Pyridoxine-responsive convulsion

AASA dehydrogenase deficiency (pyridoxine-responsive convulsions). 

Isoniazid is bactericidal for growing tubercle bacilli, is absorbed orally, and is metabolized by acetylation. It is a structural analogue of pyridoxine and may cause pyridoxine deficiency, peripheral neuritis and, in toxic doses, pyridoxine-responsive convulsions. Its mechanism of action is not known. 

It is indicated to prevent and treat isoniazid, hydralazine, penicillamine and cycloserine induced neurological disturbances, mental symptoms in women on oral contraceptives, pyridoxine responsive anaemia and homocystinuria, morning sickness and hyperemesis gravidarum, convulsions in infants and children. 

About half of individuals who do not respond to pyridoxine will sustain ectopia lentisbj age 5-10 years. Indeed, the diagnosis commonly is made by an ophthalmologist. The median IQ score for B6 responsive and nonresponsive patients is 78 and 56 respectively. Some children present at 1-2 years with psychomotor retardation, convulsions (=20% of cases) and psychiatric difficulties such as depression and personality disorders (=50% of cases). 

There are several vitamin Bg-responsive inborn errors of metabolism that include (1) cases of infantile convulsions in which the apoenzyme for glutamate decarboxylase has a poor affinity for the coenzyme (2) a type of chronic anemia in which the number but not morphological abnormality of erythrocytes is improved by pyridoxine supplementation (3) xanthurenic aciduria in which affinity of the mutant kynureninase for PLP is decreased (4) primary cystathion-inuria caused by similarly defective cystathionase and (5) homocystinuria in which there is less of the normal cystathionine synthetase. In these cases increased levels (200 to lOOOmg/day) of administered vitamin Bg are required for life. Low vitamin Bg status (together with low vitamin B12 and folate status) in humans has been linked to hyperho-mocysteinemia and as an independent risk factor for cardiovascular disease. ... 

Although it is possible to describe the clinicopatho-logical manifestations of pyridoxine deficiency and the metabolic role of pyridoxal phosphate, each pathological alteration cannot be explained by a specific metabolic alteration. Deficiency of a vitamin involved in several steps of the intermediary metabolism of amino acids is bound to be associated with severe clinicopath-ological changes, but the specific metabolic alterations responsible for the anemia and convulsions in pyridoxine deficiency have not been identified. y-Amino butyric acid, cystathione, sphingosine, and 5-hydroxy-tryptamine are compounds abundant in the brain. Pyridoxal phosphate is involved in their metabolic formation. Is there any correlation between the role of pyridoxal phosphate in the metabolism of these compounds and the development of convulsions and ataxia in pyridoxine deficiency Is the role of pyridoxine phosphate in the intermediary metabolism of sulfur amino acid related to the development of seborrheic dermatitis ... 

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