Genes are segments of DNA that hold the instructions for building proteins, which are complex molecules essential for the body’s structure, function, and regulation. One such gene is DDC, whose role and the consequences of its alteration are explored here.
The DDC Gene and Its Enzymatic Product
The Dopa Decarboxylase (DDC) gene, located on chromosome 7, provides the blueprint for an enzyme named Aromatic L-amino acid decarboxylase (AADC). Enzymes are proteins that act as biological catalysts, accelerating chemical reactions within cells.
The AADC enzyme is important for various metabolic pathways. It functions as a homodimer, meaning two identical protein subunits must join to form the active unit. This structure allows it to perform its catalytic role throughout the body, particularly within the nervous system.
Function of the AADC Enzyme in Neurotransmitter Synthesis
The AADC enzyme is involved in producing chemical messengers known as neurotransmitters. It catalyzes the final stage of synthesis for both dopamine and serotonin through a reaction called decarboxylation. This process involves removing a carboxyl group from a precursor molecule, converting L-3,4-dihydroxyphenylalanine (L-DOPA) into dopamine and L-5-hydroxytryptophan (5-HTP) into serotonin.
Dopamine and serotonin are important for communication between nerve cells and regulate numerous bodily functions. Dopamine plays a part in controlling movement, the brain’s reward and pleasure centers, and emotional responses. Serotonin is associated with regulating mood, sleep cycles, appetite, and body temperature.
Impact of DDC Gene Mutations
A mutation in the DDC gene is a change in its DNA sequence that alters the instructions for building the AADC enzyme. These changes can lead to a flawed enzyme structure or reduce the amount produced. When the AADC enzyme is absent or not working correctly, the synthesis of dopamine and serotonin is disrupted.
This malfunction causes a rare genetic disorder known as Aromatic L-amino acid decarboxylase (AADC) deficiency. AADC deficiency is an autosomal recessive condition, meaning an individual must inherit two mutated copies of the DDC gene—one from each parent—to develop it. Individuals who inherit only one mutated copy are carriers but do not show symptoms. More than 50 different mutations in the DDC gene have been identified as causes of this deficiency.
Recognizing AADC Deficiency Symptoms and Diagnosis
The clinical signs of AADC deficiency emerge within the first few months of life and progress over time. Initial symptoms include developmental delays, hypotonia (weak muscle tone), and feeding difficulties. Later symptoms include:
- Movement disorders like dystonia (involuntary muscle contractions)
- Oculogyric crises, which are prolonged, involuntary upward movements of the eyes
- Autonomic nervous system dysfunction, causing issues with temperature and blood pressure regulation
- Excessive sweating and nasal congestion
Diagnosing AADC deficiency involves several methods. A biochemical analysis of cerebrospinal fluid (CSF) will reveal low levels of dopamine and serotonin byproducts, alongside elevated levels of their precursors, L-DOPA and 5-HTP. A definitive diagnosis is achieved through genetic testing, which identifies mutations in both copies of the DDC gene. Enzyme assays can also directly measure AADC enzyme activity to confirm a deficiency.
Therapeutic Strategies for AADC Deficiency
Managing AADC deficiency involves symptomatic treatments and supportive care. Medications can alleviate specific symptoms, such as dopamine agonists to increase dopamine-related activity and MAO inhibitors to slow the breakdown of existing dopamine. Other drugs may manage movement disorders and sleep disturbances. Supportive care includes physical, occupational, and speech therapy, along with nutritional support to help with muscle function and feeding.
Gene therapy is a newer treatment for AADC deficiency. One specific therapy, eladocagene exuparvovec, delivers a functional copy of the DDC gene directly to brain cells using a modified virus as a transport vehicle. This process allows the targeted neurons to produce their own functional AADC enzyme, restoring the dopamine and serotonin synthesis pathways. Research continues to refine this and other therapeutic approaches for the condition.