The pathogenesis of phenylketonuria

Written by Hu Qi Feng

Pediatrics

Updated on September 02, 2024

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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.

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Written by Zeng Hai Jiang

Pediatrics

1min 2sec

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Does phenylketonuria require lifelong dietary control?

Theoretically, phenylketonuria requires lifelong dietary control. Phenylketonuria is caused by a deficiency in phenylalanine hydroxylase in the metabolic pathway of phenylalanine, leading to disordered metabolism of phenylalanine in the liver. Phenylketonuria is the first genetic metabolic disease that can be managed through diet. Since natural foods all contain certain amounts of phenylalanine, once diagnosed, affected children should cease consuming natural diets and should be treated with a low-phenylalanine diet. Treatment with a low-phenylalanine formula should continue at least until the age of 12. When the concentration of phenylalanine in the blood is controlled at an ideal level, natural foods can gradually be reintroduced in small amounts. The reintroduction of food should still follow the principles of low protein and low phenylalanine. The types and amounts of food that each child can add vary individually and are related to the severity of the enzyme deficiency.

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Written by Zeng Hai Jiang

Pediatrics

52sec

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Do adults with phenylketonuria need to eat special food?

Phenylketonuria may not necessarily require a special diet in adulthood. It is the first genetic metabolic disorder that can be treated through dietary control. Natural foods all contain a certain amount of phenylalanine, so once children with phenylketonuria are diagnosed, they should stop their natural diet and instead be given a low-phenylalanine diet. Low-phenylalanine formula treatment should continue at least until the age of 12. When the concentration of phenylalanine in the blood is controlled at an ideal level, a gradual addition of natural foods can be made. Larger infants and children can add foods such as milk, porridge, noodles, and eggs. However, these added foods should still primarily be low in protein and low in phenylalanine.

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Written by Yan Xin Liang

Pediatrics

1min 1sec

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How is phenylketonuria diagnosed?

How is phenylketonuria diagnosed? Firstly, we start with screening, which is usually done when the newborn is 3 to 7 days old by heel prick to collect peripheral blood, which is then dropped onto specialized filter paper for the determination of phenylalanine concentration. If the concentration of phenylalanine is above the cutoff value, further determination of phenylalanine concentration is conducted. The normal concentration is less than 120 umol/L. If the concentration of phenylalanine is greater than 1200 umol/L, it suggests severe phenylketonuria. Moderate levels are above 360 umol/L, and mild levels are above 120 umol/L but less than 360 umol/L. Furthermore, diagnosis can be confirmed through DNA analysis, currently available tests include screening for mutations in the phenylalanine hydroxylase gene.

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Written by Hu Qi Feng

Pediatrics

43sec

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Mechanism of phenylketonuria

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

52sec

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Clinical symptoms of phenylketonuria

The clinical symptoms of phenylketonuria generally include normal appearance at birth, with symptoms usually appearing between three to six months, and becoming more pronounced by the age of one. The most noticeable initial symptoms involve the nervous system; delayed intellectual development is prominent, with intelligence often below normal, along with behavioral abnormalities such as hyperactivity, depression, restlessness, and withdrawal. There could be minor epileptic seizures, and in some cases, increased muscle tone or exaggerated tendon reflexes. Regarding the skin, several months after birth, due to insufficient melanin synthesis, the child’s hair changes from black to yellow, the skin appears pale, and eczema is also relatively common. Additionally, the urine and sweat contain higher levels of phenylacetic acid, which can result in a distinctive mouse-like urine odor.