Vitamin-responsive inherited metabolic

These disorders can be thought of as relative vitamin deficiency states. Not all patients will respond to vitamins owing to the existence of pheno-copies. Data from L. E. Rosenberg Vitamin-responsive inherited metabolic disorders. In Advances in Human Genetics, Vol. 6, H. Harris and K. Hirschhom, Eds. (Plenum Press, 1976) and S. H. Mudd Vitamin-responsive genetic abnormalities. In Advances in Nutritional Research, Vol. 4 (Plenum Press, 1982). 

A practical outcome of these discoveries concerns the treatment of patients suffering from vitamin D-resistant rickets, who respond only to huge doses of the vitamin. This condition can result from chronic renal failure or from an inherited metabolic defect affecting the enzyme responsible for hydroxylating 25-HCC at the 1-position. Consequently the kidney cells are... 

The homocystinurias are a group of disorders involving defects in the metabolism of homocysteine. The diseases are inherited as autosomal recessive illnesses, characterized by high plasma and urinary levels of homocysteine and methionine and low levels of cysteine. The most common cause of homocystinuria is a defect in the enzyme cystathionine /3-synthase, which converts homocysteine to cystathionine (Figure 20.21). Individuals who are homozygous for cystathionine [3-synthase deficiency exhibit ectopia lentis (displace ment of the lens of the eye), skeletal abnormalities, premature arte rial disease, osteoporosis, and mental retardation. Patients can be responsive or non-responsive to oral administration of pyridoxine (vitamin B6)—a cofactor of cystathionine [3-synthase. Bg-responsive patients usually have a milder and later onset of clinical symptoms compared with B6-non-responsive patients. Treatment includes restriction of methionine intake and supplementation with vitamins Bg, B, and folate. 

About two dozen inherited diseases respond to pharmacological doses of a vitamin (Table 38-1). Many have been mentioned elsewhere in this book in conjunction with the affected metabolic pathways. Although most are very rare, their study has contributed much to acknowledge of metabolism in the human body. Some are heterogeneous in symptoms and in responsiveness to therapy, suggesting genetic heterogeneity, as discussed above. 

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