Classic Phenylketonuria (PKU):
• It occurs as a result of the absence or lack of phenylalanine hydroxylase activity, which is responsible for the conversion of phenylalanine to tyrosine.
• The phenylalanine gene is located on the 12th chromosome.
• OR passes. Turkey is one of the most common countries in the world (1:4000).
• Phenylalanine accumulates in the blood and causes toxic effects.
• Phenylalanine metabolites are excreted in the urine. Metabolites increased in urine and sweat:
Phenylpyruvic acid,
phenyllactic acid,
Phenylacetic, hydroxyphenylacetic acid and
Phenylacetyl glutamine increases.
Clinical findings
• Mental motor retardation and growth retardation, microcephaly
• Spasticity, hypereflexia, tremor, convulsion
• Hyperactivity, autistic behavioral changes (rhythmic shaking, aimless hand movements)
• Light skin, eye and hair color (increased phenylalanine inhibits tyrosinase, tyrosine and melanin production decreases)
• Eczematous skin lesions
• A rat-dead or moldy odor in the urine
• Patients with persistent vomiting in the first 1-2 months may be confused with pyloric stenosis.
• Phenylacetic acid gives off the characteristic rat-dead (mold) odor
• Phenylpyruvic acid causes color change in FeCl3 test.
Non-PKU Mild Hierphenylalaninemia:
• Phenylketones are not seen in the urine in these children whose phenylalanine level is above 2 mg/dl but below 20 mg/dl.
• Patients are given a diet again. In addition, some may be responsive to the cofactor (BH4).
Tetrahydrobiopterin (BH4 Deficiencies (Malignant Phenylketonuria):
• Although BH4 is a cofactor of phenylalanine hydroxylase, dopamine and serotonin synthesis are also impaired because it regenerates cofactors of both tyrosine hydroxylase (tyrosinase) and tryptophan hydroxylase.
• Serotonin (synthesized from tryptophan) and dopamine (synthesized from tyrosine) levels are low in the CNS.
• The disease manifests itself with extrapyramidal symptoms (axial hypotonia, choreoathetotic or dystonic movements, hypokinesia), convulsions, mental retardation, hypersalivation and swallowing difficulties.
• Since these patients have hyperprolactinemia due to dopamine deficiency, serum prolactin measurement gives an idea about the neurotransmitter level in the brain.
Diagnosis in phenylketonuria:
• Babies are normal at birth. With the start of feeding, symptoms begin to appear with an increase in plasma phenylalanine.
• Guthrie test is used as a screening test to show increased phenylalanine in serum. The Guthtrie test is based on the reproduction of Bacillus subtilis using phenylalanine in the heel blood.
• In order for the blood phenylalanine level to rise, the baby must have fed at least 2-3 times. Therefore, the blood sample is 24-48. should be taken within hours. Today, measurements with tandem MS instead of the Guthrie test have reduced false positives.
• The blue-green color that occurs when three drops of 10% FeCl3 are dropped into six drops of urine indicates the presence of phenylketones in the urine.
Diagnosis in Classical Phenylketonuria
• Elevated plasma phenylalanine level
• Normal or low serum tyrosine level (increased Phe/Tyr ratio)
• Increase in phenylalanine metabolites in the urine
• Not low concentration of cofactor tetrahydrobiopterin in plasma (may be high or normal)
• No significant decrease in phenylalanine levels within 4-8 hours with the BH4 challenge test
Treatment
Classic PKU
• In the first 12 years, a strict but life-long phenylalanine-restricted diet is applied.
• Excessive restriction of phenylalanine intake results in protein deficiency:
- anemia
- lethargy
- rashes
- Diarrhea
- Growth and development retardation
- May cause deficiency symptoms such as death.
Atypical alig) PKU:
• Diet therapy and synthetic BH4 sapropterin dihydrochloride (Kuvan) therapy is given. Neurotransmitter precursors (L-dopa, 5-0H tryptophan) are given
Maternal Phenylketonuria:
If the mother has phenylketonuria and/or the blood phenylalanine level rises due to pregnancy, the fetus is affected and congenital malformations occur.
• Premature, intrauterine growth retardation
• Mental retardation, microcephaly
• Congenital heart anomaly
• Esophageal atresia, intestinal malrotation
• Ocular disorder
The mother should start a diet before conception and the blood phenylalanine level should be between 2-6 mg/dl.