History

Contributing factors

Several factors contribute to an increased risk for pyridoxine deficiency,^[15]as follows:

Advanced age
Medical conditions that may increase the risk for pyridoxine deficiency include the following:
- Severe malnutrition
- Sickle cell disease
- Inflammatory conditions^{[10, 11]}
- Rheumatoid arthritis^[10]
- Hospitalization
- Celiac disease
- Hepatitis and extrahepatic biliary obstruction
- Hepatocellular carcinoma
- Chronic renal failure
- Kidney transplant^[18]
- Hyperoxaluria types I and II
- High serum alkaline phosphatase level, such as in cirrhosis and tissue injury
- Catabolic state
Medical procedures that may increase the risk for pyridoxine deficiency include the following:
- Hemodialysis
- Peritoneal dialysis
- Phototherapy for hyperbilirubinemia
Medications that may increase the risk for pyridoxine deficiency include the following:
- Cycloserine
- Hydralazine
- Isoniazid
- D-penicillamine
- Pyrazinamide
Social-behavioral conditions that may increase the risk for pyridoxine deficiency include the following:
- Excessive alcohol ingestion (except for pyridoxine-supplemented beer)
- Tobacco smoking
- Severe malnutrition
Other risk factors that may increase the risk for pyridoxine deficiency include the following:
- Poisoning, such as Gyromitra mushroom poisoning
- Perinatal factors, such as a pyridoxine-deficient mother
- Inherited conditions, such as pyridoxine-dependent neonatal seizures^{[12, 13, 14]}

Other patient history

A patient's medical history may include the following:

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

Symptoms and conditions associated with low pyridoxine levels include the following:

General
- Weakness
- Dizziness
- Inflammation^{[10, 11]}
Cardiovascular
- Atherosclerosis
- Early myocardial infarction
- Early stroke^[11]
- 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)

Symptoms and conditions associated with secondary niacin deficiency (ie, pellagra) include the following:

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 Examination

Physical examination findings may include the following:

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

Differential Diagnoses

Bender DA. Vitamin B6 requirements and recommendations. Eur J Clin Nutr. 1989 May. 43(5):289-309. [QxMD MEDLINE Link].
Tierney LM, McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis and Treatment. 40th ed. New York, NY: McGraw-Hill; 2001.
Goetz CG. Vitamin deficiencies. Goetz CG, Pappert EJ, eds. Textbook of Clinical Neurology. Philadelphia, Pa: WB Saunders; 1999.
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.
Beutler E, Lichtman MA, Coller BS, eds. Williams Hematology. 6th ed. New York, NY: McGraw-Hill; 2001.
Camaschella C. Recent advances in the understanding of inherited sideroblastic anaemia. Br J Haematol. 2008 Oct. 143(1):27-38. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
[Guideline] Coughlin CR 2nd, Tseng LA, Abdenur JE, et al. Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency. J Inherit Metab Dis. 2021 Jan. 44 (1):178-92. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Chiang EP, Smith DE, Selhub J, et al. Inflammation causes tissue-specific depletion of vitamin B6. Arthritis Res Ther. 2005. 7(6):R1254-62. [QxMD MEDLINE Link]. [Full Text].
Kelly PJ, Kistler JP, Shih VE, et al. Inflammation, homocysteine, and vitamin B6 status after ischemic stroke. Stroke. 2004 Jan. 35(1):12-5. [QxMD MEDLINE Link]. [Full Text].
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 Dec. 23(12):1455-9. [QxMD MEDLINE Link].
Striano P, Battaglia S, Giordano L, et al. Two novel ALDH7A1 (antiquitin) splicing mutations associated with pyridoxine-dependent seizures. Epilepsia. 2009 Apr. 50(4):933-6. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link]. [Full Text].
Meyer HE, Willett WC, Fung TT, Holvik K, Feskanich D. Association of high intakes of vitamins B6 and B12 from food and supplements with risk of hip fracture among postmenopausal women in the Nurses' Health Study. JAMA Netw Open. 2019 May 3. 2 (5):e193591. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].