Phenylketonuria is a congenital deficiency of what enzyme?

Written by Yan Xin Liang
Pediatrics
Updated on July 02, 2025
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Phenylketonuria is a common amino acid metabolic disorder caused by a deficiency of enzymes in the phenylalanine metabolic pathway. This deficiency prevents the conversion of phenylalanine into tyrosine, leading to the accumulation of phenylalanine and its keto acids, which are then excreted in large amounts in the urine. The condition is primarily due to a lack of phenylalanine hydroxylase and is a relatively common autosomal recessive genetic disease. Its main clinical manifestations include intellectual disability, psychiatric and neurological symptoms, eczema, skin scratching, pigment loss, and a mouse-like urine odor.

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Written by Yan Xin Liang
Pediatrics
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If phenylketonuria is not treated, what will happen?

Phenylketonuria (PKU) is an amino acid metabolic disorder primarily caused by a deficiency in phenylalanine hydroxylase. This deficiency prevents phenylalanine from being converted to tyrosine, leading to a significant accumulation of phenylalanine, which is then excreted in large quantities in the urine. It is a common genetic metabolic disorder. If not treated, it can lead to developmental delays in children, particularly in intellectual development, with markedly lower IQ than peers, especially noticeable in language development disorders. Additionally, it can also present with neurological and psychiatric symptoms such as agitation, hyperactivity, increased muscle tone, and hyperreflexia. There is also depigmentation of the skin and hair, and the urine may have a mousy odor.

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The earliest manifestation of phenylketonuria

Children with phenylketonuria usually start showing symptoms within 3 to 6 months after birth: Firstly, the nervous system is affected, which can be seen in developmental delays in intelligence, often with IQs lower than normal. Symptoms may include restlessness, depression, hyperactivity, or minor epileptic seizures. A few may exhibit increased muscle tone or heightened tendon reflexes. A few months after birth, due to insufficient melanin synthesis, the skin and hair undergo changes. Hair color may shift from black to yellow, the skin may appear very pale, and eczema is also more common. Additionally, because of the excretion of greater amounts of phenylacetic acids in urine and sweat, there may be a distinct mouse-like urine odor.

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Written by Yan Xin Liang
Pediatrics
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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 Yan Xin Liang
Pediatrics
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Phenylketonuria patients lack phenylalanine hydroxylase.

Phenylketonuria is an autosomal recessive genetic disorder caused by mutations in the phenylalanine hydroxylase gene, leading to reduced enzyme activity and resulting in the accumulation of phenylalanine and its metabolic products in the body, causing the disease. Phenylketonuria is the most common congenital amino acid metabolism disorder, clinically presenting with intellectual developmental delays, lighter skin and hair pigmentation, and a musty urine odor. The disease is mainly caused by mutations in the phenylalanine hydroxylase gene, leading to reduced enzyme activity.

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Written by Hu Qi Feng
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Phenylketonuria Clinical Symptoms

Phenylketonuria may appear normal at birth, but symptoms usually start to appear between three to six months, with the symptoms becoming most evident at one year old. These are often manifestations of the nervous system, with prominent developmental delays in intelligence. The IQ is often lower than normal, and there may be abnormal behaviors, minor epileptic seizures, and, in a few children, increased muscle tone and hyperactive tendon reflexes. Due to insufficient melanin synthesis a few months after birth, affected children’s hair color changes from black to yellow, their skin is fair, and skin eczema is relatively common. Due to the elevated excretion of phenylacetic acid in urine and sweat, there is a distinct mouse-like urine smell.