What does an isolated increase in urinary excretion of 2,3 dihydroxy-2-methylbutyrate indicate?

From the Guidelines

An isolated increase in urinary excretion of 2,3-dihydroxy-2-methylbutyrate indicates 3-OH-Isobutyryl-CoA hydrolase deficiency or Short-chain enoyl-CoA hydratase deficiency, both of which are rare inborn errors of metabolism. According to the study published in Genetics in Medicine in 2018 1, these disorders are characterized by the elevation of specific metabolites in urine organic acid analysis. The study provides a table of recently described inborn errors of metabolism with abnormalities in urine organic acid analysis, which includes 2,3-Dihydroxy-2-methylbutyric acid as an elevated metabolite in 3-OH-Isobutyryl-CoA hydrolase deficiency and Short-chain enoyl-CoA hydratase deficiency.

• Key points to consider in the interpretation of this finding include:
  • The clinical presentation and medical history of the patient
  • The presence of other abnormal organic acids in the urine
  • The need for follow-up testing, such as molecular studies, to confirm the diagnosis
  • The importance of communication with the ordering physician to accurately interpret the complex chromatogram
• Management of these disorders typically involves avoiding prolonged fasting, following a low-protein diet, and carnitine supplementation, as well as providing glucose to prevent catabolism, correcting acidosis, and addressing hyperammonemia during acute metabolic crises.
• The biochemical basis for this finding is the accumulation of specific organic acids, including 2,3-dihydroxy-2-methylbutyrate, due to the enzyme deficiency, which is then excreted in urine and can be detected through specialized metabolic testing 1.

From the Research

Isolated Increase in Urinary Excretion of 2,3 Dihydroxy-2-methylbutyrate

• An isolated increase in the urinary excretion of 2,3 dihydroxy-2-methylbutyrate is not directly mentioned in the provided studies as a specific indicator of a particular disease or condition.
• However, the studies discuss various metabolic disorders, such as Maple Syrup Urine Disease (MSUD) 2, 3, 4, and other branched-chain organic acidurias 5, which involve abnormalities in the metabolism of branched-chain amino acids.
• These disorders can lead to the accumulation of various organic acids in the urine, but 2,3 dihydroxy-2-methylbutyrate is not specifically mentioned as a key indicator.
• One study mentions the excretion of various organic acids, including alpha-methylbutyric acid, in a patient with glutaric aciduria type II 6, but this is not directly related to 2,3 dihydroxy-2-methylbutyrate.
• Without more specific information or studies directly addressing 2,3 dihydroxy-2-methylbutyrate, it is difficult to determine the exact significance of an isolated increase in its urinary excretion.

Related Metabolic Disorders

• MSUD is characterized by the accumulation of branched-chain amino acids and their corresponding keto acids in the blood and urine 2, 3, 4.
• Other branched-chain organic acidurias, such as isovaleric acidemia, propionic aciduria, and methylmalonic aciduria, also involve the accumulation of specific organic acids in the urine 5.
• These disorders can be diagnosed through the identification of specific organic acids and acylcarnitine compounds in plasma and urine using techniques like gas chromatography mass spectrometry or tandem MS-MS 5.