From the Research
ITPR3 mutations are associated with Charcot-Marie-Tooth disease type 1-J (CMT1J), a rare subtype of this inherited peripheral neuropathy, and currently, there is no specific treatment targeting ITPR3 in CMT1J, with management focusing on supportive care, including physical therapy, orthotic devices, and pain management, as recommended by the most recent clinical practice guideline for the management of paediatric Charcot-Marie-Tooth disease 1. The ITPR3 gene encodes the inositol 1,4,5-trisphosphate receptor type 3, which plays a crucial role in calcium signaling within cells. In CMT1J, mutations in ITPR3 lead to altered calcium homeostasis in Schwann cells, the cells that produce myelin in the peripheral nervous system. This disruption in calcium signaling results in impaired myelination and axonal degeneration, causing the characteristic symptoms of CMT, such as muscle weakness, sensory loss, and foot deformities. Some key points to consider in the management of CMT1J include:
- The importance of a multidisciplinary approach to care, including genetic counselors, physical and occupational therapists, physiatrists, orthotists, mental health providers, and community resources 2
- The use of comprehensive genetic testing, including next-generation sequencing, to establish a definitive molecular diagnosis and guide management decisions 3
- The need for ongoing research into the development of targeted therapies aimed at modulating calcium signaling or preserving Schwann cell function, as well as the evaluation of treatment efficiency and long-term safety 4
- The importance of maximizing functional independence and quality of life, while minimizing disability and secondary morbidity, through the use of supportive care and rehabilitative strategies 5