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It is an inborn error of metabolism caused by defective phenylalanine metabolism.

It is of 5 types:

Type 1, classic phenylketonuria: Due to deficiency of

phenylalanine hydroxylase.

Type 2 and type 3: Due to deficiency of Dihydrobiopterin

reductase (chromosome 4).

Type 4 and type 5: Due to defective Dihydrobiopterin


It is an autosomal recessive disorder caused by mutation in short arm of chromosome 12. Frequency of phenylketonuria is 1 in 1,500

all over the world and in India, it is seen in 1 in 25,000 live births.

Biochemical abnormalities:

Phenylalanine cannot be converted to tyrosine. So, phenylalanine accumulates. When Phenylalanine level in blood is elevated, alternate minor pathways are opened. Compounds like Phenylketone (phenylpyruvate), phenyllactate and phenylacetate are found in urine.

Clinical manifestations

PKU child is mentally retarded usually IQ of 50 is seen. About 20% inmates of lunatic asylum may have PKU. Often clinical manifestations seen as Agitation, hyperactivity, tremors and convulsions. Phenylalanine interferes with neurotransmitter synthesis that leads to common clinical features. Hypopigmentation which is a common clinical finding is due to the inhibition of enzyme tyrosinase. Phenylacetate excreted in sweat causes mousy odor of the body.

Laboratory Diagnosis

Blood phenylalanine level: Normal level is 1 mg/dL. In PKU, the level is 20 mg/dL. This may be demonstrated by chromatography. Tandem mass spectroscopy is the most reliable test.

Guthrie test

Guthrie test is a rapid screening test - Guthrie’s test detects phenylalanine in the blood of newborns, enabling for early diagnosis of PKU Ferric chloride test: Urine of the patient contains phenylketones about 500–3000 mg/day. This could be detected by adding a drop of ferric chloride to the urine. A transient blue-green color is a positive test. But this is a less reliable test.

DNA probes – diagnose the defects in enzymes phenylalanine hydroxylase and dihydrobiopterin reductase.


Early detection is very important. About 5 units of IQ are lost for each 10-week delay in starting the treatment for phenylketonuria. The treatment is to provide a diet containing low phenylalanine (10–20 mg/kg body weight per day).

Food based on tapioca (cassava) will have low phenyl-alanine content.

This special diet with low phenylalanine content is to be continued during the first decade of life; after which the child can have a normal diet. Life-long compliance of special diet is advised, though not mandatory. Female child when becomes adult and become pregnant, again special diet is to be given, because the brain development of the fetus will be affected by increased phenylalanine level.


All of the following are features of Phenylketonuria EXCEPT -

  1. Musty smell
  2. Behavioral problems
  3. Macrocephaly
  4. Seizures

Answer : C

Mother with poorly treated PKU in pregnancy may have a baby with - small head [Microcephaly], and low birth weight.