Inborn Error of Metabolism - Diagnostic Techniques

Diagnostic Techniques

Dozens of congenital metabolic diseases are now detectable by newborn screening tests, especially the expanded testing using mass spectrometry. This is an increasingly common way for the diagnosis to be made and sometimes results in earlier treatment and a better outcome. There is a revolutionary GC/MS based technology with an integrated analytics system, which has now made it possible to test a newborn for over 100 genetic metabolic disorders.

Because of the multiplicity of conditions, many different diagnostic tests are used for screening. An abnormal result is often followed by a subsequent "definitive test" to confirm the suspected diagnosis.

Common screening tests used in the last sixty years:

• Ferric chloride test (turned colors in reaction to various abnormal metabolites in urine)
• Ninhydrin paper chromatography (detected abnormal amino acid patterns)
• Guthrie bacterial inhibition assay (detected a few amino acids in excessive amounts in blood) The dried blood spot can be used for multianalyte testing using Tandem Mass Spectrometry (MS/MS). This given an indication for a disorder. The same has to be further confirmed by enzyme assays, GC/MS or DNA Testing.
• Quantitative measurement of amino acids in plasma and urine
• Urine organic acid analysis by Gas chromatography-mass spectrometry
• Plasma acylcarnitines analysis by mass spectrometry
• Urine purines and pyrimidines analysis by Gas chromatography-mass spectrometry

Specific diagnostic tests (or focused screening for a small set of disorders):

• Tissue biopsy or necropsy: liver, muscle, brain, bone marrow
• Skin biopsy and fibroblast cultivation for specific enzyme testing
• Specific DNA testing