Current estimates suggest that about half of patients with long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiency, a type of long chain fatty acid oxidation disorder (LCFAOD), may suffer from retinopathy, with progressive chorioretinal atrophy and loss of visual acuity.

The mechanisms underlying the development of retinopathy in LCHAD deficiency are not well understood. Most likely, it has a multifactorial origin. For instance, it is hypothesized that long-chain 3-hydroxyacylcarnitines and/or related metabolites could be toxic for the retinal pigment epithelium (RPE) and/or photoreceptor cells. Moreover, metabolic decompensation and hospitalization seem to be associated with the progression of retinopathy.

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Retinitis pigmentosa is the most frequent ophthalmological manifestation observed in LCHAD patients, though others may occur. The identification of such manifestations in a proper timeframe is essential to provide patients with a better quality of life. In some cases, it is first detected by ophthalmologists, who should alert other pediatric specialties of the necessity of adopting a multidisciplinary approach to the case.

Early Diagnosis Could Improve Clinical Outcomes

A research team from the University Medical Center Hamburg-Eppendorf, Germany, found that early diagnosis of retinopathy in patients with LCHAD deficiency was associated with milder phenotype and better preservation of visual function. Their work was published in the journal Ophthalmic Genetics.

According to the researchers, the study “provides additional evidence of superior long-term visual outcome in LCHADD patients diagnosed by [population-wide newborn screening] and LCHADD patients with a nonprogressive history of grade 2 chorioretinopathy.”

Cell Model Created to Better Understand Vision Loss in Form of LCFAOD

The study enrolled 6 patients (average age, 14.9 years; range, 7.9–23.9 years) with retinal alterations. Among the patients diagnosed later in life, 2 presented with progressive atrophy and fibrosis of the choroidea, as well as RPE and photoreceptor degeneration. These alterations led to severe visual impairment despite adequate management. Another patient showed no signs of visual acuity declining during a 3-year follow-up.

The introduction of the NBS also had an important impact on the reduction of LCHAD deficiency-associated mortality and morbidity. “Patients diagnosed by NBS have shown to be less frequently affected by episodes of hypoglycemia, hypotonia/myopathy, hepatopathy, and cardiomyopathy as presumably sufficient energy supply is guaranteed as well as the reduction of long-chain acyl CoA esters and other toxic metabolites,” Dulz et al explained. This might also apply in the case of retinopathy.

The role of dietary optimization in LCHAD deficiency-associated chorioretinopathy is still controversial, nonetheless. For instance, supplementation with docosahexaenoic acid (DHA), but not a low-fat, high-carbohydrate diet, seems to help stabilize its progression.

Cones May Become Dysfunctional Prior to Rods

Researchers from France described the case of a 19-year-old female diagnosed with LCHAD deficiency who was subjected to ophthalmological assessments over a 17-year period. The assessment included visual acuity, visual field, ophthalmological assessments (OCT), flash electroretinograms (ERGs), pattern-electroretinograms (P-ERG), flash visual evoked potential (VEP) recordings, and electrooculogram (EOGs).

On the other hand, the 3 patients diagnosed by NBS retained good visual acuity over the entire follow-up period (average follow-up period, 6.2 years, range 2.8–9.6 years).

A Case of LCHAD Presenting as Retinitis Pigmentosa

The patient presented with decreased visual acuity, with progressive retinopathy and chorioretinopathy. Photophobia was noticed 2 years before registering a decrease in photopic-ERG amplitude. Decreased scotopic-ERG amplitude was only noticed 10 years after the initial decrease in photopic-ERG amplitude. Both EOGs and flash VEPs remained unaltered. Therefore, the researchers hypothesized that the dysfunction of the photopic system might occur before that of the scotopic system in patients with LCHAD deficiency.

“We know that cones have higher oxidative activity and energy needs than rods. The aerobic ATP demand of cones is greater in light-adapted [situations] than that of rods. In LCHAD-D [LCHAD deficiency], ATP generation by cones could be severely decreased modifying their visual cycle speed. Therefore, cone apoptosis would be accelerated in comparison with that of rods,” Rigaudière et al explained.

Choroidal Neovascularization Might Lead to Complications

Recently, Riccardo Sacconi, MD, FEBO, at the Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Italy, together with his colleagues Francesco Bandello, MD, FEBO, and Giuseppe Querques, MD, PhD, reported the case of a patient with LCHAD deficiency who developed choroidal neovascularization.

The patient, a 21-year-old female, presented with progressive visual decline in both eyes. In-depth ophthalmological studies revealed macular and midperipheral chorioretinal atrophy complicated by choroidal neovascularization in the left eye.

“We report for the first time the evidence that choroidal neovascularization could complicate ocular changes accelerating the progressive vision impairment,” the authors said. The case report was published in the journal Retinal Cases & Brief Reports.


Rigaudière F, Delouvrier E, Le Gargasson J-F, Milani P, Ogier de Baulny H, Schiff M. Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency and progressive retinopathy: one case report followed by ERGs, VEPs, EOG over a 17-year period. Doc Ophthalmol. 2021;142(3):371-380. doi:10.1007/s10633-020-09802-y

Dulz S, Atiskova Y, Engel P, Wildner J, Tsiakas K, Santer R. Retained visual function in a subset of patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD). Ophthalmic Genet. 2021;42(1):23-27. doi:10.1080/13816810.2020.1836658

Sacconi R, Bandello F, Querques G. Choroidal neovascularization associated with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Retin Cases Brief Rep. 2022;16(1):99-101. doi:10.1097/ICB.0000000000000923