ABSTRACT
Introduction: Charcot-Marie-Tooth (CMT) is a group of inherited neuromuscular disorders that vary clinically and genetically. It is characterized by peripheral nerve damage, leading to muscle weakness and sensory loss. Case presentation: A 13-year-old male presented to the rheumatology department with bilateral hearing impairment since the age of 3 years, pes cavus, and difficulties walking. Some family members had Achilles tendon lengthening surgery. During physical examination, the patient had a shortened Achilles tendon, there are high arches in the feet, curled toes, loss of touch sensation in the feet, ankles, and legs, atrophy in the foot muscles. An eye examination revealed a discrepancy that needed glasses. Neurological findings included horizontal and vertical nystagmus, proprioception disorder, and demyelinating sensorimotor disorder diagnosed as CMT type 1. The audiogram showed bilateral sensorineural hearing impairment. MRI revealed spinal disc bulges. The treatment plan includes Achilles tendon lengthening surgery and physical therapy. Clinical discussion: CMT patients need to receive supportive treatment including physical therapy, hearing aids, and glasses, to help improve their quality of life. Conclusion: CMT disease is a genetic disorder that causes difficulties in movement, coordination, and daily activities due to muscle weakness and sensory impairments. In a few cases, patients have been documented to have bilateral hearing impairment as their first symptoms. It affects individuals in Syria and around the world, and requires proper diagnosis and treatment.
ABSTRACT
BACKGROUND: The complement system is a key player in innate immunity and a modulator of the adaptive immune system. Among the three pathways of complement, the alternative pathway (AP) accounts for most of the complement activation. Factor B (FB) is a major protease of the AP, making it a promising target to inhibit the AP activity in conditions of uncontrolled complement activation. METHODS: Based on the data obtained from sequence analysis and conformational changes associated with FB, we expressed and purified a recombinant FB fragment (FBfr). We tested the inhibitory activity of the protein against the AP by in vitro assays. RESULTS: FBfr protein was proven to inhibit the complement AP activity when tested by C3b deposition assay and rabbit erythrocyte hemolytic assay. CONCLUSION: Our recombinant FBfr was able to compete with the native human FB, which allowed it to inhibit the AP activity. This novel compound is a good candidate for further characterization and testing to be used in complement diagnostic tests and as a drug lead in the field of complement therapeutics.
