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Organic acid profile
Indications for organic acids profile testing in urine:
  1. The clinical picture of metabolic disorders may be variable, non-specific, and can occur at any age. Below is a list of indications for performing an analysis of organic acids in urine:

    • lethargy, coma, seizures or vomiting in a newborn;
    • metabolic decompensation (i.e. clinical deterioration caused by various risk factors, e.g. infection, diarrhoea, vomiting);
    • hyperammonaemia;
    • hypoglycaemia;
    • siblings with a similar clinical presentation;
    • abnormal results in a newborn screening programme;
    • symptoms or syndromes of unexplained origin (idiopathic):
      • metabolic acidosis or lactate acidosis,
      • alkalosis,
      • global developmental delay or developmental regression,
      • liver dysfunction,
      • epilepsy and other neurological symptoms.

    The above list is not complete. The doctor may decide on other indications for performing a urine organic acid analysis.

  2. The analysis of organic acid profiles is a complementary to dried blood spot testing by the LC-MS/MS method in the identification of inborn defects of metabolism. Many metabolic disorders, such as those in the amino acid pathway, have a characteristic profile in both GC-MS and LC-MS/MS analyses, therefore both methods together confirm the diagnosis. There are many diseases that are not covered by the newborn screening programme in Poland due to the specificity of the method, such as 2-hydroxyglutaric aciduria, fumaric aciduria, or alkaptonuria. In such cases, the organic acid profile in urine by GC-MS plays a crucial role in diagnosis.
  3. The newborn screening programme for rare metabolic disorders was implemented gradually in Poland. The entire country was only covered by it at the end of 2013. As a result, an issue remains of individuals born before the programme was implemented and not screened, who may potentially be ill but remain asymptomatic or sparsely symptomatic until a triggering factor for metabolic decompensation occurs.
  4. The advantage of the method is the possibility of providing additional information that can help with diagnosis and/or be useful for monitoring treatment, including measuring of methylmalonic acid levels in response to vitamin B12.
Substances analysed:

Based on the analysis of the obtained chromatogram and mass spectra, and considering available clinical data, levels of dozens of organic compounds present in the test sample are evaluated. The result of the analysis is descriptive. If the profile deviates from the norm, pathological metabolites (the concentration of some metabolites is determined semi-quantitatively) and possible causes of the deviations, and potential indications for further diagnostics are listed.

Due to the variety of excreted compounds, analysis of the OA profile allows for identification not only of typical markers, characteristic of a particular disease entity, but also of other metabolites related to the patient's clinical condition, especially decompensation, diet, or treatment. In such cases, the test result may guide medical management towards further differential diagnosis with other diagnostic methods.

The OA profile describes metabolites related to:

  • disorders of amino acid metabolism (classical organic aciduria, branched-chain amino acid metabolism disorder not classified as organic aciduria, urea cycle disorder and congenital hyperammonaemia, metabolism disorder of phenylalanine, tyrosine, histidine, tryptophan or lysine, gamma-glutamyl cycle disorder and others);
  • abnormal cellular energy metabolism and mitochondrial dysfunction, such as 2-ketoglutaric acid and other Krebs cycle metabolites (fumaric acid, malic acid), 3-methylglutaconic acid;
  • abnormal fatty acid oxidation, including 3-hydroxybutyric acid and acetoacetic acid (ketone bodies) and the presence of dicarboxylic aciduria (DCA), including adipic, suberic, and sebacic acids and their unsaturated and 3-hydroxy derivatives;
  • disorders of carbohydrate metabolism, e.g., glycerol;
  • liver dysfunction: p-hydroxyphenylpyruvic acid (PHPPA) and p-hydroxyphenyllactic acid (PHPLA);
  • renal dysfunction: malic acid, fumaric acid;
  • digestive disorders and bacterial metabolism processes (intestinal mucosa dysfunction and/or dysbiosis): succinic acid, hippuric acid, cresol;
  • disorders of the metabolism of vitamins, mineral elements and other micronutrients (e.g., folic acid, vitamin B12, B2, B6, coenzyme Q, biotin): methylmalonic acid, glutaric acid, 3-hydroxyisovaleric acid;
  • neurotransmitter disorders (dopamine, adrenaline, noradrenaline): homovanillic acid, vanillylmandelic acid, 5-hydroxyindoleacetic acid;
  • glycolytic pathway: pyruvic acid, lactic acid;
  • medications, including valproic acid, paracetamol, salicylates;
  • nutrition: nutramigen, MCT (medium-chain triglycerides), and others;
  • poisoning, e.g., with ethyl alcohol.

Analysis of organic acid profile in urine performed at Masdiag Laboratory is subject to international quality control by ERNDIM (European Research Network for Evaluation and Improvement of Screening, Diagnosis and Treatment of Inherited Disorders of Metabolism).

Detected diagnostic profiles of organic acids in urine:
  1. Typical dicarboxylic aciduria for MCAD deficiency
  2. Ethylmalonic aciduria (EMA)
  3. Formiminoglutamic aciduria (FIGLU)
  4. Fumaric aciduria
  5. Glyceric aciduria
  6. Glutaric aciduria type I (GAI)
  7. Glutaric aciduria type II (MAD deficiency)
  8. Homogentisic aciduria (also known as alkaptonuria)
  9. 2-hydroxyglutaric aciduria (2HGA)
  10. 3-hydroxyisovaleric aciduria (3HIB)
  11. 4-hydroxybutyric aciduria (4HBA)
  12. 3-hydroxy-3-methylglutaric aciduria (HMG)
  13. Isovaleric aciduria (IVA)
  14. 2-ketoadipic aciduria (also known as 2-aminoadipic aciduria)
  15. Malonic aciduria (MCD)
  16. 3-methylglutaconic aciduria (3MGA)
  17. 2-methyl-3-hydroxybutyric aciduria (MHBD)
  18. Methylmalonic aciduria (untreated) (MMA)
  19. Mevalonic aciduria (MVA)
  20. N-acetylaspartic aciduria (also known as Canavan disease)
  21. Oroic aciduria (untreated) (ORA)
  22. Propionic aciduria (PA)
  23. Aminoacylase 1 deficiency (ACY1)
  24. Biotinidase deficiency (untreated)
  25. β-ketothiolase deficiency (BKT)
  26. Kynureninase deficiency (also known as hydroxykynureninuria)
  27. Phenylketonuria (untreated) (PKU)
  28. Glyceroluria
  29. Hawkinsinuria
  30. Hyperoxaluria
  31. Isobutyrylglycineuria (IBG)
  32. Combined methylmalonic and malonic aciduria (CMAMMA)
  33. 3-methylcrotonylglycineuria (3-MCC)
  34. Neuroblastoma (untreated)
  35. 5-oxoprolinuria (also known as pyroglutamic aciduria)
  36. Typical profile for maple syrup urine disease - MSUD (untreated)
  37. Typical profile for combined carboxylase deficiency (untreated)
  38. Tyrosinemia type I (untreated)
  39. Uracil-thymineuria
  40. Dihydrouracil-dihydrothymineuria
  41. Hyper-IgD syndrome