The pathogenesis of phenylketonuria

Written by Hu Qi Feng

Pediatrics

Updated on September 02, 2024

00:00

00:00

Phenylketonuria is an amino acid metabolic disease caused by a deficiency of phenylalanine hydroxylase. Phenylalanine is an essential amino acid for the human body, and it is partially converted into tyrosine by phenylalanine hydroxylase. Due to the reduced activity of phenylalanine hydroxylase, phenylalanine cannot be transformed into tyrosine. This leads to extremely high concentrations of phenylalanine in the blood, cerebrospinal fluid, and tissues. Through alternative metabolic pathways, large amounts of phenylpyruvic acid, phenylacetic acid, phenyllactic acid, and others are produced. High concentrations of phenylalanine and its metabolic products can cause brain damage.

Other Voices

home-news-image

Written by Yan Xin Liang

Pediatrics

48sec

home-news-image

Phenylketonuria lacks what enzyme?

Phenylketonuria is an autosomal recessive genetic disorder primarily caused by mutations in the phenylalanine hydroxylase gene. This leads to reduced activity of phenylalanine hydroxylase, accumulation of phenylalanine and its metabolites in the body, and the onset of the disease. Phenylketonuria is the most common congenital amino acid metabolism disorder. Clinically, it is mainly characterized by intellectual developmental delays, light skin and hair pigmentation, and a mousey urine odor. The incidence of this disease varies by ethnicity and region. In China, the incidence is approximately 1 in 11,000.

home-news-image

Written by Zeng Hai Jiang

Pediatrics

45sec

home-news-image

Can phenylketonuria be breastfed?

Once a child with phenylketonuria is diagnosed, natural diets should be ceased and a low-phenylalanine diet treatment should be initiated. Treatment with a low-phenylalanine formula should continue at least until the age of 12. Breast milk is the ideal natural food for infants; therefore, although breastfeeding should be temporarily halted after diagnosis, it should not be completely stopped so that it can be promptly reintroduced once blood phenylalanine levels are controlled. When blood phenylalanine levels are controlled to an ideal concentration, gradually reintroduce small amounts of natural diet, preferably starting with breast milk, as it contains only one-third the phenylalanine content of cow's milk.

home-news-image

Written by Yan Xin Liang

Pediatrics

53sec

home-news-image

How is phenylketonuria tested?

Phenylketonuria is a treatable inherited metabolic disease, and early diagnosis is essential for early treatment. Currently, we have generally implemented a newborn disease screening system that requires collecting peripheral blood by pricking the heel of newborns after three days of breastfeeding, dropping the blood onto specialized filter paper and sending it to a screening laboratory for phenylalanine concentration measurement. If the concentration exceeds the confirmed value, further differential diagnosis and confirmation are needed. If treatment can begin early, especially within two to three weeks after birth, the prognosis is generally good. Normally, the concentration is less than 120 µmol/L; a fetal concentration of 1200 µmol/L would be considered mild phenylketonuria.

home-news-image

Written by Yan Xin Liang

Pediatrics

1min 9sec

home-news-image

Phenylketonuria is caused by a deficiency in which enzyme?

Phenylketonuria is a common autosomal recessive genetic disorder and is the most common congenital disorder of amino acid metabolism. Clinically, its main features are intellectual disability, light skin and hair pigmentation, and a mouse-like urine odor. The disease is primarily due to a deficiency of phenylalanine hydroxylase, which inhibits the conversion of phenylalanine to tyrosine, leading to increased concentrations of phenylalanine in the blood, cerebrospinal fluid, and various tissues. Due to the obstruction of the main metabolic pathway, the secondary metabolic pathway is enhanced. Under the action of transaminase, phenylalanine undergoes deamination to produce a large amount of phenylpyruvic acid, which, through oxidation, generates side metabolic products such as phenylacetic acid, phenyllactic acid, and para-hydroxyphenylpyruvic acid, which are then excreted in high amounts in the urine. The high concentrations of phenylalanine and its metabolic byproducts accumulate in the brain tissue, causing damage to brain cells.

home-news-image

Written by Yan Xin Liang

Pediatrics

47sec

home-news-image

What is the probability of phenylketonuria?

Phenylketonuria is an autosomal recessive genetic disorder primarily caused by mutations in the phenylalanine hydroxylase gene, leading to reduced enzyme activity and the accumulation of phenylalanine and its metabolites in the body, resulting in the disease. Phenylketonuria is the most common congenital amino acid metabolism disorder, with clinical manifestations mainly including intellectual developmental delays, light skin and hair pigmentation, and a mouse urine odor. The incidence of the disease varies by race and region. In China, the incidence of phenylketonuria is approximately 1 in 11,000, meaning that about one in 11,000 children suffers from phenylketonuria.