Identification of novel pathogenic variants in the PHYH gene and extending the phenotypic range in Refsum disease.

PURPOSE: Two patients with a suspected inherited retinal dystrophy (IRD) were referred to a specialist ophthalmology clinic for genetic testing to determine the cause of their disease.

CASE REPORT: A 50-year-old female patient (P1) presented with retinitis pigmentosa and poor vision since childhood. Molecular genetic testing in P1 revealed two novel pathogenic variants in PHYH (NM_006214.4): p.(Val93*) and p.(Asn71Ilefs*23). A 57-year-old male patient (P2) presented with pigmentary changes at the macula. Molecular genetic testing in P2 revealed two novel variants in PHYN: p.(Phe183Ser) and c.2461G>C (splice acceptor). Both patients were referred to the metabolic disease clinic and phytanic acid levels were found to be 256 µg/mL in P1 (normal is < 3 µg/mL) and 48.2 µmol/L in P2 (normal is < 2.2 µmol/L) confirming the diagnosis of Refsum disease. Both patients shared systemic features of the disease including bilaterally abnormal metatarsals and dry skin, while P1 also had characteristic anosmia, kidney disease, peripheral neuropathy and mild hearing impairment.

CONCLUSION

We document for the first time an association between macular dystrophy and Refsum disease. Early diagnosis is important so that diet can be modified to improve prognosis for the complications associated with Refsum disease, although improvements in vision, slowing the retinal degeneration and overcoming refractory miosis, are less achievable.