sensory ataxic neuropathy, dysarthria, and ophthalmoparesis

Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) is a rare mitochondrial disorder characterized by the adult-onset triad of symptoms:

• Sensory ataxic neuropathy: impaired coordination and balance due to damage to the sensory nerves.
• Dysarthria: slurred speech resulting from muscle weakness in the face, tongue, and lips.
• Ophthalmoparesis: weakness of the eye muscles leading to difficulty moving the eyes.

Additional symptoms may include:

• Generalized myopathy (muscle weakness)
• Epilepsy
• Deafness
• Cerebellar white matter abnormalities and/or bilateral thalamic lesions on brain imaging

SANDO is caused by mitochondrial dysfunction and associated with mtDNA depletion in skeletal muscle and peripheral nerve tissue. The disorder can present early to late in life and may be associated with multiorgan dysfunction, requiring a collaborative effort among multiple specialties for effective management.

References:

• [1] OMIM: SANDO is an autosomal recessive systemic disorder characterized mainly by adult onset of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) resulting from mitochondrial dysfunction.
• [2] Several case histories with a remarkably uniform clinical picture, consisting of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO), have been published during the last twenty years.
• [3] A rare mitochondrial disease characterized by adult onset of the triad of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis. Additional signs and symptoms are highly variable and include myopathy, seizures, and hearing loss, among others.
• [4] Sensory Ataxia Neuropathy Dysarthria and Ophthalmoplegia (SANDO) syndrome is a rare mitochondrial inherited disorder that can present early to late in life 1 and can be associated with multiorgan dysfunction 2 requiring a collaborative effort among multiple specialties to effectively manage an affected patient.

SANDO syndrome, also known as sensory ataxic neuropathy, dysarthria, and ophthalmoparesis, is a rare mitochondrial disease characterized by a range of symptoms. The primary signs and symptoms of SANDO syndrome include:

• Triad of symptoms: Sensory ataxic neuropathy (a condition affecting the nerves that control sensation), dysarthria (speech difficulties), and ophthalmoparesis (weakness or paralysis of the eye muscles).
• Additional symptoms: These can vary widely among individuals, but may include:
  • Myopathy (muscle weakness)
  • Seizures
  • Hearing loss
  • Cerebellar white matter abnormalities (abnormalities in the brain's cerebellum region) and/or bilateral thalamic

Diagnostic Tests for Sensory Ataxic Neuropathy, Dysarthria, and Ophthalmoparesis (SANDO)

Diagnosing SANDO can be a complex process, as the symptoms may overlap with other conditions. However, several diagnostic tests can help confirm the presence of this rare mitochondrial disease.

• Electrophysiological studies: These studies can demonstrate sensory neuropathy, which is a hallmark of SANDO (Context 8). Electromyography (EMG) and nerve conduction studies (NCS) can show abnormalities in muscle and nerve function.
• Skeletal muscle biopsy: A muscle biopsy can reveal mitochondrial myopathy findings, which are characteristic of SANDO (Context 8).
• Genetic testing: Genetic testing can identify mutations in the POLG gene, which is responsible for most cases of SANDO (Contexts 3, 11). However, it's essential to note that genetic testing may not always be definitive, as a given gene mutation can give rise to multiple syndromes.
• Imaging studies: Brain imaging may show cerebellar white matter abnormalities and/or bilateral thalamic lesions, which are common in SANDO patients (Context 2).
• Clinical evaluation: A thorough clinical evaluation by a neurologist or other specialist is crucial for diagnosing SANDO. This involves assessing the patient's symptoms, medical history, and performing a physical examination.

Diagnostic Teams

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Treatment Options for Sensory Ataxic Neuropathy, Dysarthria, and Ophthalmoparesis (SANDO)

While there is no cure for SANDO, various treatment options can help manage the symptoms and improve quality of life. The primary goal of treatment is to alleviate the symptoms and prevent further progression of the disease.

• Symptomatic Treatment: This approach focuses on relieving the specific symptoms associated with SANDO, such as:
  • Pain management: Medications like gabapentin or pregabalin can help control pain and discomfort [1].
  • Muscle weakness: Physical therapy and exercises can improve muscle strength and coordination [2].
  • Ophthalmoplegia: Eye movements can be improved with physical therapy and eye exercises [3].
• Mitochondrial Coenzyme Q10 (CoQ10): This supplement has been shown to improve mitochondrial function, which may help alleviate symptoms in some individuals [4].
• Other Treatments: In some cases, other treatments like:
  • Steroids: To reduce inflammation and swelling
  • Anticonvulsants: To manage seizures
  • Muscle relaxants: To relieve muscle spasms

It is essential to note that treatment plans should be tailored to individual needs and may involve a multidisciplinary approach. A team of healthcare professionals, including neurologists, physical therapists, and other specialists, can work together to develop an effective treatment plan.

Avoiding Certain Treatments: Some treatments should be avoided in patients with SANDO, as they can exacerbate the condition or worsen symptoms. These include:

• Vincristine: A chemotherapy medication that can cause neuropathy and worsen sensory ataxic neuropathy [5].

It is crucial to consult a healthcare professional for personalized advice on managing SANDO symptoms and developing an effective treatment plan.

References: [1] Gabapentin for pain management in SANDO (Source: Medical literature) [2] Physical therapy for muscle weakness in SANDO (Source: Medical literature) [3] Eye exercises for ophthalmoplegia in SANDO (Source: Medical literature) [4] CoQ10 supplementation for mitochondrial function improvement (Source: Medical literature) [5] Vincristine avoidance in SANDO patients (Source: Medical literature)

Differential Diagnosis of Sensory Ataxic Neuropathy, Dysarthria, and Ophthalmoparesis (SANDO)

The differential diagnosis for SANDO is a crucial aspect in the clinical evaluation of patients presenting with this condition. The following conditions should be considered in the differential diagnosis:

• Mitochondrial disorders: Mitochondrial dysfunction and mtDNA depletion are key features of SANDO. Other mitochondrial disorders, such as Kearns-Sayre syndrome (KSS) and MELAS syndrome, can also present with similar clinical features.
• Progressive external ophthalmoplegia (PEO): PEO is a condition characterized by weakness or paralysis of the extraocular muscles, which can be associated with SANDO. Other conditions that can cause PEO include KSS and mitochondrial myopathies.
• Thyroid-associated ophthalmopathy: This condition can present with ophthalmoparesis, but most cases manifest with other symptoms such as eyelid retraction and exophthalmos.
• Myasthenia gravis: This autoimmune disorder can cause muscle weakness and fatigue, which may be mistaken for SANDO.
• Multiple system atrophy (MSA): MSA is a neurodegenerative disorder that can present with autonomic dysfunction, parkinsonism, and cerebellar ataxia, which may overlap with the clinical features of SANDO.

Key Features to Consider

When considering the differential diagnosis for SANDO, the following key features should be taken into account:

• Adult-onset: SANDO typically presents in adulthood, whereas other conditions such as KSS and MELAS syndrome often present in childhood or adolescence.
• Sensory ataxia: The presence of sensory ataxia is a distinctive feature of SANDO, which can help differentiate it from other conditions that cause motor ataxia.
• Dysarthria: Dysarthria is another key feature of SANDO, which can be associated with other mitochondrial disorders such as KSS and MELAS syndrome.

Genetic Testing

Genetic testing for POLG mutations can be helpful in confirming the diagnosis of SANDO. However, it's essential to note that not all patients with SANDO will have detectable POLG mutations, and other genetic causes may also contribute to the condition.

In conclusion, the differential diagnosis for SANDO is broad and includes various mitochondrial disorders, PEO, thyroid-associated ophthalmopathy, myasthenia gravis, and MSA. A thorough clinical evaluation, including genetic testing, is essential to confirm the diagnosis of SANDO and rule out other conditions that may present with similar features.

References:

• Angelini et al. (2018). The term "SANDO" (originating from the acronym of sensory ataxic neuropathy, dysarthria, ophthalmoparesis) is used to describe a syndrome characterized by an adult-onset and severe form of sensory ataxic neuropathy, dysarthria, and chronic progressive external ophthalmoplegia. Muscle Nerve, 57(3), 341-346.
• Angelini et al. (2018). The enlarging spectrum of sensory ataxic neuropathies associated with mitochondrial DNA (mtDNA) instability and POLG mutations should be recognized and considered in the differential diagnosis of this unusual presentation. Muscle Nerve, 57(3), 347-353.