Overview
Axonal neuropathy involves damage to the axons of peripheral nerves, leading to motor and sensory deficits. It can result from various etiologies including genetic mutations, nutritional deficiencies, and toxic exposures 124.Diagnosis
Clinical Presentation: Early onset axonal sensorimotor polyneuropathy with symptoms like sensory loss, motor weakness, and reflex changes 1.
Electrophysiological Studies: Nerve conduction studies often show axonal degeneration with reduced amplitude and normal or slightly slowed conduction velocities 2.
Genetic Testing: Whole exome sequencing to identify mutations in genes like SLC5A6 1.
Laboratory Tests: Assess micronutrient levels (thiamine, vitamin B12) to rule out nutritional deficiencies 2.
Toxic Exposure Screening: Evaluate for potential toxic exposures such as acetone and 2,5-hexanedione 4.Management
Nutritional Supplementation: Replenishment with biotin, lipoic acid, and pantothenic acid for SLC5A6-related deficiencies 1.
Intravenous Immunoglobulin (IVIG): Effective for chronic relapsing axonal neuropathy 3.
Specific Micronutrient Therapy: Address deficiencies identified in ANAN, particularly thiamine and vitamin B12 2.
Toxic Exposure Management: Avoidance and supportive care for toxic exposures like acetone and 2,5-hexanedione 4.Special Populations
Pediatrics: SLC5A6 mutations can present in childhood with biotin-responsive neuropathy 1.
Elderly: Chronic relapsing axonal neuropathy can occur and respond to IVIG 3.Key Recommendations
Genetic Testing for SLC5A6 Mutations in patients with early-onset axonal sensorimotor polyneuropathy to guide specific multivitamin therapy (Evidence: Moderate 1).
Evaluate and Correct Micronutrient Deficiencies (thiamine, vitamin B12) in patients with suspected nutritional axonal neuropathy (Evidence: Moderate 2).
Consider IVIG Therapy for chronic relapsing axonal neuropathy unresponsive to other treatments (Evidence: Weak 3).References
1 Pi BK, Lee AJ, Nam SH, Chung KW, Choi BO. SLC5A6 Mutations in Axonal Sensorimotor Polyneuropathy Patients Concurrent With Sodium Dependent Multivitamin Transporter Deficiency and Improved Effects by Multivitamin Therapy. Journal of the peripheral nervous system : JPNS 2025. link
2 Hamel JI, Logigian EL. Clinical Spectrum and Prognosis in Patients With Acute Nutritional Axonal Neuropathy. Neurology 2023. link
3 Katirji B. Chronic relapsing axonal neuropathy responsive to intravenous immunoglobulin. Neurology 1997. link
4 Ladefoged O, Perbellini L. Acetone-induced changes in the toxicokinetics of 2,5-hexanedione in rabbits. Scandinavian journal of work, environment & health 1986. link