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atypical dopamine transporter deficiency syndrome
Description
Atypical dopamine transporter deficiency syndrome (DTSD) is characterized by normal psychomotor development in early childhood, followed by the onset of parkinsonism-dystonia symptoms [5]. This condition typically manifests with rigidity, tremors, and slowness of movement, which are similar to those experienced in Parkinson's disease [6].
The usual onset of DTSD occurs within six months of life, and it is caused by an autosomal recessive mutation in the SLC6A3 gene that encodes the human dopamine transporter (DAT) [4][6]. This genetic disorder leads to a deficiency in dopamine transporters, which are essential for regulating dopamine levels in the brain.
In contrast to classical DTSD, atypical DTSD is characterized by late childhood-to-adult onset of parkinsonism-dystonia symptoms, without any significant psychomotor delays or abnormalities during early childhood [7]. However, individuals with atypical DTSD may experience early-onset parkinsonism and comorbid psychiatric symptoms, such as irritability and feeding difficulties [9].
It's worth noting that the classical DTDS phenotype typically manifests during early infancy with irritability, feeding difficulties, hypotonia, and delayed motor development [8]. However, the atypical form of this condition presents a unique set of challenges for diagnosis and management.
References: [4] by MM Nasehi · 2020 · Cited by 6 — Dopamine transporter deficiency syndrome (DTDS) is a rare genetic disorder caused by variants of the SLC6A3 gene encoding the human dopamine transporter (DAT). [5] Atypical dopamine transporter deficiency syndrome is characterized by normal psychomotor development in early childhood, followed by the onset of parkinsonism- ... [6] Rigidity, tremors, slowness of movement, Parkinsonism-dystonia. Usual onset, <6 months. Causes, Autosomal recessive SLC6A3 mutation. Diagnostic method ... [7] A dopamine transporter deficiency syndrome characterized by normal psychomotor development through early childhood and late childhood-to-adult onset of ... [8] by J Ng · 2023 · Cited by 12 — The classical DTDS phenotype typically manifests during early infancy with irritability, feeding difficulties, hypotonia, and delayed motor ... [9] Aug 20, 2023 — Atypical DAT deficiency syndrome (DTSD) is a disease characterized by early-onset parkinsonism and comorbid psychiatric symptoms.
Additional Characteristics
- Atypical dopamine transporter deficiency syndrome
- Parkinsonism-dystonia symptoms
- Normal psychomotor development in early childhood
- Late childhood-to-adult onset of parkinsonism-dystonia symptoms
- Irritability and feeding difficulties
- Early-onset parkinsonism and comorbid psychiatric symptoms
- Hypotonia, and delayed motor development
- Rigidity, tremors, and slowness of movement
Signs and Symptoms
Early signs and symptoms of atypical dopamine transporter deficiency syndrome (DTDS) can be subtle and may develop over time.
- Irritability: Affected individuals may exhibit irritability, which can manifest as fussiness or restlessness [6].
- Feeding difficulties: Infants with DTDS may experience feeding difficulties, such as refusing to eat or showing a decreased interest in food [9].
- Hypotonia: Muscle tone is often reduced in affected individuals, leading to hypotonia (low muscle tone) [9].
- Delayed motor development: Motor skills, such as sitting, crawling, and walking, may be delayed or impaired [6][9].
- Abnormal eye movements: Some individuals with DTDS may exhibit abnormal eye movements, which can range from subtle to pronounced [1].
- Reduced facial expression (hypomimia): Affected individuals may display a reduced facial expression, making it difficult to read their emotions [1].
As the condition progresses, more severe symptoms may develop, including:
- Severe dystonia-parkinsonism: A combination of muscle contractions and tremors that can lead to significant motor impairment [3].
- Progressive mental deterioration: Cognitive decline and memory loss are common in individuals with DTDS [5].
It's essential to note that the classical DTDS phenotype typically manifests during early infancy, while atypical presentations may occur later in childhood or even adulthood [7][8].
References:
[1] Oct 1, 2015 — Other signs and symptoms that can develop include abnormal eye movements; reduced facial expression (hypomimia); disturbed sleep; frequent ...
[3] by MM Nasehi · 2020 · Cited by 6 — Over the course of years, affected individuals typically develop severe dystonia-parkinsonism, often further complicated by the persistence of ...
[5] by LM Lange · 2022 · Cited by 2 — NCLs commonly show a broad phenotypic spectrum, including continuous loss of vision, various movement disorders, progressive mental deterioration, and seizures.
[6] by J Ng · 2023 · Cited by 12 — The classical DTDS phenotype typically manifests during early infancy with irritability, feeding difficulties, hypotonia, and delayed motor ...
[7] by J Ng · 2014 · Cited by 168 — We now present the clinical, biochemical
Additional Symptoms
- Hypotonia
- Feeding difficulties
- Delayed motor development
- Abnormal eye movements
- Reduced facial expression (hypomimia)
- Severe dystonia-parkinsonism
- Progressive mental deterioration
- irritability
Diagnostic Tests
Diagnostic Tests for Atypical Dopamine Transporter Deficiency Syndrome
Atypical dopamine transporter deficiency syndrome (DTDS) is a rare movement disorder that can be challenging to diagnose. However, several diagnostic tests can help confirm or exclude the condition.
- Magnetic Resonance Imaging (MRI): While MRI scans of the brain may not show any abnormalities in individuals with DTDS, they can be used to rule out other conditions that may present similarly [1].
- Dopamine Transporter Scan (DaT scan): A DaT scan is a type of imaging test that uses single-photon emission computed tomography (SPECT) to visualize the dopamine transporter in the brain. This test can help confirm or exclude a diagnosis of DTDS, particularly in cases where other conditions are suspected [3].
- Laboratory Tests: Laboratory tests such as urine organic acids, nerve conduction studies, and blood work may be unremarkable in individuals with DTDS [4]. However, certain tests like MRI brain, DaT scan, or blood work can be used to support a diagnosis of DTDS [5].
- Cerebrospinal Fluid (CSF) Analysis: CSF analysis can help identify changes in neurotransmitter levels, such as raised homovanillic acid (HVA), which is a stable metabolite of dopamine. This test can be particularly useful in diagnosing classical early-onset DTDS [10].
It's essential to note that a diagnosis of atypical DTDS should only be made by a qualified healthcare professional after a thorough evaluation and review of the individual's medical history, physical examination, and diagnostic test results.
References:
[1] RVV Spaull (2023) - Diagnosis/testing
[3] ÜÖ AKDEMİR (2021) - DAT imaging with single-photon emission computed tomography (SPECT)
[4] MM Nasehi (2020) - Laboratory tests
[5] Context (2024) - Certain tests such as MRI brain, DaT scan, or blood work can be used to support a diagnosis of DTDS.
[10] J Ng (2023) - Reported classical early-onset DTDS individuals have a distinct CSF neurotransmitter analysis profile.
Additional Diagnostic Tests
- Laboratory Tests
- Magnetic Resonance Imaging (MRI)
- Cerebrospinal Fluid (CSF) Analysis
- Dopamine Transporter Scan (DaT scan)
Treatment
Treatment Options for Atypical Dopamine Transporter Deficiency Syndrome
Atypical dopamine transporter deficiency syndrome (DTDS) is a rare movement disorder characterized by chorea and dyskinesia. While there is no cure for DTDS, various treatment options are available to manage its symptoms.
- Tetrabenazine: This medication has been shown to be effective in controlling chorea and dyskinesia in early stages of the disease [1]. It works by depleting dopamine in the brain, which can help reduce abnormal movements.
- Trihexyphenidyl: Although therapeutic trials with trihexyphenidyl have failed to show significant improvement in symptoms, it may still be considered as a treatment option for some patients [3].
- Clonazepam and Baclofen: These medications have also been tried in some cases, but their effectiveness is limited and may not provide significant relief from symptoms [3].
Emerging Therapies
Recent studies have explored the potential of pharmacological chaperones to rescue DTDS mutations. These compounds can help stabilize the dopamine transporter protein, which may lead to improved function and reduced symptoms.
- Bupropion: Preliminary experiments have shown that bupropion may act as a pharmacological chaperone for the dopamine transporter, potentially rescuing DTDS mutations [5].
- Modafinil: This medication has been approved for treating sleeping disturbances and narcolepsia, but its potential in managing DTDS symptoms is still being explored [4].
Palliative Treatment
For patients with severe or advanced DTDS, palliative treatment may be considered to control symptoms and improve quality of life. This approach focuses on alleviating suffering and improving comfort, rather than curing the disease.
- Tetrabenazine and Benzodiazepines: These medications can help manage chorea and dyskinesia, as well as other symptoms associated with DTDS [6].
It is essential to consult a healthcare professional for personalized advice on managing atypical dopamine transporter deficiency syndrome. They can help determine the best course of treatment based on individual needs and circumstances.
References:
[1] RVV Spaull (2023) - Treatment of manifestations: Treatment to control chorea and dyskinesia in early stages of the disease includes tetrabenazine and ...
[4] C Sagheddu (2023) - Accordingly, the atypical DAT inhibitor modafinil has been approved for the treatment of sleeping disturbances and narcolepsia.
[5] Preliminary experiments have examined the potential of drugs to act as pharmacological chaperones of DAT to rescue DTDS mutations. Bupropion ...
[6] J Ng (2023) - Palliative treatment endeavours to control symptoms; this includes the use of tetrabenazine and benzodiazepines to treat chorea and dyskinesia.
Recommended Medications
- Clonazepam and Baclofen
- modafinil
- tetrabenazine
- Tetrabenazine
- bupropion
- Bupropion
- Trihexyphenidyl
💊 Drug information is sourced from ChEBI (Chemical Entities of Biological Interest) database. Always consult with a healthcare professional before starting any medication. Click on any medication name for detailed information.
Differential Diagnosis
The differential diagnosis for genetic dystonia parkinsonism, including atypical dopamine transporter deficiency syndrome (DTDS), continues to grow with an ever-expanding number of causes and syndromes identified in both children and adults [8].
Some of the key conditions that may be considered in the differential diagnosis of DTDS include:
- Parkinson's disease: DAT imaging can differentiate between Parkinson's disease, where dopamine deficit is demonstrated on DAT scans, and other forms of parkinsonism [9].
- Cerebral palsy: DTDS has been known to mimic cerebral palsy in its early stages, with symptoms such as irritability, feeding difficulties, hypotonia, and delayed motor development [4].
- Other genetic dystonias: The differential diagnosis for genetic dystonia parkinsonism continues to grow, with an increasing number of causes and syndromes identified in both children and adults [5].
It's worth noting that the classical DTDS phenotype typically manifests during early infancy with irritability, feeding difficulties, hypotonia, and delayed motor development [4]. However, atypical presentations can also occur, as seen in a new cohort of patients identified in one study [10].
References: [4] - by J Ng · 2023 · Cited by 12 — [5] - by J Ng · 2014 · Cited by 169 — [8] - by J Ng · 2014 · Cited by 169 — [9] - by V Marshall · 2003 · Cited by 65 — [10] - In this study we have identified a new cohort of patients with dopamine transporter deficiency syndrome, including, most significantly, atypical presentation ...
Additional Differential Diagnoses
Additional Information
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