Genomic coordinate (human 10:13,277,799 PHYH) & (mouse 2:4,923,830 Phyh).
Cytoband (human 10p13 PHYH) & (mouse 2qA1 Phyh).
Here I present: “Adult Refsum Disease”, Victor McKusick, Mendelian Inheritance in Man’, 1966. (PHYH) icd10=E71.3
INTRODUCTION.
Adult Refsum disease is an autosomal recessive inborn error of lipid metabolism classically characterized by a tetrad of clinical abnormalities: retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated protein levels in the cerebrospinal fluid (CSF) without an increase in the number of cells. However, not all patients show all these features. All patients have accumulation of an unusual branched-chain fatty acid, phytanic acid, in blood and tissues. Other variable features include cardiac dysfunction, nerve deafness, ichthyosis, and multiple epiphyseal dysplasia.
Adult Refsum Disease (Classic Refsum Disease)
Cause:
Defect in α-oxidation of phytanic acid.
Usually PHYH (phytanoyl-CoA hydroxylase)
Less commonly PEX7
Biochemistry’
↑ phytanic acid
Normal or mildly abnormal very-long-chain fatty acids (VLCFA)
Onset:
Adolescence to adulthood
Key Clinical Features:
Retinitis pigmentosa (often first)
Peripheral neuropathy
Cerebellar ataxia
Sensorineural hearing loss
Anosmia
Ichthyosis
Cardiac arrhythmias (phytanic acid toxicity)
Cognition
Usually normal
Inheritance
Autosomal recessive
ICD-10=E71.3
Treatment:
Dietary restriction of phytanic acid
Avoid dairy fat, ruminant meat, some fish
Plasmapheresis for acute crises
Symptoms can improve or stabilize.
There is evidence that classic Refsum disease is caused by mutation in the phytanoyl-CoA hydroxylase (PHYH) gene encoded on genomic coordinate 10:13,277,799 and cytoband 10p13 in humans.
