Vitamin dependency syndromes

Marginal inadequacy, affecting amino acid metabolism and possibly also steroid hormone responsiveness, may be relatively common. A number of vitamin Be dependency syndromes have been reported - inborn errors of metabolism in which the defect is in the coenzyme binding site of the affected enzyme. 

A small number of patients show one or the other of the biochemical signs associated with vitamin Be deficiency despite apparendy adequate status, and require high intakes of the vitamin to normalize the abnormal metabolic marker. These are genetic diseases and have been termed vitamin Be dependency syndromes. 

The molecular basis of the other vitamin Be dependency syndromes is a severely reduced affinity of the defective enzyme for its cofactor, and the patients respond well to doses of 50 to 1,000 mg of vitamin Be per day. Apart from the affected enzyme, other biochemical indices of vitamin Be nutritional status are normal in these patients (Frimpter et al., 1969 Mudd, 1971). 

Frimpter GW, Andelman RJ, and George WF (1969) Vitamin Be -dependency syndromes. New horizons in nutrition. American Journal of Clinical Nutrition 22,794-805. 

The nausea and vomiting associated with the first trimester of pregnancy are benign and self-limiting in nature. If at all possible, no medications should be used. If absolutely necessary, antihistaminics (meclizine and trimethobenzamide) may be effective. Pyridoxine (vitamin Bg) should not be prescribed, as it may predispose the infant to vitamin Bg-dependent syndrome. 

Pyridoxine, a water-soluble vitamin, is used in dietary vitamin Bg deficiency, seizures related to vitamin Bg deficiency or dependency, vitamin Bg-responsive anemias or dependency syndrome (inborn errors of metabolism), prevention of vitamin Bg deficiency during isoniazid therapy, and treatment of vitamin Bg deficiency secondary to isoniazid. 

Treatment of pregnant women with warfarin can lead to fetal bone abnormalities (fetal warfarin syndrome). Two proteins are present in bone that contain y-carboxygluta-mate, osteocalcin and bone matrix Gla protein. Osteocalcin also contains hydroxyproHne, so its synthesis is dependent on both vitamins K and C in addition, its synthesis is induced by vitamin D. The release into the circulation of osteocalcin provides an index of vitamin D stams. 

Abuse/Dependency Chronic use of laxatives, particularly stimulants, may lead to laxative dependency, which in turn may result in fluid and electrolyte imbalances, steatorrhea, osteomalacia, vitamin and mineral deficiencies, and a poorly functioning colon. Also known as laxative abuse syndrome (LAS), it is difficult to diagnose. Cathartic colon Cathartic colon, a poorly functioning colon, results from the chronic abuse of stimulant cathartics. 

Hypoprothrombinemia may occur in malabsorption syndromes and also the use of broad-spectrum antibiotics may produce a hypoprothrombinemia that responds readily to small doses of vitamin K. In premature infants and in infants with hemorrhagic disease of the newborn the use of vitamin K may be indicated. However, the main indication for the use of vitamin K is to antagonize the anticoagulant activity of coumarins. Oral absorption of phytonadione and the menaquinones is by the lymph while menadione and its water-soluble derivatives are absorbed directly. The absorption of phytonadione is energy-dependent and saturable. Intravenous administration of phytonadione has produced flushing, dyspnea, chest pains, and cardiovascular collapse. 

Folic acid deficiency, unlike vitamin B12 deficiency, is often caused by inadequate dietary intake of folates. Patients with alcohol dependence and patients with liver disease can develop folic acid deficiency because of poor diet and diminished hepatic storage of folates. Pregnant women and patients with hemolytic anemia have increased folate requirements and may become folic acid-deficient, especially if their diets are marginal. Evidence implicates maternal folic acid deficiency in the occurrence of fetal neural tube defects, eg, spina bifida. (See Folic Acid Supplementation A Public Health Dilemma.) Patients with malabsorption syndromes also frequently develop folic acid deficiency. Patients who require renal dialysis develop folic acid deficiency because folates are removed from the plasma during the dialysis procedure. 

Type IE vitamin D-dependent rickets is caused by a target tissue defect in response to l,25(OH)2D. Studies have shown a number of point mutations in the gene for the l,25(OH)2D receptor, which disrupt the functions of this receptor and lead to this syndrome. The serum levels of l,25(OH)2D are very high in type II but not in type I. Treatment with large doses of calcitriol has been claimed to be effective in restoring normocalcemia. Such patients are totally refractory to vitamin D. One recent report indicates a reversal of resistance to calcitriol when 24,25(OH)2D was given. These diseases are rare. 

There are some well-described deficiency syndromes, the well-established therapeutic use of vitamin K antagonists as oral anticoagulants and the well-known positive effects of pantothenic acid on skin hydration/moisturization and wound healing, which apparently lacks scientific solid base. Apart from that there are not many studies available on the treatment of dermatological disorders with these vitamins, either systemically or topically. Even less is known about transdermal penetration, stability, and formulation dependencies of possible topical applications. 

The fetal warfarin syndrome involves neurological as well as bone abnormalities. Vitamin K-dependent carboxylase is expressed in different brain regions at different times during embryological development. 

I.6. Various Diseases. Abbassy et al. (Al) observed in 12 cases of malnutrition (including kwashiorkor), toxic dyspepsia, 8 cases of acute nephritis, 8 cases of infective hepatitis, and muscular dystrophy an increased spontaneous excretion of xanthurenic acid, the amount of which was found to depend on the severity of the case. In all these cases, with the exception of acute nephritis and hepatitis, the amount of xanthurenic acid was restored to normal levels after vitamin Be therapy. In 8 children with mental retardation, cerebral palsy, recurrent convulsions, 5 with nephrotic syndrome, and 5 with pellagra the amount of xanthurenic acid spontaneously excreted was found to be within the normal range, indicating that pyridoxine is probably not concerned in these cases. 

Vitamin B12 deficiency most frequently is seen in people over 60 years of age (11). Deficiency of vitamin B12 in younger adults is rare, but can occur as a result of reduced absorption of vitamin B12, for example in pernicious anemia, atrophic gastritis type B, long-term use of blockers of acid secretion, or short bowel syndrome after resection of the terminal ileum (18,19). Vitamin B12 deficiency in children usually depends on inborn defects of vitamin Bi2 metabolism or on insufficient support during pregnancy and breastfeeding. 

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