A novel Refsum-like disorder that maps to chromosome 20

Area of Science:

• Genetics
• Neurology
• Rare Diseases

Background:

• Refsum disease is a rare genetic disorder characterized by the accumulation of phytanic acid.
• A consanguineous Norwegian family presented with a neurologic disorder clinically resembling Refsum disease.

Purpose of the Study:

• To clinically and genetically characterize a novel neurologic disorder in a Norwegian family.
• To differentiate this disorder from Refsum disease and identify its genetic basis.

Main Methods:

• Clinical evaluation of affected individuals (brother, sister, third cousin).
• Genealogic studies to establish consanguinity.
• Homozygosity mapping to identify the disease locus on chromosome 20.
• Exclusion of Refsum disease by normal phytanic and pristanic acid levels and alpha-oxidation enzyme activity.

Main Results:

• A slowly progressive neurologic disorder starting in childhood with peripheral neuropathy, hearing loss, cataracts, ataxia, spasticity, and pigment retinopathy.
• The disease locus was mapped to a 15.96 Mb region on chromosome 20 (20p11.21-q12).
• No detrimental sequence variants were found in 23 candidate genes.

Conclusions:

• The clinical spectrum of disorders resembling Refsum disease is more heterogeneous than previously understood.
• This novel disorder requires further investigation for precise genetic identification.
• Reporting these findings may facilitate the identification of other affected families.