Ophthalmic pathology in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency caused by the G1528C mutation

To define histopathologic features of a recently recognized chorioretinopathy associated with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency, a defect of mitochondrial fatty acid oxidation.Both eyes were obtained at autopsy from a child who died of LCHAD deficiency, caused by the G1528C mutation, at the age of 14 months. Routine histopathology and light microscopic immunohistochemistry were performed, with a panel of 12 antibodies to epithelial, mesenchymal, neuronal, and inflammatory cells, using the avidin-biotinylated peroxidase complex method.The cells of the retinal pigment epithelium (RPE) were rarefied, flattened, and hypopigmented in the posterior pole. The RPE cells reacted normally with MAb Vim 34B to vimentin, and MAb CAM 5.2 and CY-90 for cytokeratin 8 and 18. Scattered among them were many pigment-laden macrophages, reactive with MAb PG-M1. A thin outer nuclear layer in the macular region suggested loss of photoreceptor cells. In routine stainings, patent choriocapillary vessels were sparse. However, a collapsed network of capillaries could be identified by MAb QBEND-10 to the CD34 epitope of vascular endothelial cells. In the peripheral fundus, the RPE and choriocapillaris were normal.The ophthalmopathologic findings corresponded to clinically defined stage 2 of the chorioretinopathy of LCHAD deficiency. Histopathologically, this chorioretinopathy can be classified as diffuse choroidal atrophy with loss of the choriocapillaris. The findings suggest a primary fault at the level of the RPE and choriocapillaris and a secondary macrophage response.