Crystalline Hepatopathy Associated With Bietti Crystalline Dystrophy: A Striking Manifestation of Disordered Fatty Acid Metabolism

Abstract

Bietti crystalline dystrophy (BCD) is a rare heritable retinal disease characterized by crystal deposition primarily in the retina. It is associated with atrophy of the retinal pigment epithelium (RPE) and is caused by variants in CYP4V2 , which encodes a cytochrome P450 hemethiolate protein superfamily member. CYP4V2 is involved in the selective hydrolysis of saturated medium chain fatty acids, and patients with BCD demonstrate abnormalities in fatty acid metabolism, including abnormal lipid profiles and the accumulation of the pathogenic crystals within the RPE, which leads to the visual pathologies characteristic of BCD. However, the precise identity of the crystals is currently unknown, and BCD has no established extraocular manifestations. Here, we report granulomatous hepatitis associated with abundant diffuse crystalline clefts in the hepatic parenchyma in 3 patients with retinal dystrophy and dyslipidemia: 2 with pathogenic CYP4V2 variants and 1 patient with clinical ophthalmologic findings suggestive of BCD but without available genetic testing. The unique and striking histologic features unifying the liver biopsies in all 3 patients strongly support a process related to abnormal fatty acid metabolism underlying the genetic disease of BCD, expanding the spectrum of BCD and shedding light on the importance of CYP4V2 in systemic fatty acid metabolism.