Dopamine transporter deficiency syndrome (DTDS), also known as infantile parkinsonism-dystonia, is a rare movement disorder that causes progressively worsening dystonia and parkinsonism. It is the first known inherited dopamine transportophathy. DTDS is an extremely rare disease; only about 20 affected individuals have been described in the medical literature. Researchers believe this condition is likely underdiagnosed because its signs and symptoms overlap with other movement disorders, including cerebral palsy.The onset of DTDS is a continuum that ranges from early-onset DTDS (in the first 6 months) to atypical later-onset DTDS (in childhood, adolescence, or adulthood). Signs and symptoms
The main symptom of DTDS, presenting in 80-99% of DTDS patients, is Parkinsonism. This is a neurological anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, and is characterized by shaking and tremors, rigidity, slowness of movement, and difficulty with walking and gait.Various other symptoms present less commonly (30-79%), including bradykinesia (slowness of movement), acid reflux, muscular hypertonia, and chorea. Causes
DTDS is caused by mutations in the SLC6A3 gene, which codes for the dopamine transporter protein DAT. In contrast to various mutations that up-regulate DAT activity, which is implicated in clinical depression, this mutation results in DAT down-regulation and, consequently, DTDS. Known DTDS-related SLC6A3 mutations include:

R85L
A314V
G386R
R445C
Y470SIn vitro replication of SLC6A3 mutations like those present in DTDS demonstrate multifaceted loss of dopamine transporter functions. Dopamine intake is universally impaired.
Agents
Mineralocorticoid receptor antagonists
An antimineralocorticoid is currently recommended for patients with HFpEF who show elevated brain natriuretic peptide levels. Spironolactone is the first member of this medication class and the most frequently employed. Care should be taken to monitor serum potassium levels as well as kidney function, specifically glomerular filtration rate during treatment. Beta blockers
Beta blockers play a rather obscure role in HFpEF treatment though there is suggestion of a beneficial role in patient management. Evidence from a meta-analysis demonstrated significant reductions in all cause mortality with beta-blocker therapy, though overall effects were driven largely by small, older trials of patients post-myocardial infarction. Some evidence suggests that vasodilating beta blockers, such as nebivolol, can provide a benefit for patients with heart failure regardless of ejection fraction. Additionally, because of the chronotropic perturbation and diminished LV filling seen in HFpEF the bradycardic effect of beta blockers may enable improved filling, reduce myocardial oxygen demand, and lower blood pressure. However, this effect also can contribute to diminished response to exercise demands and can result in an excessive reduction in heart rate.Beta-blockers are the first-line therapy: they lower the heart rate and thus give more time for ventricles to fill. They may also improve survival. Angiotensin converting enzyme (ACE) inhibitors
Likewise, treatment with angiotensin converting enzyme inhibitors, such as enalapril, ramipril, and many others, may be of benefit due to their effect on preventing ventricular remodeling but under control to avoid hypotension. ACE inhibitors do not appear to improve morbidity or mortality associated with HFpEF alone.