Akademik Veri Yönetim Sistemi
International Inborn Errors of Metabolism and Nutrition Congress, İstanbul, Türkiye, 10 - 14 Nisan 2019, ss.24-25
is an inherited amino acid metabolism disease caused by the enzyme
phenylalanine hydroxylase (PAH) and / or by the incomplete or inadequacy of
tetrahydrobyopterine (BH4), the cofactor of this enzyme. Enzyme is encoded by
phenylalanine hydroxylase gene (PAH). 955 different PAH mutations reported. Most patients
are heterozygous. R408W is the most common mutation in European patients with PKU.
The biochemical phenotype, by gene genotype, correlates with phenylalanine levels and
phenylalanine (phe) tolerance before treatment. However, neurological, cognitive, and
behavioral phenotypes are not linked to genotypes.
The pathogenesis of brain damage in phenylketonuria is unknown. Generally associated with
high levels of phenylalanine. Patients face progressive, irreversible neurological damage
during infancy and childhood. The most common effect is mental retardation.
Blood phenylalanine level begins to increase with nutrition. Diagnosis can be cdone by
screening test. Blood phe level is key point for diagnosis. Pterins in blood or urine and
dihydropteridine reductase activity in blood are measured for differantial diagnosis of
tetrahydrobiopterin metabolism disorders. For differential diagnosis of
hyperphenylalaninemia we also evaluate gestational week (pretermaturity), sick babies
(especially liver diseases). In these patients, methionine, tyrosine, phenylalanine and leucine
/ isoleucine are generally high. Parenteral nutrition with amino acids chemotherapeutic drug
therapies, trimethoprim use may cause increased phe levels.
Medical Nutrition Therapy is a successful and proven treatment. The main goal is to reduce
the level of blood phe to the level that will prevent neuropathological side effects. On the
other side we should ensure adequate protein intake for protein synthesis according to the
age of the patient. Phe levels f patients under treatment are foolowed. The upper limit for
countries varies, UK> 400 μmol / l, Germany, Turkey (some centers)> 600 mmol / l,America> 360 μmol / l. To stay below these limits patients should have phe restricted diets.
Because PHE is an essential amino acid, excessive restraint can be quite harmful especially
during infancy. This limitation in natural protein consumption emerges the need to be
supplemented with semisynthetic products in order to synthesize enough protein.
BH4 theraphy may decrease the phenylalanine level in patients with BH4-responsive PKU.
Reduction of PAH activity in mouse experiments with mutations of BH4-responsive patients
with mild hyperphenylalaninemia phenotype carrying the Pahenu1 mutation; Misfolding,
Aggregation or Accelerated destruction has been shown to be responsible. All patients,
except those with two null mutations with no known enzyme activity, should be clinically
tested for BH4 responsiveness.
Most adaptable period of childhood and childhood Medical nutrition therapy conflicts with
culturally normal eating habits. This complicates compliance with treatment, especially in
older children and adolescents.
Age of initiation of treatment, Keeping blood phe levels at desired levels, Most importantly
the infancy / childhood phe levels, Duration of Phe deficiency periods, The blood depends
on the personal differences of phe transport in the brain barrier.