Cause:Pyridoxine-deficient type is genetic. Responsive/not deficient type is genetic, x-linked; drugs like INH induce it by complexing with pyridoxine
Pathophys:Pyridoxine is necessary for tryptophan, 5-HIAA, alanine, nicotinic acid, and ALA synthetase synthesis, as well as mitochondrial Fe use. In deficient type, unknown reason for increased requirements, but the problem fully corrects on low-dose replacement. In responsive/not deficient type, the problem never fully corrects; perhaps the defect is distal to pyridoxine and a large load partially overdrives the reaction
Sx:Deficient type: peripheral neuropathy
Si:
Deficient type: Anemia
Responsive/not deficient type: hepatosplenomegaly, anemia
Deficient type: Corrects with low dose (5 mg/d); reverts in 2-3 mo if rx stopped
Responsive/not deficient type: partially corrects with high dose (300 mg/d)
Lab:
Chem:Fe and TIBC levels elevated
Hem:Normal rbc survival, hypochromic anemia in both types. Reticulocytes normal or increased in deficient type; low in responsive/not deficient type
Path:Marrow shows ring sideroblasts (normoblasts with Fe free in mitochondria), r/o idiopathic, myelodysplastic (Nejm 1999;340:1649), or alcohol-induced anemias (Nejm 1976;295:881)
Urine:Xanthurenic acid with tryptophan load is normal in deficient type but increased in responsive/not deficient type. Porphyrins increased in deficient type; decreased in responsive/not deficient type