Stargardt syndrome H35.5

Karl Stargardt, 1909

Familial-hereditary combination of oligophrenia, nephropathy, macular degeneration with bilateral central scotoma, light and color vision disorders. Stargardt syndrome is the most common form of macular degeneration in adolescence in which the center of the retina, the macula, is affected. It leads to progressive loss of central visual acuity: what you want to see clearly becomes blurred, distorted or disappears completely. The disease is hereditary and is caused by genetic mutations. These lead to the pigment epithelial cells surrounding the light-sensitive photoreceptors in the macula not breaking down their metabolic products. These accumulate, causing the tissue in the pigment epithelium and the photoreceptors to die.

A combination with aniridia or albinism (?) is rare.

Depending on the underlying mutation, the following types can be distinguished:

• STGD1 with mutations in the ABCA4 gene on chromosome 1 gene locus p22.1, autosomal recessive, by far the most common form. The ABCA4 protein is a retina-specific ABC transporter with N-retinylidene-PE as substrate. is expressed exclusively in photoreceptor cells of the retina. The gene product mediates the transport of an essential molecule, all-trans-retinal aldehyde (atRAL), across the photoreceptor cell membrane.
• STGD3 with mutations in the ELOVL4 gene on chromosome 6 at q14.1, autosomal dominant
• STGD4 with mutations in the PROM1 gene on chromosome 4 at p15.32, autosomal dominant

Under the influence of light, visual purple (11-cis-retinal) is converted into visual yellow (all-trans-retinal) in the photoreceptor cells, which is conjugated with phosphatidylethanolamine (PE) and transported out of the photoreceptor cells by a membrane ATPase (encoded by the ABCA4 gene). Mutations in the ABCA4 gene product lead to the accumulation of toxic degradation products of visual yellow in the photoreceptors, the most common cause of Stargardt syndrome.

1. Garces FA et al. (2020) Functional Characterization of ABCA4 Missense Variants Linked to Stargardt Macular Degeneration. Int J Mol Sci 22:185.
2. Quazi F et al. (2013) Differential phospholipid substrates and directional transport by ATP-binding cassette proteins ABCA1, ABCA7, and ABCA4 and disease-causing mutants. J Biol Chem 288: 34414-34426.