Significance of the in vivo deuterated phenylalanine load for long-term phenylalanine tolerance and psychointellectual outcome in patients with PKU

@article{Trefz2005SignificanceOT,
  title={Significance of the in vivo deuterated phenylalanine load for long-term phenylalanine tolerance and psychointellectual outcome in patients with PKU},
  author={Friedrich Trefz and U. Batzler and T K{\"o}nig and Ute Michel and E. Schmidt and Hildgund Schmidt and Horst Bickel},
  journal={European Journal of Pediatrics},
  year={2005},
  volume={149},
  pages={25-27}
}
In 20 patients with PAH deficiency, in vivo RA was determined by an intravenous deuterated Phe load. Sixteen patients had RAs of less than 0.4% of normal, 3a clearly detectable activity between 0.8 and 1.4% of normal. Long-term Phe tolerance as measured by the distribution of plasma Phe levels in categories (0–3.9, 4.0–9.9, 10–15.9 and over 16 mg/dl) was much improved in patients with RAs greater than 0.8%. There was a negative correlation between RA and number of plasma Phe levels >16 mg/dl… 
Phenylalanine tolerance can already reliably be assessed at the age of 2 years in patients with PKU
TLDR
Pre-treatment Phe is unreliable but Phe tolerance is a reliable predictor of the tolerance at 10  years of age, starting at 2 years of age.
Study design and description of patients
TLDR
A West German multicentre study of PKU was designed in 1976 and enrolling patients resulted in the detection of 2 patients with a PTPS-deficiency, and of 163 with an apo-enzyme defect.

References

SHOWING 1-10 OF 17 REFERENCES
PKU and NON‐PKU Hyperphenylalaninemia: Differentiation, Indication for Therapy and Therapeutic Results
TLDR
Psychomotor development in 32 untreated patients with PAHD and Restriction fragment length polymorphism (RFLP) haplotypes at the phenylalanine hydroxylase (PAH) locus showed that 90% of the mutant alleles are confined to four distinct haplotypes.
Effect of age at loss of dietary control on intellectual performance and behavior of children with phenylketonuria.
TLDR
It is suggested that phenylalanine restriction should continue after the age of eight years in children with phenylketonuria, and the highest correlation between the IQs of the children with PKU and their respective parents was observed among the children still on the diet at the age.
Predictors of intelligence quotient and intelligence quotient change in persons treated for phenylketonuria early in life.
TLDR
Diet discontinuation and the natural (off diet) blood phenylalanine level best predicted IQ loss, suggesting that diet continuation may be important for children with natural blood phenYLalanine levels greater than 18 mg/dL.
An ammo-acid substitution involved in phenylketonuria is in linkage disequilibrium with DNA haplotype 2
TLDR
Direct hybridization analysis of the point mutation using a specific oligonucleotide probe demonstrated that this mutation is also in linkage disequilibrium with RFLP haplotype 2 alleles that make up about 20% of mutant PAH genes.
Phenylalaninaemia. Differential diagnosis.
TLDR
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.
Study design and description of patients
TLDR
A West German multicentre study of PKU was designed in 1976 and enrolling patients resulted in the detection of 2 patients with a PTPS-deficiency, and of 163 with an apo-enzyme defect.
Molecular genetics of phenylketonuria in Mediterranean countries: a mutation associated with partial phenylalanine hydroxylase deficiency.
TLDR
The characterization of a mutation in the phenylalanine hydroxylase (PAH) gene associated with partial residual activity of the enzyme is reported, which is linked to an original and rare RFLP haplotype at the PAH locus found in south Europe and North Africa.
Phenylalanine hydroxylase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase gene.
TLDR
The data support previous biochemical and clinical observations that PKU is a heterogeneous disorder at the gene level and demonstrate that the mutation in the gene causes the synthesis of an unstable protein in the cell corresponding to a CRM- phenotype.
...
1
2
...