Diagnóstico - ataxia.info

Diagnosis

Information for those recently diagnosed with ataxia or seeking confirmation of diagnosis through genetic testing.

Looking for a diagnosis?

If you or someone you know suspects ataxia and is looking to confirm this diagnosis, here is some information that may help.

BE PATIENT.

Diagnosing rare diseases in Brazil can be difficult and time-consuming. However, it's important to attempt a definitive diagnosis of ataxia to confirm (when possible) the patient's type of ataxia.
In the case of hereditary ataxias (genetic basis), confirmation is made by molecular genetic testing (DNA testing).
There are different types of genetic tests for diagnosing ataxias (see the videos below for more information).
Some types of ataxias are not detected by conventional diagnostic techniques such as standard PCR and may require sophisticated testing. For example, the diagnosis of SCA27B ataxia requires Long Read Sequencing (Oxford Nanopore, PacBio). This technique is expensive and difficult to access outside of specialized centers.
On your journey to a diagnosis, follow the guidance of a neurologist or geneticist.

Diagnosis of ataxias through the Brazilian Public Health System (SUS)

The SUS (Brazilian Health System) has several specialized centers that provide free genetic diagnosis of rare diseases, including some types of ataxias. This service is generally available at university hospitals (Unicamp, USP, UFMG, UFRGS) and at some specialized units, such as the SARAH Network (which has several units in different Brazilian states) and the Casa dos Raros (House of the Rare) in Porto Alegre, Rio Grande do Sul.

Genetic tests for diagnosing ataxias

DNA tests for diagnosing ataxias (genetic testing)

Diagnosing a genetically based ataxia can be a difficult, expensive, and time-consuming process in Brazil.

In the SARAH network , it is possible to obtain a diagnosis through the SUS (Brazilian Unified Health System), as well as at some university hospitals that conduct ataxia research. In the private sector, some health plans cover the DNA test.

Try to find out!

Let's see what the options are.

1. GENE PANEL (PCR + Sanger)
(Targeted Sequencing)

Focus on genes associated with the most prevalent ataxias (e.g., ATXN1, ATXN2, FXN).
Based on PCR amplification and Sanger sequencing, the gold standard method for analyzing specific regions.
Faster.
Relatively low cost and high accuracy for point mutations and small expansions in known genes.

Limitations: Analyzes a few genes at a time. Looks for mutations only in specific regions of selected genes. Does not detect structural variants (e.g., deletions and duplications) or mutations outside the genes included in the panel.

If there is a known family history (e.g., SCA3), the doctor may directly order a specific test to confirm the mutation in a single gene (e.g., "CAG expansion in the ATXN3 gene" to confirm suspected SCA3 ataxia).

Note! There is also a more sophisticated panel, the Multigene Panel by NGS (Next Generation Sequencing) , which offers greater genetic coverage (compared to Sanger sequencing).

"Panel": set of predefined genes to be analyzed (e.g., genes associated with ataxias).
"Multigenic": involves multiple genes related to a specific clinical phenotype .
"NGS": technology that allows the simultaneous reading of several regions of DNA, with high sensitivity that allows the identification of rare or unexpected variants in related genes.

These panels analyze only specific, pre-selected genes and are useful when there is a well-defined clinical suspicion, as in the case of hereditary ataxias, genetic epilepsies, or neuromuscular diseases.

2. EXOME (WES)
Whole Exome Sequencing (WES)

Analyzes all coding regions (exons) of ~20,000 genes.
Covers about 90%-95% of the exome.
Allows detection of mutations in rare or new genes.
Intermediate cost between panels and the Whole Genome (WGS).

Limitation: It does not detect deep intron mutations. For example, the Exome is not capable of diagnosing SCA27B ataxia (caused by intronic GAA expansion in the FGF14 gene).

3. GENOME (WGS)
Whole Genome Sequencing (WGS)

Analyzes all DNA: exons, introns and intergenic regions.
Detects mutations that Exome (WES) or panels cannot detect, such as deep intron mutations, complex structural variants, and variations in regulatory regions.

Disadvantage: Very high cost. Significantly more expensive than WES and panels. Generates a lot of information , much of it without known clinical relevance, requiring careful filtering (by bioinformatics).

Quick Summary

Traditional Gene Panel (PCR + Sanger) → Ideal for the most common ataxias. Confirmation of known mutations (e.g., SCA3/CAG repeats).
Panel Multigenic NGS Panel → Broader investigation of genetic causes of some ataxia (where there is suspicion of more than one gene associated with the clinical picture, for example, as it can detect variants in several genes at the same time). It is also important to consider that there are still many types of hereditary ataxias whose associated genes are not yet known , therefore, there are no specific genetic tests for their diagnosis. In these cases, other tests may be able to diagnose "ataxia," but without specifying the exact subtype or clearly understanding which mutation causes the disease. These ataxias are treated as idiopathic, or of "still unknown cause".
Exome (WES) → For atypical cases or when the panel is inconclusive.
Genome (WGS) → For very rare cases or suspected intronic mutations.

Consult a specialized neurologist or geneticist to find out which test is best for you!

Note! The initial identification of the GAA expansion in the FGF14 gene, which causes SCA27B, required the use of long - read sequencing on platforms such as Oxford Nanopore or PacBio SMRT. After molecular characterization of the mutation, the diagnosis of SCA27B can now be performed clinically using the Repeat-Primed PCR method, which specifically confirms the presence of pathogenic GAA expansions. This process exemplifies the complexity of genetic diagnosis in hereditary ataxias, where research technologies (such as long-read sequencing) and clinical methods (such as PCR) work in a complementary manner.

Recent diagnosis

If you have a recent diagnosis of ataxia:

Read the information about the different types of ataxias on the Ataxia Map, or look in the ATAXIA FACT SHEETS menu for the technical sheet corresponding to the type of ataxia you were diagnosed with.
If you live in Brazil, register with ABAHE (Brazilian Association of Hereditary and Acquired Ataxias).
Keep yourself well-informed and take part in support groups that interest you. These groups — made up of people with ataxia, family members, and friends — share experiences of living with the disease and receive some of the latest information about treatments.
Arrange medical follow-up with a neurologist, either through the public health system or privately. Ask your doctor for referrals to neurological physiotherapy and other specialties if needed. See the section Monitor your health later on.

When progressive ataxia is diagnosed for the first time, most patients have never heard of the condition and do not know anyone with it. At this stage, the help provided by patient support organizations can be crucial. The opportunity to meet others in the same situation, receive emotional support and information, and learn how others cope with the symptoms can be of great benefit to people with ataxia..

It is also important to understand that everyone has their own journey in accepting this diagnosis.

Monitor your health

Ataxias are serious conditions, and it is important for patients to have regular medical follow-up with a neurologist. Depending on the symptoms presented and the type of ataxia diagnosed, a multidisciplinary team including ophthalmologists, physical therapists, speech therapists, occupational therapists, psychologists, and other health professionals may be involved in their care.

Patients with Friedreich's ataxia should be monitored by a cardiologist. Cardiac abnormalities are common in Friedreich's ataxia, and referral to a cardiologist is necessary. "Fredericos" often develop scoliosis and may develop "pes cavus," and, depending on the case, referral to an orthopedic surgeon specializing in foot and ankle surgery is recommended.
Many ataxias are associated with ocular symptoms , such as reduced vision, double vision (diplopia) , or oscillopsia (the impression that objects are oscillating) due to nystagmus . Referral to a neuro-ophthalmologist and other specialized services is recommended, as treatment may be available in many cases.
In addition to motor problems, some ataxias can cause affective-cognitive symptoms such as depression, anxiety, irritability, and other mood disorders. Therefore, psychological counseling is recommended, and if necessary, a referral to a psychiatrist is recommended in severe cases of depression, dementia, or psychosis.
Patients with ataxia may experience dysarthria (speech difficulties). Dysarthria becomes more common as the disease progresses. Symptoms of dysphagia (swallowing difficulties) may also appear . In these cases, referral to a speech-language pathologist is important.
For all patients with any type of ataxia, NEUROFUNCTIONAL PHYSIOTHERAPY IS VERY IMPORTANT.

References

Video:

Newly Diagnosed with Ataxia

Author/website:

Language:

Date:

NAF (National Ataxia Foundation) - Dr. Pravin Khemani

English. You can enable subtitles and configure automatic translation of subtitles into Portuguese.

Jun 14, 2021