia , Adulto , Aminoácidos/metabolismo , Preescolar , Ingestión de Alimentos , Femenino , Humanos , Cooperación del Paciente , Fenilalanina/efectos adversos , Fenilalanina Hidroxilasa/genética , Fenilcetonuria Materna/prevención & control , Embarazo , Resultado del EmbarazoRESUMEN
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.
Asunto(s)
Inteligencia , Fenilalanina/sangre , Complicaciones del Embarazo , Adulto , Desarrollo Infantil , Diabetes Gestacional/sangre , Diabetes Gestacional/tratamiento farmacológico , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Inteligencia/genética , Masculino , Fenilalanina/genética , Fenilcetonurias/sangre , Fenilcetonurias/dietoterapia , Fenilcetonurias/genética , EmbarazoRESUMEN
Eight polymorphic sites for seven restriction endonucleases have been reported at the human phenylalanine hydroxylase locus. The composite profile of the presence or absence for each of the eight polymorphic sites within an allele defines the haplotype of the corresponding allele. Twelve such haplotypes associated with normal and mutant phenylalanine hydroxylase alleles have been identified in 33 Danish families with children with phenylketonuria. Of the 66 mutant alleles analyzed, 59 (89%) were associated with only four haplotypes. The identification of individual phenylalanine hydroxylase alleles by haplotype analysis enables correlation of the hyperphenylalaninemic phenotypes of the patients with their genotypes. Patients who were either homozygous or heterozygous for the mutant alleles of haplotypes 2 and 3 had a severe clinical course. Patients who had a mutant allele of either haplotype 1 or 4 usually had a less severe clinical phenotype. The recent demonstration that the mutation responsible for classic phenylketonuria associated with haplotype 3 is not present in mutant alleles of other haplotypes provides unambiguous evidence that there are multiple mutations in the phenylalanine hydroxylase gene and supports the hypothesis that different combinations of mutant alleles may be responsible for the clinical diversity of phenylketonuria.