In contrast to patients suffering from pterin defects, which also cause and are diagnosable by hyperphenylalaninemia, very few patients have been identified suffering from primary enzyme defects of dopamine or serotonine biosynthesis. From 1995 to 1997 we were able to diagnose 2 families with tyrosine hydroxylase deficiency, 4 families with aromatic L-amino acid decarboxylase deficiency, 3 families with a dominant defect of GTP-cyclohydrolase and a girl with a putative defect of dopamine D2 receptors. Despite clinical presentations suggestive of cerebral dopamine deficiency - combinations of hypokinesia, amimia, rigidity, dystonia (with or without diurnal variation), distal chorea, oculogyric crises, pinpoint pupils, ptosis, infantile myoclonic epilepsy, hypersalivation, and progressive disease course, diagnosis was only achieved years after the onset of symptoms and mostly after more than one sibling was affected (up to 6). In 3 patients neurotransmitter metabolites had already been examined and reported normal due to inadequate analysis or interpretation of results. In contrast to inborn errors of catabolic pathways, neurotransmitter defects are reflected by the interplay of biosynthesis, degradation and receptor status. Even borderline abnormalities can be diagnostic, but require a strictly standardized sampling protocol, and adequate age-related reference values. Diagnosis may be aided by elevated levels of prolactin in serum, the release of which is inhibited by dopamine via dopamine D2 receptors, but finally requires optimized analysis of a spectrum of neurotransmitter metabolites in CSF.