OPHTHALMOLOGIC FINDINGS IN LONG-CHAIN 3-HYDROXYACYL-COA DEHYDROGENASE-DEFICIENCY CAUSED BY THE G1528C MUTATION - A NEW-TYPE OF HEREDITARY METABOLIC CHORIORETINOPATHY

Objective: The purpose of the study was to determine the nature and co urse of ophthalmic abnormalities in long-chain 3-hydroxyacyl-CoA dehyd rogenase (LCHAD) deficiency, a recently discovered disorder of mitocho ndrial fatty acid beta-oxidation. Study Design: The study design was a cohort (case senses). Participants: A retrospective review of the rec ords of 15 children who had died during their first 2 years was perfor med. Also performed were a longitudinal reanalysis and cross-sectional clinical examination of four long-term survivors aged 5 to 31 years. Main Outcome Measures: Visual acuity, refraction, visual fields, ophth almoscopy, fluorescein angiography, biometry, corneal topography, elec troretinography (ERG), visual-evoked potentials (VEPs), color vision, and dark adaptation were measured. Results: In seven children, ophthal moscopic findings were within normal limits at 3 days to 13 months of age (median, 4.8 months). In 11 children, a granular retinal pigment e pithelium (RPE), with or without pigment clumping in the macula, was s een at 4 months to 5 years of age (median, 9 months). Two long-term su rvivors, 16 and 31 years of age, eventually had circumscribed atrophy of the choroid, RPE, and retina, which coincided with a posterior stap hyloma type 1. They had progressive axial myopia starting at 6 and 12 years of age and later paracentral scotomas leading to poor central vi sion. They suffered from early difficulty with mesopic vision, glare, and a severe generalized color vision deficiency that started as a tri tanomaly. A third survivor was mildly myopic at 5 years of age. All fo ur surviving patients had visually insignificant, flake-like supranucl ear opacities in the lens. The ERG initially was normal but deteriorat ed during the first decade and later was unrecordable. The VEP respons es remained fairly normal. Initially, angiography showed no blockade o f the choroidal fluorescence because of the thin RPE. Filling of choro idal vessels was delayed, and the choriocapillaris and, later, larger choroidal vessels in the posterior pole became nonperfused. Conclusion s: In LCHAD deficiency, the fundus is normal at birth (stage 1). Soon, however, pigment dispersion occurs in the RPE (stage 2), followed by circumscribed chorioretinal atrophy, occlusion of choroidal vessels, a nd deterioration of central vision, often with relative sparing of the peripheral fundus (stage 3). Finally, posterior staphylomas and centr al scotomas may develop (stage 4). Developmental cataract, progressive myopia, and deterioration of visual fields and color vision are new f indings in LCHAD deficiency. The chorioretinopathy and abnormal ERG pr ecede the development of myopia and posterior staphyloma, which, in tu rn, coincide with the loss of macular vision. The authors postulate th at the RPE or choriocapillaris is primarily affected. Awareness of the characteristic ocular features is important because of an opportunity for dietary treatment, genetic counseling, and prenatal diagnosis.