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 and paraffin and epoxy sections were done 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 polarized light, multiple bright hexagonal, rectangular, and starburst inclusions, typical of calcium oxalate monohydrate crystals, were seen.

Conclusions: The 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.

Keywords: crystalline neuropathy; nerve pathology; peripheral neuropathy; primary hyperoxaluria type 1; renal failure.

Figure 1

Teased fiber preparation of sural nerve: Calcium oxalate monohydrate crystals are noted by arrows on panel A under standard light and are clearly visible on panel B under polarized light. Note the associated perinodal demyelination.

Figure 2

Methyl violet preparation: Two starburst crystals are noted adjacent to an epineurial blood vessel. Panels B and D are under polarized light.

Figure 3

Epoxy sections stained with methylene blue reveal multifocal fiber loss, prominent axonal degeneration (arrow), and calcium oxalate crystals within nerve fibers (box). Panel B is under polarized light.

Figure 4

Electron microscopy along the course of an individual plastic embedded teased nerve fiber reveals a calcium oxalate monohydrate crystal within nerve myelin just outside of the axolemma. In box A the arrow points to a crystal under polarized light on a single teased fiber. In box B the arrow points to that calcium oxalate crystal on an epoxy section stained with methylene blue.