Genotype-phenotype correlations in phenylketonuria.

  title={Genotype-phenotype correlations in phenylketonuria.},
  author={Friedrich Trefz and Peter Burgard and T K{\"o}nig and B. Goebel-Schreiner and Uta Lichter-Konecki and David S. Konecki and E. Schmidt and Hildgund Schmidt and Horst Bickel},
  journal={Clinica chimica acta; international journal of clinical chemistry},
  volume={217 1},
  • F. Trefz, P. Burgard, H. Bickel
  • Published 30 July 1993
  • Medicine
  • Clinica chimica acta; international journal of clinical chemistry
Phenylalanine hydroxylase genotypes, predicted residual enzyme activity and phenotypic parameters of diagnosis and treatment of phenylketonuria
The quality of dietary control was independent of the genotype, indicating that the outcome of therapy can be successfully manipulated in spite of the genetic make-up.
Molecular Diagnosis of Phenylketonuria: From Defective Protein to Disease-Causing Gene Mutation
The base for molecular diagnosis, genetic counseling and selection of BH4-responsive PKU patients in Serbia was created and it was shown that there is a significant correlation between mutant PAH genotypes and PKU phenotypes.
Genetics of Phenylketonuria: Then and Now
A greater understanding of the relationships between individual gene variant, residual PAH activity, tetrahydrobiopterin (BH4) responsiveness, and the clinical PKU phenotype may increase the potential for individualized management of PKU in future.
Human phenylalanine hydroxylase mutations and hyperphenylalaninemia phenotypes: a metanalysis of genotype-phenotype correlations.
The majority of PAH mutations confer a consistent phenotype and that this is concordant with their effects, when known, predicted from in vitro expression analysis, however, significant inconsistencies reveal that the HPA-phenotype is more complex than that predicted by Mendelian inheritance of alleles at the PAH locus.
The PAH gene, phenylketonuria, and a paradigm shift
The PKU story contains many messages, including: a framework on which to appreciate the complexity of PKU in which phenotype reflects both locus‐specific and genomic components; what the human PAH gene tells us about human population genetics and evolution of modern humans; and how the interest in PKU is served by a locus-specific mutation database.
In vivo disposal of phenylalanine in phenylketonuria: A study of two siblings
Two siblings of different sex and identical genotype at the PAH locus who demonstrate a difference in phenylalanine disposal are reported.
The relationship of genotype to phenotype in phenylalanine hydroxylase deficiency.
It is concluded that dietary restriction of phenylalanine neonatally and good control contributed to normal intellectual development and Continuation of dietary treatment into adulthood appeared to improve academic achievement in patients with severe phenylAlanine hydroxylase mutations.
Genotype and Intellectual Phenotype in Untreated Phenylketonuria Patients
It is proposed that another gene or genes may be modifying the intellectual phenotype of untreated patients with untreated phenylketonuria, and Tyrosine hydroxylase was chosen as a candidate gene, because it can perform the same reaction as PAH.
Molecular Correlations in Phenylketonuria: Mutation Patterns and Corresponding Biochemical and Clinical Phenotypes in a Heterogeneous California Population
There is no correlation of mutation severity with either pretreatment PHE levels or IQ measurement in treated patients, and genetic counseling in PKU should incorporate the notion that prognosis may not be predicted with precision based on mutation analysis in a given patient.


Molecular basis of phenotypic heterogeneity in phenylketonuria.
The hypothesis that there is a molecular basis for phenotypic heterogeneity in phenylketonuria is supported and the establishment of genotype will aid in the prediction of biochemical and clinical phenotypes in patients with this disease.
Phenylalaninaemia. Differential diagnosis.
Evidence provided by family studies supports the concept that the phenylalaninaemias are genetically distinct and a classification scheme derived primarily from these studies is suggested which includes two forms of phenylketonuria (PKU) and four forms of Phenylalanineemia (variants) unrelated to abnormalities in tyrosine metabolism.
Intellectual development in 12-year-old children treated for phenylketonuria.
Data support a recommendation that dietary restriction of phenylalanine should be maintained through adolescence, and show no deficits in test scores, except for arithmetic, which declined between ages 6 and 12 years in 90% of the children in this study.
Status report on phenylketonuria treatment: 1990.
  • C. Mabry
  • Medicine
    American journal of diseases of children
  • 1991
The Collaborative Study of Children Treated for Phenylketonuria reports the status of 95 of these children who have reached age 12 years, a milepost age in the study, and documented even more conclusively that the sooner the low phenylalanine diet is begun, the better the outcome.
Phenylketonuria with normal intelligence.
  • D. Primrose
  • Medicine
    Journal of mental deficiency research
  • 1983
A review was made of the literature with respect to cases of untreated phenylketonuria (PKU) with normal intelligence, and possible reasons for the preservation of intelligence in the affected individual with an IQ of 82.
Phenylketonuria: Biochemical Mechanisms
This review of phenylketonuria will be neither comprehensive nor encyclopedic, but will be limited to those aspects of the disease where sufficient biochemical knowledge is available to support meaningful discussion—admittedly, often speculative—about underlying mechanisms.