General description

Refsum disease is a recessive disorder characterized by defective peroxisomal alpha-oxidation of phytanic acid, leading to its accumulation in blood and tissues. The condition results from mutations in either the phytanoyl-CoA hydroxylase (PHYH) gene located on chromosome 10p13 (accounting for more than 90% of cases) or the PTS2 receptor (PEX7) gene located on 6q23.3. In patients with Refsum disease, phytanic acid levels are markedly elevated (10-50 mg/dL compared to normal values of ≤0.2 mg/dL) and account for 5-30% of serum lipids.

The most common and early symptom is retinitis pigmentosa, which often begins with night blindness and progressively leads to concentric visual field constriction and eventual vision loss. Other ophthalmologic findings include small pupils, ptosis, nystagmus, cataracts, and abnormal pupillary reflexes.

Neurological symptoms are prominent and include chronic progressive polyneuropathy, which starts in the distal lower limbs and spreads to the hands, causing weakness, muscle atrophy, sensory impairment, and pain. Cerebellar ataxia is another key feature, leading to difficulties with walking, intention tremors, and nystagmus. Hearing loss and anosmia are also frequently observed.

Cardiac involvement is significant, with abnormalities such as cardiomyopathy, tachycardia, conduction disturbances, and fatal arrhythmias, which can result in sudden death if untreated. Additionally, some patients develop dermatological conditions like ichthyosis, as well as skeletal deformities such as pes cavus and hammer toes.

The onset of Refsum disease varies widely, from early infancy to late adulthood, with no strict correlation between age of onset and severity. Diagnosis is often delayed, particularly in childhood, as early symptoms such as night blindness may go unnoticed.

References

1. Wierzbicki, Anthony S., et al. "Refsum's disease: a peroxisomal disorder affecting phytanic acid α‐oxidation." Journal of neurochemistry 80.5 (2002): 727-735.
2. Choksi, Vaishali, et al. "Infantile refsum disease: case report." American journal of neuroradiology 24.10 (2003): 2082-2084.
3. Bompaire, Flavie, et al. "Refsum disease presenting with a late-onset leukodystrophy." JIMD Reports, Volume 19 (2015): 7-10.