Dopamine transporter deficiency syndrome ..., (Dopamine transporter deficiency syndrome) - Gen SLC6A3.

Deficiency syndrome dopamine transporter, also known as dystonia parkinsonism-child (IPD) is a rare progressive movement disorder characterized by the development of dystonia , and parkinsonism.

Overall, the disease begins to manifest in childhood through the development of an involuntary movement pattern including sustained muscle contractions (dystonia). Muscle cramps and spasms continuous cause difficulty in performing basic activities such as talking, eating, drinking, picking up objects and walking. As the disease progresses, affected individuals develop parkinsonism features including tremor, bradykinesia, rigidity and postural instability. Other signs and symptoms that may develop include abnormal eye movements, hypomimia, sleep disturbances, frequent episodes of pneumonia and problems with the digestive system, including gastroesophageal reflux and constipation. People with dopamine transporter deficiency syndrome may have a lower life expectancy. Often affected children die of pneumonia and other respiratory problems. When the first signs and symptoms appear later in life, affected individuals can survive to adulthood.

This process is due to mutations in the SLC6A3 gene, located on the short arm of chromosome 5 (5p15.3). This gene encodes a protein called dopamine transporter or DAT. This protein is located in the membrane of certain neurons in the brain, where dopamine transported into the cell. Dopamine is a neurotransmitter that plays important roles in recognition, motivation, behavior and motion control. To transmit signals, dopamine is released in the synaptic junction, where it binds to receptors on the surface of neighboring neurons. Transporter activity determines the amount of dopamine that is present at the synaptic junction and for how long. This activity causes the conveyor act as a primary controller dopamine signaling in the brain.

They have identified at least 25 mutations in the SLC6A3 gene in people with deficiency syndrome dopamine transporter. The mutations described so far have been: missense mutations (12), and -splicing- mutations cutting attachment (1), regulatory mutations (3), small deletions (2), larger deletions (1), and variations of repetition ( 6). Some of the mutations change the amino acids in dopamine transporter protein. Other mutations result encoding an abnormally short or inhibit encoding any functional protein. Mutations in the SLC6A3 gene deteriorate or eliminate the function of the dopamine transporter. A functional transporter deficiency alters dopamine signaling in the brain, because it can not release dopamine in the synaptic junction. As a result, dopamine accumulates in the peripheral areas of neurons. Excess dopamine alters the signaling between neurons and can inhibit pathways that normally trigger the production of more dopamine. Although dopamine plays a fundamental role in the control of movement, it is not clear how an impaired dopamine signaling leads to specific abnormal movements found in people with the syndrome of deficiency of dopamine transporter.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with deficient dopamine transporter syndrome by complete PCR amplification of exons SLC6A3 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).