MCKAT Deficiency

Introduction

Medium chain 3-ketoacyl-CoA thiolase deficiency (MCKAT) is the rarest of the fatty acid oxidation disorders (FAODs). If you know someone who is diagnosed with this disorder, it can be overwhelming, and you may feel lost. At the International Network for Fatty Acid Oxidation Research and Management (INFORM), we want to help. Alongside our founder, Jerry Vockley, we want to provide you with more information on FAODs to help you better understand this deficiency.

What is MCKAT Deficiency?

Medium chain 3-ketoacyl-CoA thiolase deficiency (MCKAT), the rarest of the many fatty acid oxidation disorders, is a defect in the cellular pathway for breaking down fats. The breakdown of fats takes place in the mitochondria that act as the “powerhouses of the cells.”  When there are MCKAT defects, the last step in the final round of the breakdown of fats is reduced or missing completely. Recent fatty acid oxidation research has shown that this step is an important controller of the rate of fat entry into the fat breakdown pathways.

Signs and Symptoms

Because only a few cases of MCKAT have been identified to date, there is limited knowledge about the signs and symptoms of this disorder. In the first reported case, a 2-day-old infant showed signs of:

  • Vomiting
  • Dehydration
  • Acidic blood (metabolic acidosis)
  • Liver disease
  • Severe muscle breakdown (rhabdomyolysis)
  • Reddish-brown urine (myoglobinuria)

Later patients have shown other symptoms, including:

  • Low blood sugar (hypoglycemia)
  • Vomiting
  • Floppiness (poor muscle tone)
  • Coma if the time between feedings is too long (fasting intolerance)
  • Heart malfunctions (cardiomyopathy)

In one extreme case, the first presentation was sudden death (SIDS).

How to Diagnose MCKAT Deficiency

The only extensive diagnostic reports on MCKAT were taken from the first case of the 2-day old infant. Organic acid analysis of urine revealed elevated lactic acids, ketones, and significantly increased dicarboxylic acids. In skin cells, certain fats made little energy. There was also little medium-chain 3-ketoacyl-CoA thiolase (MCKAT) activity and reduced MCKAT protein. No additional diagnostic information is available at this time.

Treatment

Unfortunately, there are no treatments available because of the limited patient experience; however, individuals with symptoms such as dehydration, low blood sugar, and heart malfunctions should be treated with the appropriate therapies immediately. They could be suffering from one of the many fatty oxidation disorders.

Investigational Therapies and Fatty Acid Oxidation Research

Information on current clinical trials is posted at ClincalTrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

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