Infantile Refsum’s disease:
A misnamed peroxisomal disorder

It must be noted that there is much confusion in the way peroxisomal disorders are named. Many doctors use the name Zellweger’s syndrome to designate all generalized peroxisomal disorders. In the opposite extreme, more often doctors tend to diagnose all peroxisomal patients with infantile Refsum’s disease (IRD), the less severe clinical form or phenotype. In the middle, there are patients with neonatal adrenoleukodystrophy (NALD), a peroxisomal disorder of intermediate severity and often undistinguished from infantile Refsum's disease. Quite often, even the word infantile is deleted and the patient’s diagnosis is confused with Refsum’s disease, an altogether different disorder of the adult. Refsum’s disease is not a generalized peroxisomal disorder but an isolated enzyme defect. This is a confusion that should be avoided since it generates misunderstanding among doctors and parents. For the moment, it has not been found any clear correlation between the gene defect (genotype) and the phenotype. So while we do not have a better genetic base to distinguish the different clinical pictures, it is better to simply call them classic Zellweger’s syndrome (the most severe disease) and generalized peroxisomal disorders, without distinction between NALD and IRD. Indeed, some misnamed IRD patients who survive the first years of life will later develop signs characteristic of NALD, such as adrenal insufficiency and demyelination.