skeletal malformations

Refsum Disease, Adult

Clinical Characteristics
Ocular Features: 

A retinitis pigmentosa-like retinopathy is the major ocular manifestation of this disease.  There is typical night blindness and visual field constriction.   Rod ERG responses are usually subnormal.  However, central acuity is also reduced due to a degenerative maculopathy.   Cataracts and optic atrophy are common.  The macula may undergo progressive degeneration and optic atrophy is not uncommon.  Some patients have defective pupillary responses.

Systemic Features: 

Onset of symptoms is usually late in the first decade and sometimes into the third decade.  There is usually a polyneuropathy with impaired motor reflexes and paresis in the limbs.  A progressive sensorineural hearing loss occurs in many patients.  Sensory deficits also occur.  Some have ataxia and skin changes of ichthyosis.  Anosmia is a near universal feature.  Heart failure may occur and cardiac abnormalities such as conduction defects can occur.  A variety of skeletal abnormalities such as pes cavus, short fourth metatarsals, and evidence of epiphyseal dysplasia have been reported.  There is considerable clinical heterogeneity even within families.

Phytanic acid oxidase activity as measured in fibroblasts is often low while serum phytanic acid is increased.  The cerebrospinal fluid contains increased protein but no increase in cells.


This disorder results from mutations in the PHYH (PAHX) gene (10pter-p11.2) encoding phytanoyl-CoA hydroxylase, or, more rarely in PEX7 (6q22-q24) encoding peroxin-7 resulting in an uncommon condition (10% of cases) sometimes called adult Refsum disease-2. 

Mutations in the latter gene also cause rhizomelic chondrodysplasia punctata type 1 (215100) which does not have all of the neurological features or the retinopathy.

There is also so-called infantile form of Refsum disease (266510).

Autosomal recessive
Treatment Options: 

A diet low in phytanic acid can lead to improvement in the neurologic symptoms such as the ataxia and polyneuropathy but must be instituted in early stages of the disease.  This approach may not be as beneficial for the visual or auditory symptoms.

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