Pyridoxine Deficiency

Updated: Sep 15, 2016
  • Author: Richard E Frye, MD, PhD; Chief Editor: George T Griffing, MD  more...
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Overview

Background

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]

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Pathophysiology

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.

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Epidemiology

Frequency

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]

International

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

Race

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

Age

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.

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