Retinal degeneration in abetalipoproteinemia

Abstract

Purpose : Genetic defects in MTTP are responsible for abetalipoproteinemia, combining spinocerebellar and retinal degeneration. Retinal findings in abetalipoproteinemia are only infrequently reported. We provide a detailed phenotypic description of the retinal degeneration linked with MTTP variants in a cohort of retinitis pigmentosa (RP) patients.

Methods : Patients previously diagnosed with abetalipoproteinemia and patients with gene defects in MTTP identified through next generation sequencing were investigated at the national reference center for rare ocular diseases of Quinze-Vingts hospital. Best corrected visual acuity (BCVA), slit-lamp examination, Goldman perimetry, full field electroretinography (ffERG) and multimodal imaging including color photos, short (SWAF) and near infrared wavelength autofluorescence, optical coherence tomography (OCT) were done for all patients.

Results : Four female patients from four unrelated families were selected. Median BCVA at baseline was 20/40 (range: 20/25 – 20/250). ffERG showed cone-dominated responses. Isopter V4e of Goldman visual field was constricted in all patients. Three patients had fundus findings typical of RP. Two had atrophic patches at the posterior pole. One had angioid streaks and “peau d'orange” aspect. SWAF showed various features. One patient had a ring of increased autofluorescence; another had a water-shed hyperautofluorescent line beneath the macula. One individual had numerous hyperautofluorescent dots scattered over the posterior pole. One patient had confluent hypoautofluorescent patches with scalloped edges.OCT showed a destruction of outer retinal layers outside the macula in all patients. In one individual OCT discovered a type 2 subretinal neovascularization.Two patients had prominent ataxia and peripheral sensitive-motor neuropathy. One patient developed a parietal hemorrhage related with low vitamin K plasmatic level. One patient developed an acute myeloid leukemia. Two patients are free of neurological symptoms to date. All patients descended from inbreed pedigrees. Three individuals harbored known homozygous variants in MTTP. Genetic data were lacking for one patient.

Conclusions : Abetalipoproteinemia represents 0.2% of our RP cohort. Retinal degeneration in abetalipoproteinemia can take various and atypical aspects. It could be the first clinical sign of the disease. On the basis of these findings, we strongly recommend adding MTTP to inherited retinal degeneration gene panels.

This is a 2021 ARVO Annual Meeting abstract.