Morton's foot and pyridoxal 5'-phosphate deficiency: genetically linked traits

Med Hypotheses. 2014 Dec;83(6):644-8. doi: 10.1016/j.mehy.2014.09.003. Epub 2014 Sep 16.


Vitamin B6 is an essential vitamin needed for many chemical reactions in the human body. It exists as several vitamins forms but pyridoxal 5'-phosphate (PLP) is the phosphorylated form needed for transamination, deamination, and decarboxylation. PLP is important in the production of neurotransmitters, acts as a Schiff base and is essential in the metabolism of homocysteine, a toxic amino acid involved in cardiovascular disease, stroke, thrombotic and Alzheimer's disease. This report announces the connection between a deficit of PLP with a genetically linked physical foot form known as the Morton's foot. Morton's foot has been associated with fibromyalgia/myofascial pain syndrome. Another gene mutation methylenetetrahydrofolate reductase (MTHFr) is now being recognized much commonly than previous with chronic fatigue, chronic Lyme diseases and as "the missing link" in other chronic diseases. PLP deficiency also plays a role in impaired glucose tolerance and may play a much bigger role in the obesity, diabetes, fatty liver and metabolic syndrome. Without the Schiff-base of PLP acting as an electron sink, storing electrons and dispensing them in the mitochondria, free radical damage occurs! The recognition that a phenotypical expression (Morton's foot) of a gene resulting in deficiency of an important cofactor enzyme pyridoxal 5'-phosphate will hopefully alert physicians and nutritionist to these phenomena. Supplementation with PLP, L5-MTHF, B12 and trimethylglycine should be used in those patients with hyperhomocysteinemia and/or MTHFR gene mutation.

MeSH terms

  • Fibromyalgia / genetics
  • Foot Deformities / genetics*
  • Humans
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics
  • Mitochondria / metabolism
  • Mutation
  • Myofascial Pain Syndromes / genetics*
  • Myofascial Pain Syndromes / metabolism
  • Myofascial Pain Syndromes / therapy
  • Neurotransmitter Agents / metabolism
  • Phenotype
  • Pyridoxal Phosphate / deficiency*
  • Pyridoxal Phosphate / genetics
  • Schiff Bases / metabolism
  • Vitamin B 12 / metabolism


  • Neurotransmitter Agents
  • Schiff Bases
  • Pyridoxal Phosphate
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Vitamin B 12