Abstract
Purpose :
LCHADD is an early-onset autosomal recessive fatty acid metabolism disorder due to mutations in HADHA, the LCHAD Trifunctional Multienzyme Complex Alpha Subunit gene, associated with progressive vision loss. Due to high early mortality, previous studies focused mostly on very young patients. Herein, we characterized 4 LCHADD patients in the second to third decade.
Methods :
We retrospectively evaluated the records of 4 genetically and biochemically confirmed LCHADD patients (3M/1F; ages 13-21yo) with complete eye exams inclusive of ETDRS acuity, kinetic perimetry, full-field flash (ff)ERGs, multi-focal (mf)ERGs, electrooculograms (EOG), spectral domain (SD)-OCT, wide-field fundus autofluorescence (WF-FAF), fluorescein angiography, and color photography.
Results :
According to the classification proposed by Tyni et al. (1998), 1 case was stage 2 OU, 2 cases were stage 3 OU, and 1 case progressed from stage 3 to 4 in OD and stage 2 to 3 in OS over a 7-year period. Mean visual acuity was 20/60 (range 20/20 – 20/400). All cases had central/paracentral scotomas and progressive central choroidal and retinal pigment epithelium (RPE) atrophy. The widespread RPE atrophy presented as nummular, coalescent hypo-autofluorescent patches with peripheral sparing on WF-FAF. SD-OCTs showed ellipsoid zone (EZ) loss with outer retinal tubulations, subretinal hyperreflective material, ectatic lesions, RPE loss with marked hypertransmission defects, and severe choroidal thinning. Consistent with the widespread RPE disease, EOG Arden ratios ranged from borderline low (1.67) with severe light peak delays to markedly reduced (≤1.48). ffERGs ranged from normal to moderate reductions and delays in rod and cone responses, with disproportionately reduced a-waves and increased b/a-wave ratios, consistent with prevailing outer retinopathy. mfERGs showed either severe generalized or patchy response density depression, consistent with markedly reduced macular cone function.
Conclusions :
LCHADD exhibits choroideremia-like progressive features primarily affecting the RPE, choroid, and photoreceptors, beginning in the posterior pole with eventual foveal and progressive coloboma-like macular lesions and centrifugal involvement. Our report adds new mfERG and EOG data in a series of older patients, improving our understanding of the pathophysiology and characteristics of later-stage LCHADD.
This is a 2021 ARVO Annual Meeting abstract.