[Clinical symptoms of generalized peroxisomal disorders]

In generalized peroxisomal disorders, the clinical picture is not always obvious enough to orientate the diagnosis at an early stage of the disease. Although classic Zellweger syndrome can seldom be misdiagnosed, unless we ignore this kind of pathology altogether, the other phenotypes (neonatal adrenoleukodystrophy and infantile Refsum disease) are not always clearly delineated. Above all, the diagnosis may be difficult if we expect the patient to closely correspond to the cerebro-hepato-renal syndrome prototype.

Thus, we must establish a series of crucial signs and symptoms that, taken together, make us suspect a peroxisomal disease and order the corresponding biochemical screening. In our experience, craniofacial dysmorphia may be misleading in the less severe phenotypes and is probably the most subjective feature. In contrast, an infant with widely open fontanels and axial hypotonia, in special if failure to thrive and/or hepatomegaly are associated, must be considered suspicious enough to make us think of a peroxisomal disorder and perform a metabolic screening. Later on in life, the neurological picture and psychomotor delay become more and more clear, and sensorineural blindness and deafness are virtually constant.