Familial LCAT Deficiency (FLD) is an ultra-rare autosomal recessive disorder caused by complete loss of function variants in the gene encoding for lecithin:cholesterol acyltransferase (LCAT).1FLD is characterized by very low HDL-Cholesterol (HDL-C) levels, often reduced LDL-Cholesterol (LDL-C) levels, elevated and variable triglycerides (TG), and the presence of abnormal lipoproteins such as lipoprotein X (LpX), which is believed to be nephrotoxic.1 Despite having significantly reduced HDL-C levels, FLD patients are not higher risk of atherosclerotic cardiovascular disease. 1,2 Common renal manifestations are proteinuria and chronic kidney disease (CKD) which leads to early end-stage renal disease (ESRD) usually by the 4th decade of life.1 Additionally, FLD patients exhibit hemolytic anemia and diffuse corneal opacity, which is commonly identified during childhood.1 The rate of renal function decline is highly variable in FLD patients, with some patients rapidly progressing to ESRD and others presenting with mild-moderate proteinuria for decades.1 The biomarkers of renal disease progression and potential risk factors for accelerated renal decline are poorly understood.

Here we describe a case in which renal function decline followed an unusual trajectory, characterized by a lag phase of normal function, followed by a rapid decline phase. With access to rich medical records data spanning more than three decades and an extensive clinical and biochemical characterization, we performed a quantitative comparative analysis of the changes in renal, hematologic, and lipid biomarkers with an unprecedented level of granularity. This case report suggests the identification of risk factors and early markers of disease progression to be used to optimize the clinical management of with existing therapies and aid the development of novel treatments.3