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Pyridoxine Deficiency

  • Author: Richard E Frye, MD, PhD; Chief Editor: George T Griffing, MD  more...
Updated: Jan 15, 2014


Pyridoxine 5'-phosphate, vitamin B-6, is an essential cofactor in various transamination, decarboxylation, glycogen hydrolysis, and synthesis pathways involving carbohydrate, sphingolipid, amino acid, heme, and neurotransmitter metabolism. Pyridoxine deficiency causes blood, skin, and nerve changes. This vitamin is unique in that either deficiency or excess can cause peripheral neuropathy.[1, 2, 3, 4, 5]



After absorption, pyridoxine, pyridoxamine, and pyridoxal are transported into hepatic cells by facilitated diffusion. Pyridoxal kinase phosphorylates pyridoxine and pyridoxamine, after which they are converted to pyridoxal 5'-phosphate (PLP) by a flavin-dependent enzyme. PLP either remains in the hepatocyte, where it is bound to an apoenzyme, or it is released into the serum, where it is tightly bound to albumin. Free pyridoxal is degraded by alkaline phosphatase, hepatic and renal aldehyde oxidases, and pyridoxal dehydrogenase.

Pyridoxine 5'-phosphate is an essential cofactor in various transamination, decarboxylation, and synthesis pathways involving carbohydrates, sphingolipids, sulfur-containing amino acids, heme, and neurotransmitters. PLP is a coenzyme of tryptophan, methionine, and gamma aminobutyric acid (GABA) metabolism. With methionine deficiency, S -adenosylmethionine accumulates, resulting in the inhibition of sphingolipid and myelin synthesis. Tryptophan is a precursor to several neurotransmitters and is required for niacin production. Thus, pyridoxine deficiency can cause a syndrome indistinguishable from pellagra. PLP is a cofactor for glutamic acid decarboxylase, the enzyme that produces GABA, such that PLP deficiency results in insufficient GABA. Since GABA is the major inhibitor cortical neurotransmitter, PLP deficiency can lead to seizures. Interestingly, pyridoxine-dependent seizures are not caused by a pyridoxine deficiency per se but rather due to an increased depletion of PLP.

The neurotransmitters dopamine, serotonin, epinephrine, norepinephrine, glycine, glutamate, and GABA also require PLP for their production. Homocystine metabolism is dependent on pyridoxine, and high homocystine levels can result from pyridoxine deficiency.




United States

Idiopathic pyridoxine deficiency is very rare. Acquired deficiency is associated with inflammatory disorders and with concurrent use of several medications.[6, 7] Inherited pyridoxine-dependent seizure is a rare autosomal-recessive condition.[8, 9, 10, 11] Pyridoxine-responsive sideroblastic anemia is also rare.[12]


Malnutrition or a diet limited to unenriched grains increases the risk for developing pyridoxine deficiency.


Chinese women of childbearing age have an increased risk of developing pyridoxine deficiency.


Although pyridoxine deficiency can develop in persons of any age, elderly persons are at increased risk.[12, 13]

Pyridoxine-dependent seizures occur almost exclusively in children younger than 3 months, usually presenting in the newborn period.[8, 9, 10]

Hereditary sideroblastic anemia usually manifests within the first few years of life.

Contributor Information and Disclosures

Richard E Frye, MD, PhD Associate Professor, Department of Pediatrics, University of Arkansas for Medical Sciences

Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, International Neuropsychological Society, American Academy of Pediatrics

Disclosure: Nothing to disclose.


Serge A Jabbour, MD, FACP, FACE Professor of Medicine, Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson Medical College of Thomas Jefferson University

Serge A Jabbour, MD, FACP, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Medical Association, American Thyroid Association, Endocrine Society, Pennsylvania Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society

Disclosure: Nothing to disclose.

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