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 Gas chromatography–mass spectrometry-based technology with an integrated analytics system, which has now made it possible to test a newborn for over 100 mm 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, IEX-Ninhydrin, GC/MS or DNA Testing.&Quantitative measurement of amino acids in plasma and urine&IEX-Ninhydrin post column derivitization liquid ion-exchange chromatography (detected abnormal amino acid patterns and quantitative analysis)&Urine organic acid analysis by gas chromatography–mass spectrometry&Plasma acylcarnitines analysis by mass spectrometry&Urine purines and pyrimidines analysis by gas chromatography-mass spectrometr
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 testin
A 2015 review reported that even with all these diagnostic tests, there are cases when "biochemical testing, gene sequencing, and enzymatic testing can neither confirm nor rule out an IEM, resulting in the need to rely on the patient's clinical course."[3]
Because of the enormous number of these diseases and wide range of systems affected, nearly every "presenting complaint" to a doctor may have a congenital metabolic disease as a possible cause, especially in childhood. The following are examples of potential manifestations affecting each of the major organ systems.
Growth failure, failure to thrive, weight loss&Ambiguous genitalia, delayed puberty, precocious puberty&Developmental delay, seizures, dementia, encephalopathy, stroke&Deafness, blindness, pain agnosia&Skin rash, abnormal pigmentation, lack of pigmentation, excessive hair growth, lumps and bumps&Dental abnormalities&Immunodeficiency, low platelet count, low red blood cell count, enlarged spleen, enlarged lymph nodes&Many forms of cancer&Recurrent vomiting, diarrhea, abdominal pain&Excessive urination, kidney failure, dehydration, edema&Low blood pressure, heart failure, enlarged heart, hypertension, myocardial infarction&Liver enlargement, jaundice, liver failure&Unusual facial features, congenital malformations&Excessive breathing (hyperventilation), respiratory failure&Abnormal behavior, depression, psychosis&Joint pain, muscle weakness, cramps&Hypothyroidism, adrenal insufficiency, hypogonadism, diabetes mellitu