1 – Hospital Santo António dos Capuchos, Centro de Referência de Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Lisboa Central
2 - Serviço de Oftalmologia, Centro Hospitalar Universitário de Lisboa Norte
3 - CRI Oftalmologia Pediátrica, Centro Hospitalar Universitário de Lisboa Central
4 - Unidade de Doenças Metabólicas, Hospital Dona Estefânia, Centro de Referência de Doenças Hereditárias do Metabolismo, Centro Hospitalar Universitário de Lisboa Central
- Poster no 17th International Symposium of the Sociedade Portuguesa de Doenças Metabólicas, Fátima, 8 a 10 de setembro de 2021
Resumo:
INTRODUCTION: Fabry disease (FD) is an X-linked inherited disorder of glycosphingolipid metabolism due to deficient lysosomal α-galactosidase A activity, leading to progressive accumulation of globotriaosylceramide (GB3) in a variety of cell types. Heterozygous females may have an unpredictable phenotype, ranging from mild to severe cardio-cerebro-renal disease. We present a clinical case of an uncommon ophthalmological presentation in a young adult female with FD.
DESCRIPTION: Female patient diagnosed with FD at 21 years of age by family screening of p.S276N mutation in GLA gene, with reduced alpha-galactosidase A activity in leucocytes of 2.4 nmol/h/mg protein (reference range (RR) 36 – 80) and increased plasma lyso-Gb3 of 20 nmol/L (RR <1.3). At diagnosis, the only reported symptoms were mild acroparesthesia and fatigue. During organ involvement assessments, she presented with sudden right monocular visual loss. Ophthalmological examination and transcranial ultrasonography were compatible with central retinal artery occlusion (CRAO), confirmed by angiography. Further neuroimaging studies showed cerebral microangiopathy. Common cardiovascular risk factors (including drugs), autoimmune and thrombophilic disorders were excluded. Despite a normal echocardiogram, magnetic resonance T1 mapping suggested myocardial glycosphingolipid deposition. There was no evidence of renal or gastrointestinal involvement. This patient fulfilled clinical criteria to start treatment for FD, and due to an amenable mutation, she was proposed to initiate migalastat, in addition to antiplatelet aggregation.
DISCUSSION: As in other hereditary metabolic diseases, the eye is a susceptible organ for progressive deposition of glycosphingolipids in Fabry’s disease. Most consistent ocular manifestations include cornea verticillata, lens opacities and retinal or conjunctival vascular abnormalities. Ophthalmic emergencies with sudden vision loss, such as anterior ischemic optic neuropathy, ophthalmic artery occlusion, central retinal artery or vein occlusion, are rare but previously reported in small series, more commonly in patients under 30 years of age.
COMMENTS: Central retinal artery occlusion is a rare manifestation of FD. This case reports a heterozygous female with a classic phenotype of FD, who may benefit from early treatment, according to current European guidelines and recommendations.