RESUMO
Phenylalanine hydroxylase deficiency is a trait inherited in an autosomal recessive pattern; the associated phenotype varies considerably. This variation is mainly due to the considerable allelic heterogeneity in the phenylalanine hydroxylase enzyme locus. We examined the genotype-phenotype correlation in 54 phenylketonuria (PKU) patients from Minas Gerais, Brazil. Two systems were used. The first was a phenotype prediction system based on arbitrary values (AV) attributed to each mutation and the second was a correlation analysis. An AV was assigned to each mutation: AV = 1 for classical PKU mutation; AV = 2 for moderate PKU mutation; AV = 4 for mild PKU mutation, and AV = 8 for non-PKU hyperphenylalaninemia mutation. The observed phenotype for AV analysis was the clinical diagnosis established by the overloading phenylalanine test. Among the 51 PKU patients that we analyzed based on this trait, in 51% the predicted phenotype did not match the observed phenotype; the highest degree of concordance was found in patients with null/null genotypes. The genotype was observed to be a good predictor of the clinical course of the patients and significant correlations were found between phenylalanine values at first interview and predicted residual activity, genotype and arbitrary value sum.
Assuntos
Variação Genética , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/genética , Sequência de Aminoácidos , Brasil , Genótipo , Humanos , Lactente , Mutação , Fenótipo , Fenilcetonúrias/enzimologia , Índice de Gravidade de DoençaRESUMO
This work was undertaken in order to ascertain the PKU mutational spectrum in Minas Gerais, Brazil, the relative frequency of the mutations in the State and the origin of these mutations by haplotype determination. Minas Gerais is a trihybrid population formed by miscegenation from Europeans, Africans and Amerindians. All 13 exons of the PAH gene from 78 PKU patients were analyzed, including splicing sites and the promoter region. We identified 30 different mutations and 98% of the PAH alleles were established. A new mutation (Q267X) was identified as well. The most common mutations found were V388M (21.2), R261Q (16.0%), IVS10-11G>A (15.3%), I65T (5.8%), IVS2+5G>C (5.8%), R252W (5.1%), IVS2+5G>A (4.5%), P281L (3.8%) and L348V (3.2%). These nine mutations correspond to 80% of the PKU alleles in the state. Haplotypes were determined to characterize the origin of the PAH alleles. The majority of the mutations found, with respective haplotypes, are frequent in the Iberian Peninsula. However, there were some mutations that are rare in Europe and four previously unreported mutation-haplotype associations. I65T and Q267X were found in association with haplotype 38 and may be African in origin or the result of miscegenation in the Brazilian population.
Assuntos
Mutação , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/genética , Substituição de Aminoácidos , Brasil/epidemiologia , Análise Mutacional de DNA , Humanos , Fenilcetonúrias/epidemiologiaRESUMO
1. Study of six patients with chronic calcifying pancreatitis (CCP) occurring over a 10 year period, representing an incidence rate of approximately 1:1,000 of the impatients in the children's ward of a general hospital in central Brazil, is reported. 2. Major clinical manifestations as well as therapeutic management are described. 3. The possible relationship between CCP and primary protein-calorie malnutrition is discussed and the importance of a CCP diagnosis when dealing malnourished children who do not respond satisfactorily to common therapy is emphasized
