MCKAT Deficiency

Introduction

Medium chain 3-ketoacyl-CoA thiolase deficiency (MCKAT) is the rarest of the many defects in the cellular pathway for breaking down fats. The breakdown of fats takes place in the mitochondria, called the “powerhouses of the cells.”  In MCKAT defects, the last step in the final round of the breakdown of fats is reduced or missing. Recent laboratory studies have 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 was vomiting, with other serious symptoms, including dehydration, acidic blood (metabolic acidosis), liver disease, and severe muscle breakdown (rhabdomyolysis) resulting in reddish-brown urine (myoglobinuria). Later patients have shown other symptoms, including low blood sugar (hypoglycemia), vomiting, floppiness (poor muscle tone), and even coma whenever the time between feedings is too long (fasting intolerance).  Others have had heart malfunctions (cardiomyopathy), and, in one case, the first presentation was with sudden death (SIDS).

Diagnosis

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

Treatment

No treatments for MCKAT are 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.

Investigational Therapies

Information on current clinical trials is posted at www.clinicaltrials.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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