Pediatric Neurotransmitter Deficiency Disorders
What are Pediatric Neurotransmitter Deficiency Disorders (PNDs)?
The term “neurotransmitter disorders” constitutes a broad and increasingly complex spectrum of neurologic conditions associated with defects in the production, transport, release and reuptake of a variety of chemical compounds involved in the ability of nerve cells in the brain and spinal cord to communicate with each other (see figure 1). The purpose of this section is to provide an overview of such disorders, with an emphasis on disorders associated with a dopamine or serotonin deficiency state.
Screening for this group of disorders occurs mostly by recognition of key neurologic symptoms (reviewed under symptoms), at the discretion of the examining neurologist, rather than a standardized diagnostic evaluation. Symptoms such as a dystonic gait disorder, childhood-onset parkinsonism, or involuntary eye movements have a much higher likelihood of an associated dopamine deficiency state, and patients with classic symptoms therefore have a greater likelihood of receiving accurate diagnosis and treatment.
However, the wide spectrum of symptoms associated with dopamine deficiency states and overlap with other disorders with shared features can make accurate diagnosis of these disorders challenging. The routine availability of more sophisticated diagnostic tools including cerebrospinal fluid (CSF) neurotransmitter metabolite studies, CSF and urine biopterin studies, neuroimaging studies (MRI or more specific scans, such as PET), phenylalanine loading studies, enzyme assays in blood cells or skin fibroblasts, and molecular studies have greatly increased our ability to accurately diagnose and treat patients in a timely fashion.
For ease of classification, these disorders can be divided into four groups:
- neurotransmitter deficiency states with hyperphenylalaninemia
- neurotransmitter deficiency states without hyperphenylalaninemia
- secondary neurotransmitter deficiency states
- disorders of neurotransmitter metabolism
