Mechanism of phenylketonuria

Written by Hu Qi Feng

Pediatrics

Updated on September 03, 2024

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Phenylketonuria is characterized by reduced activity of phenylalanine hydroxylase, which fails to convert phenylalanine to tyrosine, causing extremely elevated levels of phenylalanine in the blood, cerebrospinal fluid, and tissues. This leads to the production of large amounts of phenylpyruvic acid, phenylacetic acid, phenyllactic acid, and p-hydroxyphenylacetic acid via alternative pathways. High concentrations of phenylalanine and its metabolic products can cause brain damage, which manifests as developmental intellectual disabilities, changes in skin and hair pigmentation, and a mousy urine odor, all part of a clinical syndrome.

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Written by Yan Xin Liang

Pediatrics

39sec

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Is phenylketonuria characterized only by pale facial skin?

Phenylketonuria is a common amino acid metabolic disorder. It is primarily due to the deficiency of phenylalanine hydroxylase, which prevents the conversion of phenylalanine to tyrosine, leading to a series of clinical symptoms. These can manifest as intellectual disability, neuropsychiatric symptoms, eczema, skin scratching, pigment loss, and a musty odor. The skin whiteness mentioned is not merely facial pallor; it affects the entire skin because the benefits of tyrosine are reduced, leading to decreased melanin synthesis. Consequently, the hair of affected children can also be lighter and tend to be brown.

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Written by Yan Xin Liang

Pediatrics

1min 2sec

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Causes of Phenylketonuria

The cause of phenylketonuria is that phenylalanine is an essential amino acid for the human body. Some of the phenylalanine ingested is used for protein synthesis, while another part is converted into tyrosine by the action of phenylalanine hydroxylase. Only a small amount of phenylalanine undergoes a secondary metabolic pathway and is converted into phenylpyruvate under the action of transaminase. Due to the reduced activity of phenylalanine hydroxylase in affected children, phenylalanine cannot be converted into tyrosine, leading to an extremely high concentration of phenylalanine in blood, cerebrospinal fluid, and tissues. This, through a bypass metabolic pathway, results in the production of a large amount of phenylpyruvate, phenylacetate, phenyllactate, and p-hydroxyphenylacetate. The high concentration of phenylalanine and its metabolic products then leads to brain damage, which is the cause of the disease.

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Written by Yao Li Qin

Pediatrics

1min 24sec

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Phenylketonuria should be treated in which department?

Phenylketonuria is a common autosomal recessive genetic disorder due to a deficiency in the enzymes involved in the metabolic pathway of phenylalanine. It is a genetic metabolic disease. After the birth of a child, newborn screening is conducted for this disease. If a child is diagnosed with phenylketonuria or suspected of having the condition, it is common to visit a pediatric neurology department at a children's hospital. Phenylketonuria mainly causes varying degrees of intellectual disability, and some children may even experience epileptic seizures. Additionally, about 90% of affected children gradually develop lighter skin and hair, reduced iris pigmentation, dry skin, eczema, and a distinctive mouse-like urine odor, which is due to the excretion of phenylacetic acid in urine and sweat. It is a challenging genetic metabolic disorder to treat, requiring special dietary management. It is advisable to bring the child to the pediatric neurology department. Some hospitals may have a specialized department for genetic metabolic diseases. If such a department is available, it is recommended to consult there; otherwise, pediatric neurology is the appropriate alternative.

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Written by Yan Xin Liang

Pediatrics

53sec

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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.

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Written by Zeng Hai Jiang

Pediatrics

42sec

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Can patients with phenylketonuria eat fish and shrimp?

Children with phenylketonuria cannot eat fish and shrimp because phenylketonuria is caused by a deficiency of phenylalanine hydroxylase in the phenylalanine metabolic pathway, leading to metabolic disorder of phenylalanine in the liver. Phenylketonuria is the first hereditary metabolic disease that can be controlled by diet, as natural foods contain certain amounts of phenylalanine. Therefore, once diagnosed, children with phenylketonuria should stop consuming a natural diet and should be treated with a low phenylalanine diet. Fish and shrimp contain rich protein and high levels of phenylalanine, hence children with phenylketonuria cannot eat fish and shrimp.