Refsum's Disease

NeuroLearn NeuroHelp Metabolic @ Peroxisomal disorders, classification

Background    Gross Pathology    Histopathology & Immunohistochemistry  

BACKGROUND AND CLINICAL INFORMATION: Head  

Spectrum: Zellweger syndrome, neonatal adrenoleukodystrophy (NALD), and Infantile Refsum’s disease constitute a disease continuum of peroxisomal disorders. Migration disorders, can be seen in both Zellweger syndrome and, less severely, in NALD. No malformation has been reported in infantile Refsum’s disease.  

Biochemistry: This is an autosomal recessive disorder due to phytanic acid acid oxidase deficiency. Phytanic acid accumulates in serum and a variety of tissues.

Clinical manifestations: 

• In contrast to other peroxisomal disorders, the principal manifestation of Refsum’s disease is in peripheral nerves. 

• Clinical manifestations start in the 2^nd and 3^rd decade. The salient clinical feature is chronic distal symmetrical sensorimotor neuropathy of variable onset.  Some patients have progressive symptomrs and others may have relapsing remitting symptoms. There are also ataxia, blindness, sensorineural deafness, anosmia, ichthyosis and cardiomyopathy. 

• Patients usually die in their middle age years. 

• CSF may show a modest elevation of protein but not in cells.

GROSS PATHOLOGY: Head  

Peripheral nerves including peripheral nerve roots are enlarged; enlargement is maximal in proximal regions and most prominent in limb girdles.

HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY: Head  

Retina: Pigmentary retinal degeneration.

Peripheral nerve pathology:

• Increase in perineurial and interstitial connective tissue.

• Reduced in number of myelinated and unmyelinated axons with onion-bulb formation admixed with interspersed collagen fibers.

• No inflammation.

EM: Densely osmophilic homogeneous inclusions in the cytoplasm of Schwann cells. Lattice like crystalloid structures in abnormal mitochondria of Schwann cells; these crystalloid structures are not specific for Refums disease.

NeuroLearn NeuroHelp Metabolic For Comment: KarMing-Fung@ouhsc.edu

Background    Gross Pathology    Histopathology & Immunohistochemistry