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Refsum disease

Refsum disease, also known as “heredopathia atactica polyneuritiformis” is a rare neurological disease characterized biochemically by accumulation of phytanic acid in blood plasma and tissues, including fat and neurons.

Refsum disease, also known as “heredopathia atactica polyneuritiformis” is a rare neurological disease characterized biochemically by accumulation of phytanic acid in blood plasma and tissues, including fat and neurons.

  • Autosomal recessive inheritance

Etiopathogenesis

Adult Refsum disease 1

  • Mutations in the phytanoyl-CoA hydroxylase (PAHX aka PHYH) gene, on the PHYH locus at 10p13 on chromosome 6q22-24

Adult Refsum disease 2

  • Mutations in the peroxin 7 (PEX7) gene on chromosome 6q22-24

Disorder of α-oxidation

Phytanic acid not metabolized to pristanic acid

Phytanic acid accumulation


Presentation

Childhood/adolescence-onset with a progressive course, with periods of stagnation/remission

  • Ophthalmic involvement:
    • Atypical retinitis pigmentosa (earliest sign)
    • Cataracts
    • Night blindness
  • Otologic involvement:
    • Severe sensorineural deafness (80% cases)
  • Neurologic damage:
    • Mental and growth retardation
    • Ichthyosis (scaly skin)
    • Peripheral neuropathy
    • Anosmia
  • Cerebellar ataxia (late onset)
  • Facial dysmorphism
  • Hepatomegaly
  • Shortening of 4th toe
Refsum's disease in an Arabian patient. Symmetric short fourth toes (arrow).
Refsum’s disease in an Arabian patient. Symmetric short fourth toes (arrow). | FERTL, E., FÖLDY, D., VASS, K., AUFF, E., VASS, C., MOLZER, B., & BERNHEIMER, H. (2001). Refsum’s disease in an Arabian family. Journal of Neurology, Neurosurgery &Amp; Psychiatry, 70(4), 564 LP-565. Retrieved from http://jnnp.bmj.com/content/70/4/564.abstract

Diagnosis

CSF analysis:

  • ↑ CSF proteins

Skin biopsy:

Presence of cells in the basal and suprabasal layers of the epidermis containing variably sized vacuoles with accumulated lipids (PATHOGNOMIC)
  • Hyperkeratosis
  • Hypergranulosis
  • Acanthosis

Differential diagnosis:

  • Usher syndromes (types 1, 2, and 3)
  • Alström syndrome
  • Kearns-Sayre syndrome
  • Sjögren-Larsson syndrome

Management

Lifestyle changes

  • Phytanic acid-restricted diet
    • Avoid the consumption of fats from ruminant animals and certain fish, such as tuna, cod, and haddoc

Medical management

  • Plasmapheresis

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