classic dopamine transporter deficiency syndrome

Classic Dopamine Transporter Deficiency Syndrome (DTDS) Description

Classic DTDS, also known as infantile parkinsonism-dystonia, is a rare movement disorder that affects infants and young children [1]. The condition is characterized by a range of symptoms, including:

• Nonspecific findings: Infants with DTDS may exhibit irritability, feeding difficulties, axial hypotonia (weakness in the muscles of the trunk), and/or delayed motor development [2].
• Dystonia: People with DTDS develop a pattern of involuntary, sustained muscle contractions known as dystonia. This can lead to abnormal postures and movements [5].
• Rigidity and tremors: Individuals with DTDS may experience rigidity (inflexibility) and tremors, which are symptoms commonly associated with Parkinson's disease [6].
• Chorea, ballismus, and orolingual dyskinesia: Some people with DTDS may exhibit chorea (involuntary movements), ballismus (large, sweeping movements of the arms), and orolingual dyskinesia (abnormal movements of the lips and tongue) [8][9].

These symptoms can appear in infancy and progress over time, mimicking cerebral palsy or other neurological disorders [7]. The condition is caused by variants of the SLC6A3 gene encoding the human dopamine transporter (DAT), which plays a crucial role in regulating dopamine levels in the brain [4].

References:

[1] Oct 1, 2015 — Dopamine transporter deficiency syndrome is a rare movement disorder. [2] by RVV Spaull · 2023 · Cited by 1 — Classic early-onset DTDS: Infants typically manifest nonspecific findings (irritability, feeding difficulties, axial hypotonia, and/or delayed ... [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] Oct 1, 2015 — People with dopamine transporter deficiency syndrome develop a pattern of involuntary, sustained muscle contractions known as dystonia. The ... [6] Dopamine transporter deficiency syndrome ; Rigidity, tremors, slowness of movement, Parkinsonism-dystonia. [7] by J Ng · 2014 · Cited by 168 — Dopamine transporter deficiency syndrome is an SLC6A3-related progressive infantile-onset parkinsonism-dystonia that mimics cerebral palsy. [8] Definition: A dopamine transporter deficiency syndrome characterized by infantile onset of chorea, dystonia,

Classic Dopamine Transporter Deficiency Syndrome (DTDS) Signs and Symptoms

Classic DTDS presents with a range of signs and symptoms that can vary in severity and onset. Some common features include:

• Non-specific findings: Infants may exhibit irritability, feeding difficulties, axial hypotonia (muscle weakness), and delayed motor development [5].
• Neonatal distress and irritability: This is often one of the first signs of DTDS, indicating a problem with dopamine regulation in the brain [3].
• Motor developmental delay: Children with DTDS may experience delays in reaching motor milestones, such as sitting, standing, or walking [4].
• Abnormal eye movements: Some individuals with DTDS may exhibit abnormal eye movements, including ocular flutter and saccadic initiation failure [2].

Other possible symptoms

In addition to these primary signs and symptoms, people with classic DTDS may also experience:

• Action tremor
• Aggressive behavior
• Anxiety
• Cerebellar ataxia
• Cerebellar atrophy
• Chorea (involuntary movements)
• Depression
• Developmental regression

Diagnostic Tests for Classic Dopamine Transporter Deficiency Syndrome

Classic dopamine transporter deficiency syndrome (DTDS) is a complex movement disorder that can be challenging to diagnose. However, several diagnostic tests and evaluations can help establish the condition.

• Laboratory tests: These include urine organic acids, nerve conduction studies, and brain magnetic resonance imaging (MRI). According to [6], laboratory tests were unremarkable in reported cases of DTDS.
• Imaging studies: MRI may show abnormalities in the brain, such as changes in the substantia nigra or putamen. However, these findings are not specific to DTDS and can be seen in other conditions as well.
• Cerebrospinal fluid (CSF) analysis: CSF neurotransmitter analysis profile can help identify raised HVA levels, a stable metabolite of dopamine [15].
• Genetic testing: Molecular genetic testing is essential for establishing the diagnosis of DTDS. This involves looking for biallelic mutations in the SLC6A3 gene.

It's worth noting that the diagnosis of DTDS often requires a combination of clinical evaluation, laboratory tests, and imaging studies. A thorough medical history, physical examination, and review of symptoms are crucial in identifying this condition.

References:

[6] Laboratory tests were unremarkable in reported cases of DTDS. [15] CSF neurotransmitter analysis profile can help identify raised HVA levels, a stable metabolite of dopamine.

Treatment Options for Classic Dopamine Transporter Deficiency Syndrome

Classic dopamine transporter deficiency syndrome (DTDS) is a complex movement disorder that requires prompt and effective treatment to manage its symptoms. While there are no specific treatments approved by the FDA for DTDS, various medications have been used to alleviate its symptoms.

• Levodopa: Levodopa may be prescribed for Parkinson’s disease, which shares some similarities with classic early-onset DTDS [2].
• Dopamine agonists: Dopamine agonists such as pramipexole (Mirapex), ropinirole (Requip), or rotigotine (Neupro) may also be used to treat dopamine deficiency in some cases [2].
• Tetrabenazine: Tetrabenazine has been used to control symptoms of chorea and dyskinesia, which are common in DTDS patients [6].
• Trihexyphenidyl: Trihexyphenidyl has also been tried as a treatment option for DTDS, although it may not be effective for all patients [7].

Palliative Treatment

In addition to these medications, palliative treatment aims to control symptoms and improve quality of life. This includes the use of benzodiazepines to treat chorea and dyskinesia [6]. Preliminary experiments have also examined the potential of drugs as pharmacological chaperones of DAT to rescue DTDS mutations [10].

Gene Therapy

Recent advances in gene therapy have focused on targeted delivery of dopaminergic genes for Parkinson's disease and primary neurotransmitter disorders, including dopamine transporter deficiency syndrome (DTDS) [14]. Gene therapies like BGT-DTDS are being investigated as a potentially curative solution for DTDS patients [8].

References:

[2] Treatment of dopamine deficiency depends on the underlying cause. Lifestyle and diet changes. Performing physical activity can help boost dopamine levels in the body. Regular walks, swimming, or ... (Context 4) [6] by J Ng · 2023 · Cited by 12 — Palliative treatment endeavours to control symptoms; this includes the use of tetrabenazine and benzodiazepines to treat chorea and dyskinesia ... (Context 6) [7] by MM Nasehi · 2020 · Cited by 6 — Therapeutic trials with trihexyphenidyl (up to 2 mg 3 times daily), clonazepam (0.35 mg 3 times daily), and baclofen (5 mg 3 times daily) have been tried in some patients [7]. (Context 7) [10] Treatment can be split into three categories: ... Preliminary experiments have examined the potential of drugs to act as pharmacological chaperones of DAT to rescue DTDS mutations. (Context 10) [14] Here, we review recent advances in gene therapy, focused on the targeted delivery of dopaminergic genes for Parkinson's disease and the primary neurotransmitter disorders, AADC deficiency and dopamine transporter deficiency syndrome (DTDS). (Context 14)

Understanding Classic Dopamine Transporter Deficiency Syndrome

Classic dopamine transporter deficiency syndrome (DTDS) is a subset of SLC6A3-related DTDS cases that present in early infancy. This complex movement disorder can be challenging to diagnose, and it's essential to consider differential diagnoses to ensure accurate identification.

Differential Diagnosis Considerations

When diagnosing classic DTDS, the following conditions should be considered as part of the differential diagnosis:

• Cerebral Palsy: A neurological disorder that affects muscle tone, movement, and coordination. Symptoms can include feeding difficulties, irritability, and delayed motor development.
• Juvenile Parkinsonism: A rare condition characterized by tremors, rigidity, and bradykinesia (slow movement) in children and adolescents.
• Mitochondrial Diseases: A group of disorders that affect the mitochondria, the energy-producing structures within cells. Symptoms can include muscle weakness, seizures, and developmental delays.

Key Diagnostic Features

Classic DTDS is typically identified by nonspecific findings, including:

• Irritability
• Feeding difficulties
• Axial hypotonia (weakness in the muscles of the trunk)
• Delayed motor development

These symptoms can be similar to those found in other conditions, making differential diagnosis crucial for accurate identification.

References

• [3] Classic Dopamine Transporter Deficiency Syndrome describes a subset of SLC6A3-related DTDS cases which present in early infancy. This disorder is usually first identified by neonatal distress and irritability, feeding difficulties, and motor developmental delay.
• [4] Dopamine transporter deficiency syndrome remains under-recognized and our data highlights that dopamine transporter deficiency syndrome should be considered as a differential diagnosis for both infantile- and juvenile-onset movement disorders, including cerebral palsy and juvenile parkinsonism.
• [14] SLC6A3-related dopamine transporter deficiency syndrome (DTDS) is a complex movement disorder with a continuum that ranges from classic early-onset DTDS (in the first 6 months) to atypical later-onset DTDS (in childhood, adolescence, or adulthood). Classic DTDS. Infants typically manifest nonspecific findings (irritability, feeding difficulties, axial hypotonia, and/or delayed motor development).