Progressive polyradiculoneuropathy due to intraneural oxalate deposition in type 1 primary hyperoxaluria

Abstract

Introduction A 24 year old man with primary hyperoxaluria type 1 (PH1) presented with a rapidly progressive axonal and demyelinating sensorimotor polyradiculoneuropathy shortly after the onset of end stage renal disease. His plasma oxalate level was markedly elevated at 107 µmol/L (normal: <1.8 µmol/L). Methods A sural nerve biopsy was performed. Teased fiber, paraffin and epoxy sections, and morphometric procedures were performed on this sample and on an archived sample from a 22 year old man as an age- and gender-matched control. Embedded teased fiber electron microscopy was also performed. Results The biopsy revealed secondary demyelination and axonal degeneration. Under polarizing light, multiple bright hexagonal, rectangular, and starburst inclusions typical of calcium oxalate monohydrate crystals were seen1,2,3. Discussion Proposed mechanisms of nerve damage include disruption of axonal transport due to crystal deposition, toxic effect of oxalate, or nerve ischemia related to vessel occlusion from oxalate crystal deposition.

Natural History of Clinical, Laboratory, and Echocardiographic Parameters of a Primary Hyperoxaluria Cohort on Long Term Hemodialysis

“…The current study demonstrates that clinically evident manifestations of oxalate on bone, skin, nervous system, and eyes vary from patient to patient over time on dialysis (13)(14)(15)(16)(17)(18). Due to our small sample size and retrospective review of clinicallyindicated testing for oxalosis, we cannot draw statistically significant conclusions regarding prevalence.…”

Neuroprotective Effects and Therapeutic Potential of Dichloroacetate: Targeting Metabolic Disorders in Nervous System Diseases

“… 189 , 190 Oxalate is considered relevant to peripheral neuropathy, and its metabolism consumes thiamine. 191 , 192 In addition, thiamine is a cofactor of pyruvate dehydrogenase. 193 After 7 weeks of DCA (1.1 g/kg) treatment in rats, oxalate in the urine was 86% higher in rats treated with DCA than in controls but was only 28% higher in those treated with DCA plus thiamine than in controls; thus, DCA may lead to peripheral neuropathy due to thiamine deficiency and oxalate accumulation.…”

Inherited Neuromuscular Disorders: Which Role for Serum Biomarkers?

“…Type 1 hyperoxaluria (PH1) is a rare autosomal recessive disease due to mutation in the alanine-glyoxalate aminotransferase gene leading to glyoxylate accumulation and its conversion to oxalate with calcium oxalate crystals deposition in various tissues [ 177 ]. The biochemical hallmarks of PH1 are hyperoxaluria with or without hyperglycolaturia; hence, 24 h urine collection measuring oxalate, creatinine and glycolate is recommended.…”