Neuropathy might be responsive to dietary interventions at a very early stage of the disease in patients with mitochondrial trifunctional protein (TFP) deficiency, a type of long chain fatty acid oxidation disorder (LCFAOD), according to a new study published in JIMD Reports

A common complication in patients with TFP deficiency and long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, another type of LCFAOD, is axonal peripheral neuropathy, and current treatment approaches cannot prevent this in most patients. 

Here, a team of researchers from the Faculty of Medicine at the University of Freiburg in Germany led by Ute Spiekerkoetter, MD, reported the cases of 3 sisters with TFP deficiency. The sisters did not receive any treatment until they were adolescents. At that point, they were diagnosed with isolated axonal sensory neuropathy following electrophysiological studies. 

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All 3 girls were clinically asymptomatic, with only mild exercise intolerance and a lack of deep tendon reflexes in the legs.

Read more about the complications of LCFAOD

They were managed with a reduced-fat and modified-fat diet. Their overnight fasting time was also shortened. This led to the complete normalization of the electrophysiological findings after a year.

“Further studies are needed to elucidate the pathophysiological factors contributing to the axonal damage and identify possible treatment targets,” the authors of the study wrote.

LCFAOD is a group of rare genetic disorders characterized by the inability of the body to break down long-chain fatty acids. There are several enzymes that are essential for long-chain fatty acid metabolism, and the disease can be caused by a mutation in a gene encoding any of these enzymes.

The accumulation of long-chain fatty acids leads to symptoms such as rhabdomyolysis, hypotonia, muscle weakness, and exercise intolerance. Disease management can be achieved through a strict nutritional plan consisting of a diet low in long-chain fatty acids supplemented with medium-chain triglycerides.


Grünert SC, Eckenweiler M, Spiekerkoetter U. Reversible sensory neuropathy in mitochondrial trifunctional protein deficiency. JIMD Rep. 2022;63(3):207-210. doi:10.1002/jmd2.12279