Inborn Errors of Metabolism : Signs, Symptoms, Diagnosis And Treatment

Inborn Errors of Metabolism

Inborn Errors of Metabolism are the result of a single gene disorder as a result of defects in the biochemical pathways of the body. Although these disorders are individually rare, collectively they feed for the inability of childhood and an important part of the death. Most disorders are inherited as autosomal recessive while autosomal dominant and X-linked disorders are also present. Due to toxic substrate, product deficiency, or accumulation of both, clinical symptoms and symptoms arise. Based on the residual activity of low enzyme, the beginning of clinical photo may start from the infancy to adulthood. Hundreds of disorders have been described so far and there have been considerable clinical overlap between some innate errors. As a result of this fact, the definitive diagnosis of congenital errors depends on enzyme assays or genetic testing. Especially during recent years, important achievements have been achieved for the biological and genetic diagnosis of congenital errors. Techniques such as tandem mass spectrometry and gas chromatography for bio-chemical diagnosis and micro-organisms and the next generation sequencing for genetic diagnosis have enabled rapid diagnosis. Achievements for diagnosis also enabled neonatal screening and prenatal diagnosis. Parallel to the development of clinical methods; Significant progress has also been received for the treatment. Special diet like diet, enzyme replacement therapy, substrate obstruction, and organ transplantation are widely used. It is clear that with the help of preclinical and clinical research done for congenital errors, better diagnostic methods and better treatment approaches will be available.

Inborn Errors of Metabolism make a large range of genetic disorders, including birth defects of metabolism. The majority are due to single-gene defects, which are the codes for enzymes that facilitate converting various substances (substrates) into others (products). In most disorders, due to the accumulation of substances that are toxic or interfere in normal function, or are produced due to the effect of the ability to synthesize essential compounds. Inborn Errors of Metabolism are often known as congenital metabolic diseases or inherited metabolic disorder. The Inborn Errors of Metabolism was made in 1908 by the British physician Archibald Garod (1857-19 36). He is known for the work that predicts “a gene-enzyme enzyme” hypothesis based on his study on nature and heritage of Alkaptonuria. His original text, Inborn Errors of Metabolism, was published in 1923.

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Signs and Symptoms

Due to the overwhelming number of these diseases and the wide range of systems being affected, in almost every “submitted complaint”, congenital metabolic disease may possibly lead to congenital metabolic disease as a possible cause for childhood. The following are examples of possible manifestations affecting the following major organ systems:

•  Development failure, failure to grow, weight loss
•  Uncertain genitalia, delay in puberty, unstable puberty
•  Development delay, tourism, dementia, encephalopathy, stroke
•  Deafness, blindness, pain agnosia
•  Skin beats, abnormal pigment, lack of pigment, excessive hair growth, lump and collision
•  Medical abnormalities
•  Immunodeficiency, low platelet count, low red blood cell count, increased spleen, extended lymph nodes
•  Many forms of cancer
•  Recurrent vomiting, diarrhea, abdominal pain
•  Excessive urination, kidney failure, dehydration, edema
•  Low blood pressure, heart failure, increased heart, high blood pressure, myocardial infarction
•  Liver enlargement, jaundice, liver failure
•  Unusual facial features, congenital malformations
•  Excessive breathing (hyperventilation), respiratory failure
•  Abnormal behavior, depression, psychology
•  Joint pain, muscle weakness, cramps


Dozens of congenital metabolic diseases can now be traced through neonatal screening tests, especially on extended scale using spectrometry largely. This is usually a common method for diagnosis and sometimes results in earlier treatment and better results. A revolutionary gas chromatography-mass spectrometry-based technology with a integrated analytical system, which has now made it possible to test newborns for 100mm genetic metabolic disorders.

Due to the abundance of circumstances, many different diagnostic tests are used for screening. An abnormal result is often followed by a later “definitive test” to confirm suspected diagnosis.

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Common screening tests used in the last sixty years:
•  Ferric chloride test (color change in response to various unusual metabolites in urine)
•  Ninhydrine paper chromatography (abnormal amino acid pattern detected)
•  Guthrie Bacterial Inhibition Assay (Some amino acids in excessive amounts in the blood are detected) The place of dry blood can be used for multidimensional testing using the Tandem Mass Spectrometry (MS / MS). It gave a hint for a disorder. Enzyme assays, IEX-Ninhydrine, GC / MS or DNA testing should be further confirmed.
•  Quantitative measurement of amino acids in plasma and urine
•  IEX-Ninhydrine Post column derivation Liquid ion-exchange chromatography (abnormal amino acid pattern and quantitative analysis detected)
•  Gas Chromatography – Urine Organic Acid Analysis by Mass Spectrometry
•  Analysis of plasma acylcarnitines by mass spectrometry
•  Gas Chromatography – Urine purines and pyrimidines analysis by mass spectrometry

Specific diagnostic tests (or screening centered for a small set of disorders):
•  Tissue biopsy or necropsy: liver, muscles, brain, bone marrow
•  Skin Biopsy and FibroBlast Farming for Specific Enzyme Tests
•  Specific DNA test
It is reported in a 2015 review that even with all these clinical trials, there are cases where “biochemical testing, gene sequencing, and enzymatic tests can neither confirm nor cancel the IEM, whose As a result, the patient needs to rely on the clinical course. ”


In the mid-20th century, there was a ban on the main dietary diet proteins for some amino acid disorders and management of all other care complications. In the last twenty years, enzyme replacement, gene therapy, and organ transplants have become available and beneficial for many previously unexpected disorders. Some more common or promising treatments are listed:

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Dietary restrictions
•  For example, decrease in dietary protein is the main basis for treatment for phenylketonuria and other amino acids.
Dietary supplement or replacement
•  For example, oral injection of cornstarch often helps in preventing people from becoming hypoglycemic by glycogen storage diseases several times a day.
•  For example, thiamine supplements benefit many types of disorders that cause lactic acidosis.
•  Intermediarium metabolites, compounds, or medicines that facilitate or diminish specific metabolic pathways
•  Dialysis
•  Enzyme replacement E.g. Acid-alpha glucosidase for Pompe disease
•  Gene therapy
•  Bone marrow or organ transplantation
•  Treatment of symptoms and complications
•  Prenatal diagnosis

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