Phenotype in retinol deficiency due to a hereditary defect in retinol binding protein synthesis

PURPOSE. To describe the phenotype caused by a retinol deficiency in a fami ly with compound heterozygous missense mutations (Ile41Asn and Gly75Asp) in the gene for serum retinol binding protein (RBP). METHODS. The two affected sisters, 17 (BR) and 13 (MR) years old, were exam ined clinically and with perimetry, color vision tests, dark adaptometry, r od- and cone-isolated; electroretinograms (ERGs), multifocal ERGs, electroo culograms (EOGs), and laboratory tests. RESULTS. There were no complaints besides night vision problems and no hist ory of systemic disease. Visual acuity was reduced to 20/40 (BR) and 20/25 (MR). Anterior segments were normal except for a discrete iris coloboma. Bo th patients showed a typical "fundus xerophthalmicus," featuring a progress ed atrophy of the retinal pigment epithelium. Dark adaptation thresholds we re elevated. In the scotopic ERG, only reduced mixed responses were recorda ble. The photopic ERG was reduced in BR and normal in MR; implicit times we re highly (BR) to slightly (MR) elevated. There was no (BR) to little (MR) light reaction in the EGG. All-trans retinol levels were 0.19 mu M and 0.18 mu M (normal range, 0.7-1.5 mu M) for BR and MR, respectively, and did not increase in a dose-response test. RBP was below detection threshold, and r etinyl eaters were normal. CONCLUSIONS. Both affected siblings had no detectable serum RBP, one sixth of normal retinol levers, and normal retinyl eaters. The retinal pigment ep ithelium was severely affected, but besides acne there were no changes to o ther organs. This gives evidence for an alternative tissue source of vitami n A, presumably retinyl esters from chylomicron remnants. The normal retino l levels in the tear fluid explain the lack of xerophthalmia. However, cons idering the role of RBP in the tear fluid and, during development, in the y olk sac there is also evidence that there are organ-specific RBP forms not affected by the genetic defect.