Molecular basis of Refsum disease: sequence variations in phytanoyl-CoA hydroxylase (PHYH) and the PTS2 receptor (PEX7)

Hum Mutat. 2004 Mar;23(3):209-18. doi: 10.1002/humu.10315.


Refsum disease has long been known to be an inherited disorder of lipid metabolism characterized by the accumulation of phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) caused by an alpha-oxidation deficiency of this branched chain fatty acid in peroxisomes. The mechanism of phytanic acid alpha-oxidation and the enzymes involved had long remained mysterious, but they have been resolved in recent years. This has led to the resolution of the molecular basis of Refsum disease. Interestingly, Refsum disease is genetically heterogeneous; two genes, PHYH (also named PAHX) and PEX7, have been identified to cause Refsum disease, as reviewed in this work.

Publication types

  • Review

MeSH terms

  • Animals
  • Base Sequence / genetics
  • Gene Duplication
  • Genetic Variation / genetics*
  • Humans
  • Mixed Function Oxygenases / genetics*
  • Molecular Sequence Data
  • Mutation, Missense / genetics
  • Peroxisomal Targeting Signal 2 Receptor
  • Phenotype
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Refsum Disease / genetics*
  • Sequence Deletion / genetics


  • PEX7 protein, human
  • Peroxisomal Targeting Signal 2 Receptor
  • Receptors, Cytoplasmic and Nuclear
  • Mixed Function Oxygenases
  • PHYH protein, human

Associated data

  • GENBANK/AF242379
  • GENBANK/AF242380
  • GENBANK/AF242381
  • GENBANK/AF242382
  • GENBANK/AF242383
  • GENBANK/AF242384
  • GENBANK/AF242385
  • GENBANK/AF242386
  • OMIM/266500
  • OMIM/601757
  • OMIM/602026
  • RefSeq/NM_000288
  • RefSeq/NM_006214