Given MANEA's role in carbohydrate metabolism and its relatively minor expression in brain, initially it would not appear to be a good biological candidate to modulate susceptibility to CD or its associated psychotic complications. However, insight into the relationship between MANEA, paranoia, and CD can be gleaned from studies of mannosidase and other glycoproteins. α-Mannosidosis in humans is a rare autosomal recessive lysosomal storage disorder associated with decreased activity of mannosidase. Recently, α-mannosidosis was identified as the underlying cause of recurrent paranoid hallucinatory episodes in a 27-year-old woman.38 α-Endomannosidase is 1 of several glycosidic enzymes that remove oligosaccharide chains of dopamine β-hydroxylase,39 the enzyme that converts dopamine to norepinephrine. Low levels of β-hydroxylase in plasma or cerebrospinal fluid and polymorphisms in β-hydroxylase have been associated with greater vulnerability to psychotic symptoms in several psychiatric disorders including CD,23,40 schizophrenia,41 and major depression.42 α-Endomannosidase may also influence susceptibility to CD by modifying the function of liver carboxylesterase, a glycoprotein of the high mannose type,43 2 forms of which hydrolyze cocaine and other drugs.44,45
