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Pyridoxine Deficiency

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

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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Contributor Information and Disclosures
Author

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.

Coauthor(s)

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.

References
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  2. Tierney LM, McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis and Treatment. 40th ed. New York, NY: McGraw-Hill; 2001.

  3. Goetz CG. Vitamin deficiencies. Goetz CG, Pappert EJ, eds. Textbook of Clinical Neurology. Philadelphia, Pa: WB Saunders; 1999.

  4. Scriver CR, Gibson KM. Disorders of beta- and gamma-amino acids in free and peptide-linked forms. Scriver CR, Beaudet A, Sly W, et al, eds. The Metabolic Basis of Inherited Disease. 7th ed. New York, NY: McGraw-Hill; 1995. 1349-68.

  5. Beutler E, Lichtman MA, Coller BS, eds. Williams Hematology. 6th ed. New York, NY: McGraw-Hill; 2001.

  6. Chiang EP, Smith DE, Selhub J, et al. Inflammation causes tissue-specific depletion of vitamin B6. Arthritis Res Ther. 2005. 7(6):R1254-62. [Medline]. [Full Text].

  7. Kelly PJ, Kistler JP, Shih VE, et al. Inflammation, homocysteine, and vitamin B6 status after ischemic stroke. Stroke. 2004 Jan. 35(1):12-5. [Medline]. [Full Text].

  8. Kaczorowska M, Kmiec T, Jakobs C, et al. Pyridoxine-dependent seizures caused by alpha amino adipic semialdehyde dehydrogenase deficiency: the first Polish case with confirmed biochemical and molecular pathology. J Child Neurol. 2008 Oct 14. [Medline].

  9. Striano P, Battaglia S, Giordano L, et al. Two novel ALDH7A1 (antiquitin) splicing mutations associated with pyridoxine-dependent seizures. Epilepsia. 2008 Aug 19. [Medline].

  10. Khayat M, Korman SH, Frankel P, et al. PNPO deficiency: an under diagnosed inborn error of pyridoxine metabolism. Mol Genet Metab. 2008 Aug. 94(4):431-4. [Medline].

  11. Morris MS, Picciano MF, Jacques PF, Selhub J. Plasma pyridoxal 5'-phosphate in the US population: the National Health and Nutrition Examination Survey, 2003-2004. Am J Clin Nutr. 2008 May. 87(5):1446-54. [Medline].

  12. Woolf K, Manore MM. Elevated plasma homocysteine and low vitamin B-6 status in nonsupplementing older women with rheumatoid arthritis. J Am Diet Assoc. 2008 Mar. 108(3):443-53; discussion 454. [Medline].

  13. Baggot PJ, Eliseo AJ, DeNicola NG, Kalamarides JA, Shoemaker JD. Pyridoxine-related metabolite concentrations in normal and Down syndrome amniotic fluid. Fetal Diagn Ther. 2008. 23(4):254-7. [Medline]. [Full Text].

  14. Balasa VV, Kalinyak KA, Bean JA, Stroop D, Gruppo RA. Hyperhomocysteinemia is associated with low plasma pyridoxine levels in children with sickle cell disease. J Pediatr Hematol Oncol. 2002 Jun-Jul. 24(5):374-9. [Medline].

  15. Camaschella C. Recent advances in the understanding of inherited sideroblastic anaemia. Br J Haematol. 2008 Oct. 143(1):27-38. [Medline].

  16. Stockler S, Plecko B, Gospe SM Jr, et al. Pyridoxine dependent epilepsy and antiquitin deficiency: clinical and molecular characteristics and recommendations for diagnosis, treatment and follow-up. Mol Genet Metab. 2011 Sep-Oct. 104(1-2):48-60. [Medline].

  17. Huang SC, Wei JC, Lin PT, Wu DJ, Huang YC. Plasma pyridoxal 5'-phosphate is not associated with inflammatory and immune responses after adjusting for serum albumin in patients with rheumatoid arthritis: a preliminary study. Ann Nutr Metab. 2012. 60(2):83-9. [Medline].

  18. van Karnebeek CD, Hartmann H, Jaggumantri S, et al. Lysine restricted diet for pyridoxine-dependent epilepsy: First evidence and future trials. Mol Genet Metab. 2012 Nov. 107(3):335-44. [Medline].

 
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