In humans characterization

Thiuram, the ethyl analog of thiram, was reported to cause peripheral neuropathy in humans (characterized by pain, numbness, and weakness in the extremities). Occupational exposure to maneb-containing fungicides caused extrapyramidal symptoms in two agricultural workers. In addition to the previously mentioned symptoms, mental confusion, drowsiness, lethargy, and flaccid paralysis were reported to occur with thiram poisoning. 

GPI-deficient mammalian cells are viable in tissue culture and many GPI-deficient mutant cell lines have been established. However, GPI deficiency has major consequences at the level of tissues and the whole body. This was revealed in transgenic mouse models in which the PIG-A gene (required for the first step of GPI biosynthesis) was knocked out in specific tissues or in the whole animal. For example, keratinocyte-specific disruption of PIG-A caused abnormal development of skin leading to death of the mutant mice a few days after birth (M. Tarutani, 1997), and disruption of PIG-A in the whole animal resulted in embryos that did not develop beyond day 9 of gestation (M. Nozaki, 1999). A somatic mutation of PIG-A in multipotent hematopoietic human stem cells causes paroxysmal nocturnal hemoglobinuria, an acquired hemolytic disease in humans characterized by abnormal activation of complement on erythrocytes due to a deficiency of GPI-anchored complement regulatory proteins such as decay accelerating factor (N. Inoue, 2003). This disease is characterized by intravascular hemolysis and anemia. 

XDH deficiency is also observed in xanthinuria, a genetic disease in humans characterized by low urinary output of uric acid and high levels of xanthine and hypoxan-thine in the blood and urine. Clinical manifestations develop only after the formation of renal calculi or deposition of xanthine and hypoxanthine in muscles has resulted in a mild myopathy. To date, some 50 cases of this disease have been reported. 

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