Infantile Refsum disease (IRD)
General description
Infantile Refsum disease (IRD) represents a complex peroxisomal biogenesis disorder that, despite sharing a similar name with adult Refsum disease, constitutes a distinct clinical entity with unique pathophysiological mechanisms and clinical presentations.
Infantile Refsum disease belongs to the Zellweger spectrum of peroxisome biogenesis disorders (PBD-ZSS), representing the mildest variant within this continuum of conditions that also includes Zellweger syndrome and neonatal adrenoleukodystrophy. The disease results from mutations in any of thirteen known PEX genes that encode peroxins, essential proteins required for normal peroxisome assembly and function. These genetic defects lead to abnormal peroxisome biogenesis, resulting in multiple peroxisomal enzyme deficiencies and subsequent metabolic dysfunction.
Infantile Refsum Disease presents with a characteristic constellation of clinical features that typically manifest from birth or early infancy, though the subtle nature of initial symptoms may delay diagnosis until adulthood in some cases.
Early infantile symptoms include nystagmus, hypotonia, sensorineural hearing loss, growth retardation, mild facial dysmorphism, and hepatomegaly. Hepatic dysfunction initially presents with neonatal jaundice and may progress to episodes of intracranial bleeding due to coagulopathy. The ophthalmological manifestations are particularly prominent, featuring progressive retinitis pigmentosa that often leads to significant visual impairment or blindness, frequently accompanied by characteristic fundal changes that may include atypical nummular patches of hypopigmentation.
During childhood, patients develop progressive developmental deficits alongside persistent hypotonia, though most achieve motor milestones, albeit with significant delays. Communication abilities are typically limited to a few words or signs. The hearing impairment progresses from initial sensorineural deficits to deafness by early childhood. Additional complications that may emerge include osteoporosis and fractures in less mobile patients, adrenal insufficiency, and renal calcium oxalate stones in older children.
References
- Choksi, Vaishali, et al. "Infantile refsum disease: case report." American journal of neuroradiology 24.10 (2003): 2082-2084.
T2WI and FLAIR hyperintensity
MRI reveals characteristic abnormalities including symmetrical signal intensity changes in cerebellar dentate nuclei and corticospinal tract spanning from the upper pons to internal capsules. MRI also shows progressive leukoencephalopathy affecting periventricular white matter.