Oculocutaneous albinism type 4 E70.3

Oculocutaneous albinism type 4 is an autosomal recessive disorder of pigmentation of the skin, hair and eyes. The degree of hypopigmentation varies from mild to severe. Hair color ranges from white to yellow and blond to brown, with gray, blue-gray or brown irides. Nystagmus may be present. Other ocular anomalies include reduced visual acuity, macular hypoplasia, optic dysplasia or atypical choroidal vessels.

This is caused by mutatons in the SLC45A2 gene. The SLC45A2 gene encodes a putative transporter that is mainly expressed in pigment cells. The transporter protein is expressed at a late melanosome maturation stage where it functions as a proton/glucose exporter that increases lumenal pH by reducing glycolysis (Le L et al. 2020). SLC45A2 is ectopically expressed in HeLa cells and is localized in lysosomes. It increases lysosomal pH, suggesting that the expression of SLC45A2 in melanocytes, like the expression of OCA2, leads to a Ph shift in maturing melanosomes, which underpins melanin synthesis. The overexpression of OCA2 compensates for the loss of SLC45A2 expression during pigmentation. Experimental animal analyses of SLC45A2- and OCA2-deficient melanocytes show that SLC45A2 probably acts later during melanosome maturation than OCA2.

In a Japanese family of 16 patients, all showed depigmentation of the hair and/or iris. They had foveal hypoplasia, including 3 patients with grade 1 foveal hypoplasia, 7 with grade 2 and 6 with grade 3. Optical coherence tomography showed thinning of the macular ganglion cell complex in the temporal region and a slight impairment of visual field sensitivity in the centrotemporal region (Oki R et al. 2017).

1. Le L et al. (2020) SLC45A2 protein stability and regulation of melanosome pH determine melanocyte pigmentation. Mol Biol Cell 31:2687-2702.
2. Liu Y et al. (2022) Ablation of Proton/Glucose Exporter SLC45A2 Enhances Melanosomal Glycolysis to Inhibit Melanin Biosynthesis and Promote Melanoma Metastasis. J Invest Dermatol 142:2744-2755.
3. Oki R et al. (2017) A Japanese Family With Autosomal Dominant Oculocutaneous Albinism Type 4 Invest Ophthalmol Vis Sci 58:1008-1016