Sural nerve biopsies on six RTD Type 2 patients with relatively severe presentation were reported by Foley and colleagues (2014). They found a chronic axonal neuropathy with fibrosis and continuous degeneration with no regeneration. Large myelinated fibres were consistently more severely affected. Regeneration was strikingly absent. Unmyelinated fibres were generally better preserved. There were no signs of inflammation, hypomyelination or demyelination seen on the biopsies. The remaining axons were mostly normal or atrophic in a few cases. Biopsies in other RTD Type II patients with milder clinical feature have shown similar features but with some reports of axons with mild demyelination with remyelination. Non-myelinated fibers were found to be well preserved. The absence of regeneration may be more suggestive of a neuronopathy. Preferential involvement of large myelinated fibres may explain the sensory ataxia and areflexia.
A sural nerve biopsy taken from a patient with RTD Type 3 revealed signs of a motor neuronopathy and axonal degeneration (Johnson et al. 2010).
Generally atrophy of type 1 and 2 muscle fibers with no light microscopic evidence of mitochondrial myopathy.
Nimmo et al. 2017 recently reported on two patients, with RTD Type 2 and 3, whose clinical and biochemical features mimicked mitochondrial myopathy. Muscle biopsies in these patients revealed complex II deficiency in the patient with RTD Type 2 and combined complex II + III deficiency in the patient with RTD Type 3. Ragged red fibers consistent with mitochondrial myopathy were found in both patients. The authors suggested RTD should be included into the differential diagnosis of mitochondrial myopathy and complex II deficiency.
Foley AR, Menezes MP, Pandraud A et al (2014) Treatable childhood neuronopathy caused by mutations in riboflavin transporter RFVT2. Brain 137:44–56
Johnson JO, Gibbs JR, VanMaldergem L et al (2010) Exome sequencing in Brown-Vialetto-van Laere syndrome. Am J Hum Genet 87:567–9, author reply 569–70
Nimmo GA, Ejaz R, Cordeiro D, et al (2017) Riboflavin transporter deficiency mimicking mitochondrial myopathy caused by complex II deficiency.Am J Med Genet. 2017;1–5.