Can elevated 2,3 dihydroxy-2-methylbutyrate (organic acid) levels cause swollen red hands and feet?

From the Guidelines

Elevated levels of 2,3-dihydroxy-2-methylbutyrate are not typically associated with swollen red hands and feet as a direct symptom. This organic acid is a metabolite that can be elevated in certain inborn errors of metabolism, particularly in disorders affecting branched-chain amino acid metabolism such as 3-OH-Isobutyryl-CoA hydrolase deficiency or Short-chain enoyl-CoA hydratase deficiency, as indicated in a study published in Genetics in Medicine 1. The primary symptoms of these metabolic disorders usually include neurological issues, developmental delays, feeding difficulties, and in severe cases, metabolic acidosis or ketosis. Swollen red extremities, known medically as acrodermatitis or erythema, are more commonly associated with other conditions like inflammatory disorders, allergic reactions, or certain infections.

Key Points to Consider

• Elevated 2,3-dihydroxy-2-methylbutyrate levels are associated with specific inborn errors of metabolism, as outlined in a technical standard by the American College of Medical Genetics and Genomics (ACMG) 1.
• The symptoms of these metabolic disorders do not typically include swollen red hands and feet.
• If you're experiencing swollen red hands and feet along with elevated 2,3-dihydroxy-2-methylbutyrate levels, it's essential to consult with a metabolic specialist or geneticist to determine the underlying cause of both the biochemical abnormality and the physical symptoms.
• Additional testing, such as comprehensive metabolic panels, complete blood counts, or genetic testing, may be recommended to evaluate the relationship between the elevated organic acid levels and the physical symptoms. Some possible disorders that may be identified through abnormal urine organic acid analysis include:
• Classic organic acidemias due to inborn errors of amino acid metabolism
• Disorders of the urea cycle
• Fatty acid oxidation disorders
• Energy metabolism disorders
• Purine and pyrimidine metabolism disorders
• Neurotransmission disorders
• Others, as discussed in the study published in Genetics in Medicine 1.

From the Research

Swollen Red Hands and Feet

• The question of whether elevated 2,3 dihydroxy-2-methylbutyrate (organic acid) levels can cause swollen red hands and feet is complex and requires an understanding of the underlying biochemical processes.
• Studies have shown that disorders affecting isoleucine catabolism, such as beta-ketothiolase deficiency and 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency, can lead to the accumulation of 2-methyl-3-hydroxybutyrate and other organic acids 2, 3.
• However, these studies do not directly address the question of whether elevated 2,3 dihydroxy-2-methylbutyrate levels can cause swollen red hands and feet.
• One study reports a case of a patient with Raynaud's phenomenon who developed a possible erythromelalgia-like syndrome, characterized by burning pain, increased skin temperature, and erythema of the extremities, after taking nifedipine 4.
• While this study does not involve 2,3 dihydroxy-2-methylbutyrate, it suggests that certain conditions can cause symptoms similar to swollen red hands and feet.
• There is no direct evidence in the provided studies to suggest that elevated 2,3 dihydroxy-2-methylbutyrate levels can cause swollen red hands and feet 2, 3, 5, 6.