The finding was described in a case report published in the journal Neuropathology, titled “A novel mutation in PRPS1 gene causes X‐linked Charcot‐Marie‐Tooth disease‐5.“
The subject of the case report was male and was 13 years old at the time of publication. The researchers who presented the case report first described the patient’s development: starting at about age 3, the patient was found to have hearing loss, which was managed with a hearing aid. At the same age, the patient had difficulty walking, with frequent falls, because of dropped feet.
By age 7, the patient was experiencing muscle weakness that made it difficult for him to stand or squat; this got worse over the next several years and included loss of sensation and muscle atrophy in the hands and feet.
The researchers performed a nerve biopsy, which revealed a lower-than-normal density of myelinated fibers — fewer neurons coated in myelin, the “sheath” that protects neurons. There was also evidence of neurons degenerating.
Further assessment revealed decreased activity in nerves related to hearing and sight, although the patient’s vision was not impaired (impaired vision is a common symptom of CMTX5). The researchers therefore suggested that optic (eye) involvement was sub-clinical (present but not resulting in symptoms). They noted, “Optic neuropathy [nerve disease] should be followed up in the course of the condition.”
Genetic testing was performed on the patient and a mutation (c.334G>C) in PRPS1 was identified. Notably, because the patient was male, and PRPS1 is located on the X chromosome, this was the only copy of PRPS1 present (males have one X chromosome and one Y chromosome, whereas females have two X chromosomes).
Additional genetic testing of 500 unaffected Chinese individuals did not reveal anyone with this mutation, supporting the idea that it could be disease-causing. Although neither of the patient’s biological parents showed similar symptoms. The patient’s biological mother was found to have one copy of the PRPS1 gene with the same mutation, whereas the other copy did not have this mutation (because the mother had two X chromosomes, there were two copies of PRPS1).
Computer-based simulations predicted that the identified mutation would disrupt the normal function of the PRPS1 protein, and indeed, when the researchers tested the activity of the PRPS1 protein in the patient’s blood, they found close to no activity. PRPS1 activity in the patient’s mother was slightly lower than normal; presumably, the presence of one non-mutated gene could functionally compensate for the mutated gene.
Based on all these findings, the researcher diagnosed the patient with CMTX5, writing, “Except for the visual acuity loss, the main symptoms, as well as genetic and enzymatical findings in the present patient, were consistent with the features of CMTX5.”
They added, “To the best of our knowledge, this is the first report of PRPS1-related CMTX5 in a Chinese population.”