Inherited disorders of amine biosynthesis

Abstract

Amine biosynthetic defects that result in dopamine deficiency encompass an increasingly broad spectrum of neurological phenotypes. This review highlights observations from the literature in addition to the author’s personal perspectives from ongoing studies of individuals and families with a select subset of these disorders: aromatic L-amino acid decarboxylase deficiency and dopa-responsive dystonia due to guanine triphosphate cyclohydrolase 1 and tyrosine hydroxylase deficiencies. These disorders, while demonstrating a shared dopamine deficiency state, highlight the complexities of the dopaminergic pathways in relation to variables including gender, circadian variation in neurotransmitter levels, receptor expression and neurological development. An improved understanding of the mechanisms involved in phenotypic expression and responses to treatment in inborn errors of amine biosynthesis will undoubtedly lead to advances in our understanding and treatment of more complex and common neurological disorders, such as Parkinson’s disease.