Information for clinicians
2a Clinical diagnosis
Adult Refsum's disease (ARD) is suspected in individuals with late childhood-onset retinitis pigmentosa and variable combinations (in decreasing order of frequency) of the following manifestations:
- Sensory motor neuropathy
- Hearing loss
- Short metacarpals and metatarsals present from birth in about 35% of individuals with ARD
- Cardiac arrhythmias
Note: The full constellation of signs is rarely seen in an individual. Neuropathy and ataxia are present in about 50% of individuals, but usually manifest after childhood.
Figure 2.1 Cumulative incidence of clinical features on presentation of 15 patients with adult Refsum's disease. (RP= retinitis pigmentosa.)
2b Differential Diagnosis
2b(i) a-Methylacyl-CoA racemase (AMACR) deficiency (OMIM 604489)
This enzyme deficiency leads to an ARD-like condition but is accompanied by high plasma concentrations of pristanic acid and the C27-bile-acid intermediates, whereas the plasma phytanic acid concentration is low. The phenotype is one of adult-onset sensory motor neuropathy with or without associated pigmentary retinopathy [Ferdinandusse et al 2000].
2b(ii) Retinitis pigmentosa
Since visual deterioration is almost always the first symptom of adult Refsum's disease, plasma phytanic acid concentration should be measured in any individual with retinitis pigmentosa, especially when combined with other features, including anosmia and impaired hearing. (See also the GeneReview: Retinitis Pigmentosa Overview.)
2b(iii) Retinitis pigmentosa and sensorineural hearing loss
- Usher syndrome type 1 is characterized by a congenital, bilateral, profound sensorineural hearing loss, vestibular areflexia, and adolescent-onset retinitis pigmentosa. Inheritance is autosomal recessive.
- Usher syndrome type 2 is characterized by congenital, bilateral, sensorineural hearing loss predominantly in the higher frequencies that ranges from mild to severe; normal vestibular function; and adolescent-to-adult onset of retinitis pigmentosa. Inheritance is autosomal recessive.
- Usher syndrome type 3 is characterized by progressive sensorineural hearing loss and adolescent-onset retinitis pigmentosa. Inheritance is autosomal recessive.
- Alström syndrome is characterized by cone-rod dystrophy, obesity, progressive sensorineural hearing impairment, dilated cardiomyopathy, insulin resistance, and developmental delay. Inheritance is autosomal recessive.
- Kearns-Sayre syndrome (see Mitochondrial Deletion Syndromes). Kearns-Sayre syndrome (KSS) is defined by the triad of onset before age 20 years, pigmentary retinopathy, and progressive external ophthalmoplegia (PEO). In addition, affected individuals have at least one of the following: cardiac conduction block, cerebrospinal fluid protein concentration greater than 100 mg/dl, or cerebellar ataxia. Sensorineural hearing loss is seen in almost all affected individuals. Kearns-Sayre syndrome is due to deletion of mitochondrial DNA (mtDNA).
Friedreich ataxia is characterized by slowly progressive ataxia with onset usually before the age of 25 years typically associated with depressed tendon reflexes, dysarthria, Babinski responses, and loss of position and vibration senses. Hearing loss is uncommon. Inheritance is autosomal recessive. (See also the GeneReview: Ataxia Overview.)
Sjögren-Larsson syndrome is characterized by congenital ichthyosis and onset of ataxia in early childhood.
2b(vi) Increased CSF protein concentration
High CSF protein concentrations can be found in a variety of conditions.
Page last updated 26 June 2006