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Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in all proteins and in some artificial sweeteners. If PKU is not treated, phenylalanine can build up to harmful levels in the body, causing intellectual disability and other serious health problems. Mutations in the PAH gene cause phenylketonuria. The PAH gene provides instructions for making an enzyme called phenylalanine hydroxylase. This enzyme converts the amino acid phenylalanine to other important compounds in the body. The most severe form of this disorder is known as classic PKU.

Infants with classic PKU appear normal until they are a few months old. Without treatment, these children develop permanent intellectual disability.Seizures, delayed development, behavioral problems, and psychiatric disorders are also common. Untreated individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the body. Children with classic PKU tend to have lighter skin and hair than unaffected family members and are also likely to have skin disorders such as eczema.Less severe forms of this condition, sometimes called variant PKU and non-PKU hyperphenylalaninemia, have a smaller risk of brain damage.
People with very mild cases may not require treatment with a low-phenylalanine diet.

Tests Prescribed

  1. New Born Screening/TMS
  2. Urine Organic Acid Test
  3. Plasma Amino Acid Test

About the Prescribed Tests

Test Name Sample Type Method Description
Urine Organic Acid Test 5-10 ml urine in Sterile container or Urinsoaked on 4 Urine Filter Papers Gas Chromatography/Mass Spectrometry (GC/MS) Qualitative report of abnormal levels of organic acids identified
Plasma Amino Acid Test 2-4 ml EDTA Blood Liquid Chromatography/ Mass Spectrometry (LC/MS Amino Acid level test in blood

Test Results

  1. TMS: TMS of this baby revealed significant(18.05) evaluation of phenylalanine & phenyl: tyrosine ratio.
  2. Urine Organic Acid Test: Baby was found to have mild to significant elevated levels of phenylalanine metabolite (Phenyllactic acid, Phenylacetic acid, Phenyl pyruvic acid).
  3. Plasma Amino Acid Test: Plasma amino acidogram shows significant elevation of phenylalanine.

Figure 1: Results Of Urine Organic Test Report

Compound Name Citrulline 41.54
Phenylalanine 1896.41 25.9 - 105
Phenylalanine/Tyrosine ratio 19.07 0.29 - 4.31

Figure 2: Results Of Plasma Amino Acid Test Report

1 Citrulline 41.54 3-35
2 Tyrosine 46.14 22-108
3 Phenylalanine 102.53 31-75


  1. The recommended first-tier test for Phenylketonuria disease is NBS-7, TMS, UOA, followed by PAA.
  2. Individuals with PKU activity higher than the reference range for these assays are more likely to have variants in the PAH gene that are identifiable by NGS-based Exome Sequencing.
  3. Urine Organic Acid is the test done to identify any kind of urea cycle disorder.
  4. Plasma Amino Acid test is done to confirm the levels of phenylalanine and other amino acids to conclude the reports.
  5. Monitor the treatment by periodically measuring plasma amino acid levels of phenylalanine.

This bulletin is compiled by

Name Designation Contribution
Ms. Krishnendu Menon Genetic Counselor Compilation
Mrs. N Sushma Chander Senior Manager/ QualityCoordinator-Biochemical Genetics Biochemical Genetics