Pyridoxal phosphate is the active biochemical form of pyridoxine. It is a coenzyme of amino acid metabolism, particularly tryptophan and methionine. By inhibiting methionine metabolism, excessive S-adenosylmethionine accumulates, which inhibits nerve lipid and myelin synthesis. y Because tryptophan is required in the production of niacin, pyridoxine deficiency can produce a secondary niacin deficiency indistinguishable from primary pellagra. Pyridoxine is also involved in lipid and neurotransmitter synthesis. Dopamine, serotonin, epinephrine, norepinephrine, and gamma aminobutyric acid (GaBa) all require pyridoxine for their production. Lott and associates have documented reduced pyridoxal phosphate and GABA concentrations in the brain of a child dying with pyridoxine-responsive seizures. y
The recommended daily allowance of pyridoxine is 2 mg. It is found most abundantly in enriched breads, cereals and grains, chicken, orange and tomato juice, bananas, and avocados. Patients at risk for pyridoxine deficiency include those with general malnutrition, prisoners of war, refugees, alcoholics, infants of vitamin B 6 -deficient mothers, and patients using isoniazid and hydralazine. Surveys of hospitalized elderly patients have shown up that to 5 percent may have a vitamin B 6 deficiency.^] A rare autosomal recessive disorder of pyridoxine-responsive or pyridoxine-dependent neonatal seizures also exists.
Pyridoxine is unique in that both the deficiency and toxic states result in a peripheral neuropathy. Deficiency affects the blood, skin, and nervous system. The skin changes are indistinguishable from pellagra, probably due to the close interaction of niacin and pyridoxine. Pyridoxine improves the microcytic anemia of alcoholics as well as the anemia associated with pyridoxine-responsive seizures in infants. Pyridoxine-deficient peripheral neuropathy is seen primarily in patients on isoniazid or hydralazine, and it is characterized by sensory loss in distal limbs, weakness, and reflex changes. Patients describe burning feet and painful paresthesias.
Figure 40-8 (Figure Not Available) Vitamin E deficiency myelopathy. Cross section of cervical spinal cord. The triple arrowheads denote light-staining symmetrical areas of degeneration involving the posterior columns. The two single arrowheads indicate involvement of the dorsal and ventral spinocerebellar tracts. In the posterior columns, the fasciculus cuneatus is affected to a greater extent than the gracilis. Microscopically, numerous swollen and dystrophic axons (spheroids) and astrocytosis are present in the posterior columns, and nerve cell loss is seen in the dorsal root ganglia (luxol-fast blue-periodic acid-SchFrom Rosenblum JL, Keating JP, Prensky AL, Nelson JS: A progressive neurologic syndrome in children with chronic liver disease. N Engl J Med 1981;304:506.)
CNS manifestations include depression, irritability, and confusion. y Infants born to pyridoxine-deficient mothers may develop neonatal seizures y as part of their vitamin deficiency state, a condition distinct from hereditary pyridoxine-responsive seizures. Up to 10 percent of patients who are on isoniazid and have tuberculosis may develop a peripheral sensory neuropathy. Isoniazid promotes increased pyridoxine excretion in the urine, resulting in a deficiency state. Similar changes are seen in patients on hydralazine.
Excess pyridoxine also results in a peripheral neuropathy. Megadoses of pyridoxine produce a sensory neuropathy, generally in excess of 2 g/day but has been reported with longstanding use of as little as 200 mg/day. y , y Symptoms of paresthesias, ataxia, and burning feet occur 1 month to 3 years after starting pyridoxine. Sural nerve biopsies show reduced myelin fiber density and myelin debris, suggesting axonal degeneration. After stopping pyridoxine, all patients improve, but the condition resolves entirely in only a few. Contrary to claims in the lay press, such cases demonstrate that not all B vitamins, even though they are water soluble and are excreted in the urine, are benign when taken in megadoses.
Urinary assays for xanthurenic acid and other pyridoxine metabolites may be performed following tryptophan loading in patients suspected of having pyridoxine deficiency. In the serum, cystathionine levels may also be elevated in this condition.
Daily intake of vitamin B6 (150 to 450 mg) prevents the neuropathy of isoniazid and should be used by patients on this drug. Once it is established, the neuropathy does not entirely resolve but may improve with replacement vitamin B6 .
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