Peripheral Neuropathy in Alport Syndrome

Clinical Presentation and Diagnosis

The American College of Physicians recommends assessing patients with Alport syndrome for peripheral neuropathy, which can present with distal symmetric sensory symptoms including numbness, paresthesias, tingling, and burning sensations 2, 3
The European Neurological Society suggests that large fiber neuropathy can cause numbness and loss of proprioception, while small fiber sensory polyneuropathy typically presents with pain, numbness, and autonomic dysfunction 4
The assessment of neuropathy should include testing of small-fiber function (pinprick and temperature sensation) and large-fiber function (vibration perception and 10-g monofilament), with a strength of evidence rated as high for the use of these tests in diagnosing peripheral neuropathy 4, 5

The American Academy of Neurology recommends considering ulnar nerve entrapment (bilateral) as a less common cause of bilateral ulnar nerve distribution numbness, which would require nerve conduction studies to differentiate from polyneuropathy 2, 3
The National Kidney Foundation suggests that uremic neuropathy from progressive renal insufficiency in Alport syndrome should be considered as a potential cause of peripheral neuropathy, with a strength of evidence rated as moderate for the association between chronic kidney disease and peripheral neuropathy 4

The American Association of Neuromuscular and Electrodiagnostic Medicine recommends performing electromyography with nerve conduction studies to identify the pattern of neuropathy (axonal vs. demyelinating, mononeuropathy vs. polyneuropathy), with a strength of evidence rated as high for the use of these tests in diagnosing peripheral neuropathy 3
The National Institute of Diabetes and Digestive and Kidney Diseases suggests assessing renal function, including creatinine, eGFR, and urinalysis, to determine if uremic neuropathy is contributing, with a strength of evidence rated as moderate for the association between chronic kidney disease and peripheral neuropathy 4
The American College of Physicians recommends screening for alternative causes of neuropathy, including vitamin B12 deficiency, thyroid function (hypothyroidism), diabetes screening (glucose, HbA1c), toxin exposure (including alcohol), and neurotoxic medications, with a strength of evidence rated as high for the importance of identifying and treating these conditions 4

The European Renal Association recommends optimizing renal function management with ACE inhibitors or ARBs, which are the mainstay of slowing Alport syndrome progression, although this is not directly related to the management of peripheral neuropathy 4
The American Academy of Neurology suggests using symptomatic treatment for neuropathic pain, such as duloxetine (60-120 mg/day), which has shown efficacy for diabetic peripheral neuropathy, with a strength of evidence rated as moderate for the use of this medication in treating neuropathic pain 4
The American College of Physicians recommends addressing any identified reversible causes, such as vitamin deficiencies or metabolic abnormalities, and monitoring for progression with serial neurological examinations and repeat nerve conduction studies if symptoms worsen, with a strength of evidence rated as high for the importance of ongoing monitoring and treatment adjustment 3, 4