eMedicine Specialties > Endocrinology > Metabolic Disorders

Pyridoxine Deficiency

Author: Richard E Frye, MD, PhD, Assistant Professor, Departments of Pediatrics and Neurology, University of Texas Health Science Center at Houston
Coauthor(s): Serge A Jabbour, MD, Associate Professor, Department of Medicine, Division of Endocrinology, Thomas Jefferson University
Contributor Information and Disclosures

Updated: Dec 8, 2008

Introduction

Background

Pyridoxine 5'-phosphate 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

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

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 Pyridoxine-responsive sideroblastic anemia is also rare.11

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.11,12
  • 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.

Clinical

History

  • Factors that increase the risk for pyridoxine deficiency11
  • Other patient history
    • Sideroblastic anemia
    • Pregnancy - Pregnancy can cause a pyridoxine-deficient state; however, a change in the ratio of plasma PLP to pyridoxal does occur, thereby falsely suggesting a deficiency state if only serum PLP is measured.
    • Physical exercise - This may transiently increase plasma PLP levels.
  • Symptoms and conditions associated with low pyridoxine levels
    • General
      • Weakness
      • Dizziness
      • Inflammation6,7
    • Cardiovascular
      • Atherosclerosis
      • Early myocardial infarction
      • Early stroke7
      • Recurrent venous thromboembolism
    • Hematologic - Fatigue resulting from anemia is an example.
    • Peripheral nervous system
      • Bilateral, distal limb numbness (appears early)
      • Bilateral, distal limb burning paresthesia (replaces numbness later in the course)
      • Distal limb weakness (rare)
    • Central nervous system (CNS)
      • Depression
      • Irritability
      • Confusion
      • Generalized seizures
      • White matter lesions
    • Gastrointestinal
      • Anorexia
      • Vomiting
  • Symptoms and conditions associated with secondary niacin deficiency (ie, pellagra)
    • Skin
      • Erythematous itching and burning
      • Blisters and vesicles
      • Hyperpigmentation and thickening
    • CNS
      • Depression
      • Anxiety
      • Irritability
      • Disorientation
      • Stupor
      • Coma
    • Gastrointestinal
      • Anorexia
      • Nausea
      • Abdominal discomfort and pain
      • Glossitis
      • Diarrhea

Physical

  • Oral
    • Glossitis
    • Cheilosis
  • Dermatologic - Seborrheic dermatitis is an example.
  • Adult, neurologic
    • Distal limb numbness and weakness
    • Impaired vibration and proprioception
    • Preserved pain and temperature
    • Sensory ataxia
    • Generalized seizures
  • Neonatal and young infant, neurologic
    • Hypotonia
    • Irritability
    • Restlessness
    • Focal, bilateral motor, or myoclonic seizures
    • Infantile spasms
  • Secondary niacin deficiency
    • Skin
      • Dermatitis over sun-exposed areas
      • Blisters and vesicles
      • Beefy red, raw tongue
    • CNS
      • Confusion
      • Dementia
      • Disorientation
      • Rigid tone
      • Primitive reflexes

Causes

  • Pyridoxine intake is reduced in cases of severe malnutrition.
  • Pyridoxine absorption is reduced in elderly persons and in patients with intestinal disease or who have undergone surgery.
  • Pyridoxine clearance is enhanced by liver disorders, such as hepatitis, and by several medications.
  • Pyridoxine breakdown is enhanced in conditions associated with increased alkaline phosphatase levels.
  • Hematologic pathway enzymes with a low affinity for pyridoxine cause a microcytic-hypochromic pyridoxine-responsive anemia (ie, sideroblastic anemia). An X-linked inherited condition is observed in carrier females and affected males. An autosomal form of this disorder has been reported in a single family. Long-term alcohol ingestion and iatrogenically induced deficiencies can also result in this type of anemia.
  • Hydrazones from isoniazid and certain mushrooms bind PLP to form isoniazid-hydrazone complexes, resulting in decreased pyridoxal availability for use in other reactions.
  • CNS glutamic acid decarboxylase with a low affinity for pyridoxine results in pyridoxine-dependent seizures by causing low GABA and high glutamate levels.
  • Low maternal pyridoxine levels can cause pyridoxine-responsive seizures.11
  • Excessive maternal pyridoxine supplementation can induce pyridoxine turnover, resulting in a higher requirement. Pyridoxine-responsive seizures may result.
  • Endogenous or exogenous estrogens can alter tryptophan metabolism by directly inhibiting kynureninase, a proximal, potentially rate-limiting enzyme in tryptophan metabolism. A pyridoxine-dependent compound, kynureninase is the same enzyme that is inhibited in the pyridoxine-deficient state. Altered tryptophan metabolism resulting from high estrogen levels may be attributed to a pyridoxine deficiency if the former is not considered.

More on Pyridoxine Deficiency

Overview: Pyridoxine Deficiency
Differential Diagnoses & Workup: Pyridoxine Deficiency
Treatment & Medication: Pyridoxine Deficiency
Follow-up: Pyridoxine Deficiency
References
Further Reading
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References

  1. Bender DA. Vitamin B6 requirements and recommendations. Eur J Clin Nutr. May 1989;43(5):289-309. [Medline].

  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. In: 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. In: 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. Jan 2004;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. Oct 14 2008;[Medline].

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

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

  11. Morris MS, Picciano MF, Jacques PF, et al. Plasma pyridoxal 5'-phosphate in the US population: the National Health and Nutrition Examination Survey, 2003-2004. Am J Clin Nutr. May 2008;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. Mar 2008;108(3):443-53; discussion 454. [Medline].

  13. Baggot PJ, Eliseo AJ, DeNicola NG, et al. Pyridoxine-related metabolite concentrations in normal and Down syndrome amniotic fluid. Fetal Diagn Ther. 2008;23(4):254-7. [Medline].

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

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Further Reading

Related eMedicine topic:
 Vitamin B-6 Dependency Syndromes

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Keywords

pyridoxine deficiency, vitamin deficiency, vitamin B, vitamin B6, pyridoxine, vitamin B deficiency, pyridoxine 5'-phosphate, pyridoxal 5'-phosphate, PLP, vitamin B-6 deficiency, malnutrition, peripheral neuropathy, poor diet, pyridoxine-dependent seizures, hereditary sideroblastic anemia, cirrhosis, hemodialysis, peritoneal dialysis, chronic renal failure, homocystinuria, homocystinemia, Gyromitra poisoning, mushroom poisoning, fungus toxicity, mushroom toxicity

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Contributor Information and Disclosures

Author

Richard E Frye, MD, PhD, Assistant Professor, Departments of Pediatrics and Neurology, University of Texas Health Science Center at Houston
Richard E Frye, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society, and International Neuropsychological Society
Disclosure: Nothing to disclose.

Coauthor(s)

Serge A Jabbour, MD, Associate Professor, Department of Medicine, Division of Endocrinology, Thomas Jefferson University
Serge A Jabbour, MD 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, and Pennsylvania Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Elena Citkowitz, MD, PhD, FACP, Clinical Professor of Medicine, Yale University School of Medicine; Director, Cholesterol Management Center, Director, Cardiac Rehabilitation, Department of Medicine, Hospital of St Raphael
Elena Citkowitz, MD, PhD, FACP is a member of the following medical societies: American College of Physicians, American Heart Association, National Lipid Association, and Sigma Xi
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Kent Wehmeier, MD, Professor, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, St Louis University School of Medicine
Kent Wehmeier, MD is a member of the following medical societies: American Society of Hypertension, Endocrine Society, and International Society for Clinical Densitometry
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor 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, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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