Biomarkers for the study of catecholamine and serotonin genetic diseases

In this chapter, current knowledge about biomarkers for the study of genetic diseases leading to monoamine deficiencies (dopamine, adrenaline, noradrenaline, and serotonin) is reviewed. Twelve genetic diseases will be discussed as causes of primary disturbances in monoamine metabolism, including deficiencies in tyrosine hydroxylase, dopamine beta hydroxylase, L-aromatic amino acid decarboxylase, monoamine oxidase A, tetrahydrobiopterin biosynthesis, dopamine transporter 1, and vesicular monoamine transporter type 2. Different biomarkers are available for the diagnosis, treatment, and monitoring of these diseases, which can be divided into peripheral markers (that can be analyzed in blood or urine) and central markers (cerebrospinal fluid analysis is required). Among these biomarkers, biogenic amines (homovanillic and 5-hydroxyindoleacetic acids) are the most informative to confirm the clinical suspicion. Biochemical procedures for the study of these conditions are stated. Genetic analysis is mandatory for the definitive diagnosis of monoamine diseases. Next-generation sequencing techniques are becoming available in clinical ­laboratories, expanding our knowledge in this field.