Isolated long-chain 3-ketoacyl CoA thiolase (LCKAT) deficiency is a rare long chain fatty acid oxidation disorder (LCFAOD) that has previously been described in only 3 cases. Although these 3 patients perished before 7 weeks of age, the case of a patient who survived until the age of 13 months was recently described in Molecular Genetics and Metabolism Reports.

LCKAT is part of the mitochondrial trifunctional protein (MTP) that takes part in the last 3 steps of long chain fatty acid oxidation. The authors of the current study found biallelic mutations in the HADHB gene and, by enzyme analysis of lymphocytes and fibroblasts, encountered LCKAT deficiency with the normal activity of long chain 3-hydroxyacyl-CoA dehydrogenase, the latter also being part of the MTP.

The patient had a neonatal onset of cardiomyopathy, rhabdomyolysis, lactic acidosis, and hypoglycemia. In the newborn period, after an initial workup for sepsis and empiric antibiotic treatment without improvement, an inherited metabolic disorder was highly suspected. Thus, protein and fat were discarded from the diet, and the patient was treated with a glucose infusion plus specific therapy for hyperammonemia. 

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After being diagnosed, treated, and stabilized within the first month, the patient remained stable without complications until 4 months of age, when convulsions appeared and were later verified to be due to epilepsy. 

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Nevertheless, the central part of the patient’s complications was heart issues. “At presentation of disease, global longitudinal [left ventricular] strain was significantly decreased, suggesting the presence of impaired myocardial systolic function,” the authors wrote. 

The start of specific treatment for the disease was crucial for changing the patient’s expected outcome. This point is supported by the great improvement in heart function and carnitine levels after the initiation of treatment, which comprised low-fat formula supplemented with medium chain triglycerides and ketone body therapy with sodium-D,L-3-hydroxybutyrate.

“Importantly, within several weeks after treatment initiation, the apical sparing pattern fully disappeared and the longitudinal strain values recovered,” the authors said.

However, the case was complicated and the patient died due to heart failure at the age of 13 months. The authors noted that despite this being just the fourth reported case of LCKAT deficiency, there was a notable improvement in life expectancy. They believe this was due to early diagnosis and treatment, especially the latter with sodium-D,L-3-hydroxybutyrate.


Veenvliet ARJ, Garrelfs MR, Udink ten Cate FEA, et al. Neonatal long-chain 3-ketoacyl-CoA thiolase deficiency: clinical-biochemical phenotype, sodium-D,L-3-hydroxybutyrate treatment experience and cardiac evaluation using speckle echocardiographyMol Genet Metab Rep. 2022;31:100873. doi:10.1016/j.ymgmr.2022.100873