Abstract
Neurotransmitter deficiencies are rare neurological disorders with clinical onset
during childhood. The disorders are caused by genetic defects in the enzymes involved
in synthesis, degradation, or transport of neurotransmitters or by defects in the
cofactor biosynthesis such as tetrahydrobiopterin (BH4). With the newly described DNAJC12 deficiency, a chaperon-associated neurotransmitter
disorder, the pathophysiological spectrum has been broadened. All deficiencies result
in a lack of monoamine neurotransmitters, especially dopamine and its products, with
a subset leading to decreased levels of serotonin. Symptoms can occur already in the
neonatal period. Classical signs are hypotonia, movement disorders, autonomous dysregulations,
and impaired development. Diagnosis depends on quantitative detection of neurotransmitters
in cerebrospinal fluid, since peripheral markers in blood or urine are less reliable.
Treatment is based on supplementation of the missing neurotransmitter precursors or
restoring deficient cofactors for endogenous enzymatic synthesis. In recent years,
knowledge about this orphan group of diseases increased substantially among clinicians.
However, the difficult task of integrating clinical symptoms and laboratory values
still leads to a critical delay in diagnosis and therapy for patients. This review
aims at enhancing the understanding of neurotransmitter disorders and should help
practicing clinicians to choose useful diagnostic steps on the way to a valid diagnosis.
Keywords
inherited monoamine neurotransmitter deficiency - pterin synthesis defect - pediatric
movement disorders - parkinsonism - dystonia - L-dopa
