Pathology of Hereditary Retinal Degeneration Associated with Hypobetalipoproteinemia

Background: The clinical features and previously unreported ocular pathology in a case of heterozygous hypobetalipoproteinemia (HBL) associated with a pigment epitheliopathy are documented. Night blindness developed in a white woman with familial heterozygous HBL (cholesterol and low-density lipoprotein levels < 5% of normal) at 51 years of age. Ophthalmoscopy showed bilateral symmetric depigmentation at the posterior pole with pigment clumping and pavingstone configuration in the periphery. By the time the patient died, at 75 years of age, vision had deteriorated to hand motions. Methods: One eye was removed 2 hours postmortem for light and electron microscopic study. Results: The photoreceptors were absent, and the outer nuclear layer was replaced by glial cells throughout most of the retina, but there was some focal photoreceptor preservation in isolated regions. The outstanding feature was a massive deposition of basal linear deposit which was calcified in segments and which contained macrophages and the processes of glial cells: trilaminar bodies and melanin granules were identified in the macrophages. The remaining retinal pigment epithelial cells contained melanin but very little lipofuscin: intraretinal migration was minimal. Conclusion: The authors postulate that the pigment epitheliopathy associated with HBL is an abiotrophy in which photoreceptor discs are unable to regenerate due to locally disordered metabolism resulting from or acting in concert with the pigment epitheliopathy.