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Disease Profile

Dopamine transporter deficiency syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

-

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Parkinsonism-dystonia infantile; Infantile Parkinsonism-dystonia; DTDS;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Dopamine transporter deficiency syndrome (DTDS) is a rare movement disorder that causes progressive (worsening) dystonia and parkinsonism. It usually begins in infancy ('classic DTDS') and for this reason, it is also known as 'infantile parkinsonism dystonia.' However, some people with DTDS may not develop symptoms until childhood or later (which is known as 'atypical DTDS').[1][2][3]

The dystonia in DTDS is characterized by uncontrollable (involuntary), long-lasting muscle contractions and cramps that involve many different muscles. Dystonia causes difficulty with daily activities and impairs the ability to talk, eat, drink, pick up objects, and walk. Parkinsonism develops as the disorder progresses and is characterized by tremor (shaking), slowed movements (bradykinesia), rigidity (stiffness), and impaired balance and coordination. Additional symptoms that may be present include abnormal eye movements, reduced facial expressions, irritability, sleeping problems, digestive problems (such as reflux or constipation), and recurrent pneumonia which can be life-threatening.[2][3] Classic DTDS is associated with a poor outlook (prognosis), and death may occur in the teenage years due to unexplained sudden causes or respiratory complications.[1][2][3][4] Those with atypical DTDS may have milder symptoms and a longer lifespan, but the long-term outlook for this form is not well-known.[1][2]

DTDS is caused by mutations in the SLC6A3 gene and inheritance is autosomal recessive.[2][3][4] There is no cure for DTDS; treatment aims to relieve symptoms and increase quality of life. Treatment may include medicines to control involuntary movements (such as tetrabenazine and benzodiazepines), medicines to control dystonia (such as pramipexole and ropinirole), and physical therapy to reduce the risk of contractures from muscle rigidity.[3]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Parkinsonism
0001300
30%-79% of people have these symptoms
Abnormal circulating carboxylic acid concentration
0004354
Abnormal pyramidal sign
0007256
Absent speech
Absent speech development
Lack of language development
Lack of speech
No speech development
No speech or language development
Nonverbal

[ more ]

0001344
Bradykinesia
Slow movements
Slowness of movements

[ more ]

0002067
Cerebral palsy
0100021
Chorea
0002072
Constipation
0002019
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

0002020
Global developmental delay
0001263
Hypokinesia
Decreased muscle movement
Decreased spontaneous movement
Decreased spontaneous movements

[ more ]

0002375
Hypomimic face
Dull facial expression
0000338
Irritability
Irritable
0000737
Limb hypertonia
Increased muscle tone of arm or leg
0002509
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Oculogyric crisis
0010553
Orofacial dyskinesia
0002310
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Delayed gross motor development
Delayed motor skills
0002194
Dyskinesia
Disorder of involuntary muscle movements
0100660
Hyperkinetic movements
Muscle spasms
0002487
Hypertonia
0001276
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Limb dystonia
0002451
Morphological abnormality of the pyramidal tract
0002062
Ocular flutter
0031931
Progressive
Worsens with time
0003676
Rigidity
Muscle rigidity
0002063
Tremor
0001337

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Dopamine transporter deficiency syndrome. This website is maintained by the National Library of Medicine.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Dopamine transporter deficiency syndrome. Click on the link to view a sample search on this topic.

          References

          1. Ng J, Zhen J, Meyer E, et al. Dopamine transporter deficiency syndrome: phenotypic spectrum from infancy to adulthood. Brain. April, 2014; 137(Pt 4):1107-1119. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959557/.
          2. Dopamine transporter deficiency syndrome. Genetics Home Reference (GHR). October, 2015; https://ghr.nlm.nih.gov/condition/dopamine-transporter-deficiency-syndrome.
          3. Kurian MA. SLC6A3-Related Dopamine Transporter Deficiency Syndrome. GeneReviews. July 27, 2017; https://www.ncbi.nlm.nih.gov/books/NBK442323/.
          4. Cassandra L. Kniffin. PARKINSONISM-DYSTONIA, INFANTILE, 1; PKDYS1. Online Mendelian Inheritance in Man (OMIM). January 29, 2014; https://www.omim.org/entry/613135.