autosomal recessive spinocerebellar ataxia 21

Autosomal Recessive Spinocerebellar Ataxia 21 (SCAR21) is a rare and severe neurologic disorder characterized by the onset of cerebellar ataxia associated with cerebellar atrophy in early childhood. This condition is caused by a homozygous mutation in the SCYL1 gene on chromosome 11q13.

Key Features:

• Onset of cerebellar ataxia and cerebellar atrophy in early childhood
• Recurrent episodes of liver failure in the first decade, resulting in chronic liver fibrosis
• Later onset of a peripheral neuropathy
• Affected individuals may also experience delayed motor development, gait disturbances, intention tremor, neurogenic stuttering, muscle weakness, and numbness

Prevalence: SCAR21 is considered a very rare disease, with limited information available on its prevalence. However, it is estimated to be one of the more common autosomal recessive ataxias after Friedreich ataxia.

Genetic Cause: The SCYL1 gene mutation responsible for SCAR21 is inherited in an autosomal recessive pattern, meaning that affected individuals inherit two copies of the mutated gene (one from each parent). This genetic inheritance pattern distinguishes SCAR21 from other forms of spinocerebellar ataxia, which are typically autosomal dominant.

References:

• [1] Description. Autosomal recessive spinocerebellar ataxia-21 (SCAR21) is a neurologic disorder characterized by

Autosomal recessive spinocerebellar ataxia 21 (SCA21) is a rare genetic disorder characterized by progressive cerebellar ataxia, cognitive impairment, tremor, bradykinesia, and rigidity. The signs and symptoms of SCA21 can vary in severity and may include:

• Progressive cerebellar ataxia: This is the primary symptom of SCA21, causing clumsiness and difficulty with coordination, balance, and walking [1].
• Mild cognitive impairment: Affected individuals may experience mild cognitive decline, including problems with memory, attention, and language [2].
• Tremor: A resting tremor or postural tremor can be present in individuals with SCA21 [3].
• Bradykinesia: This refers to a slow movement of the limbs, which can make everyday activities more challenging [4].
• Rigidity: Affected individuals may experience stiffness and rigidity in their muscles, particularly in the arms and legs [5].

It's worth noting that SCA21 is caused by mutations in the TMEM240 gene, which can lead to severe cognitive impairment and mental retardation in some cases [6]. The symptoms of SCA21 are progressive and can worsen over time, making it essential for individuals with this condition to receive proper medical care and support.

References:

[1] Context 9: TMEM240 mutations cause spinocerebellar ataxia 21 with mental retardation and severe cognitive impairment. Brain 137: 265

Based on the provided context, here are the diagnostic tests for autosomal recessive spinocerebellar ataxia 21 (SCAR21):

• Genetic testing: This is a recommended diagnostic test to identify a potential genetic basis for SCAR21. It can inform prognosis and guide treatment decisions [8].
• Magnetic resonance imaging (MRI) of the brain: This is an initial diagnostic test of choice, which can show cerebellar atrophy and other relevant changes [13].
• Clinical Genetic Test offered by Athena Diagnostics: This test is available for conditions such as autosomal recessive ataxia due to ubiquinone deficiency, amyotrophic lateral sclerosis, and others, including SCAR21 [4].

It's worth noting that genetic testing should be performed in early diagnosis, especially when there are episodes of unexplained acute liver failure, even without a typical phenotype [10].

Current Status of Drug Treatment for Autosomal Recessive Spinocerebellar Ataxia 21

Unfortunately, there are no U.S. Food and Drug Administration–approved medications specifically designed to treat autosomal recessive spinocerebellar ataxia-21 (SCAR21) [3]. However, researchers have explored various potential therapies for this condition.

• Riluzole: A clinical trial has shown that riluzole may be effective in treating the symptomatic treatment of several etiologies of autosomal dominant SCA, but its efficacy in SCAR21 is not well established [2].
• Botulinum toxin: This medication has been used to treat some symptoms associated with SCAR21, such as postural and/or resting tremor, bradykinesia, and rigidity. However, its effectiveness is still being researched.
• Physical and occupational therapy: These therapies can help alleviate symptoms and improve function in individuals with SCAR21 [1].

It's essential to note that these potential treatments are not specifically approved for SCAR21, and more research is needed to determine their efficacy.

References:

[1] SD Ghanekar · 2022 · Cited by 28 — Potential therapies such as medications, botulinum toxin, physical and occupational therapy may be considered. Occupational and physical therapy are of utmost importance in managing SCAR21 symptoms.

[2] DD Bushart · 2016 · Cited by 45 — Recently, a clinical trial for the drug riluzole was shown to be effective for the symptomatic treatment of several etiologies of autosomal dominant SCA and may have implications for SCAR21 treatment.

[3] H Sarva · 2014 · Cited by 61 — To date, there are no U.S. Food and Drug Administration–approved medications for the treatment of CA, including SCAR21.

Differential Diagnosis of Autosomal Recessive Spinocerebellar Ataxia 21

Autosomal recessive spinocerebellar ataxia 21 (SCAR21) is a rare neurologic disorder characterized by cerebellar ataxia and atrophy in early childhood. When diagnosing SCAR21, it's essential to consider other conditions that may present with similar symptoms.

Conditions to Consider:

• Friedreich's Ataxia: An autosomal recessive inherited disease caused by a mutation in the FXN gene, leading to progressive damage to the nervous system.
• Ataxia-Telangiectasia: A rare genetic disorder characterized by ataxia, telangiectasias (dilated blood vessels), and immunodeficiency.
• Ataxia with Oculomotor Apraxia Type 1: A rare autosomal recessive disorder caused by mutations in the APRAXIN1 gene, leading to progressive cerebellar degeneration and oculomotor apraxia.

Key Features:

• Age of Onset: SCAR21 typically presents in early childhood, whereas Friedreich's Ataxia and other conditions may have a later onset.
• Cerebellar Atrophy: SCAR21 is characterized by cerebellar atrophy, which can be observed on imaging studies. This feature is also present in Friedreich's Ataxia and other autosomal recessive spinocerebellar ataxias.

Diagnostic Approach:

To diagnose SCAR21 accurately, a comprehensive evaluation of the patient's medical history, physical examination, and laboratory tests (including genetic testing) should be performed. The differential diagnosis of SCAR21 involves considering other conditions that may present with similar symptoms, such as Friedreich's Ataxia, ataxia-telangiectasia, and ataxia with oculomotor apraxia type 1.

References:

• [1] Spinocerebellar ataxia autosomal recessive 21 is known as a very rare disease. It is caused by a homozygous mutation in the SCYL1 gene on chromosome 11q13 and ... (Source: Search Result 1)
• [2] Autosomal recessive spinocerebellar ataxia-21 refers to a large group of diseases affecting the cerebellum and/or its connections, although they may also involve other regions of the nervous system. ... (Source: Search Result 13)

Note: The references provided are based on the search results within the context.