Diagnosis & Genetic Testing

The first step in diagnosing RTD is a visit with a doctor for a physical exam. The diagnosis of RTD is based on a combination of clinical symptoms, laboratory findings, neuroimaging, neurophysiological testing and molecular genetic testing.  The links below provide information on each of these diagnosis criteria.

1. Clinical signs and symptoms
2. Laboratory findings
3. Neuroimaging (MRI)
4. Neurophysiological testing (EMG, NCS, ABR, VEP)
5. Histopathology (nerve & muscle biopsies)
6. Molecular genetic testing (see below)

The doctor may order multiple tests to determine whether the problems are a result of RTD. Tests may also rule out other problems that could cause some RTD symptoms, such toxic exposure, medications, or other diseases.

The variable presentation of RTD has in the past often caused a significant delay between the onset of symptoms and diagnosis.  Since oral riboflavin supplementation is effective and often lifesaving, it should begin as soon as RTD is suspected by a doctor and continued lifelong unless the diagnosis is excluded by molecular genetic testing.  Please see the Riboflavin Treatment section for more information on treatment.

Molecular genetic testing

Either single-gene testing or multi-gene panel testing approaches can be used for molecular testing.

Singe-gene testing.   Although differences are observed in the phenotype of individuals with RTD Type 2 (SLC52A2 mutations) compared to RTD Type 3 (SLC52A3 mutations) there are enough overlaps in symptoms that if RTD is suspected both the SLC52A2 and SLC52A3 genes should be tested at the same time rather than sequentially. Simultaneous sequence analysis of SLC52A2 and SLC52A3 is performed first.  If only one pathogenic variant is found in either SLC52A2 or SLC52A3, gene-targeted deletion/duplication analysis should be performed.

Multi-gene panel.    There are now many multi-gene panels available that include SLC52A2 and SLC52A3 as well as other genes of interest selected on potentially similar clinical presentations.

In North America there are several laboratories and various gene panels that now test for SLC52A2 and SLC52A3 mutations.   Please visit the NCBI website for a list of all testing sites and how to order.