Something fishy?

A 30-year-old man was admitted to our hospital for evaluation of lung nodules detected during pre transplant evaluation for his stage V chronic kidney disease (CKD). Sounds routine, but what caught me completely clueless was when I was told that he had CKD due to lecithin:cholesterol acyltransferase (LCAT) deficiency. A prominent physical finding on meeting him was the presence of bilateral peripheral corneal opacities at such a young age. On questioning, the patient reported that he was diagnosed with this condition on family screening after his father died following massive myocardial infarction due to dyslipidemia at the age of 35. A nice case report from KI can be found here or from NDT here.

Familial LCAT deficiency is a rare but possibly under diagnosed autosomal recessive disorder reported in families of European ancestry and is characterized by

1. Dyslipidemia – extremely low HDL levels (less than 10 mg/dL), increased cholesterol: cholesterol ester ratio with elevated triglycerides and total cholesterol.
2. Presence of corneal opacities giving the fish eye appearance.
3. CKD with proteinuria by 3rd-4th decade. Biopsy findings typically include - mesangial matrix expansion and foamy appearance of the glomerular basement membrane (GBM) on light microscopy, lipid droplets in the mesangial matrix, GBM and podocytes on electron microscopy with foot process effacement and segmental or global sclerosis eventually.
4. Mild hemolytic anemia.

Briefly, LCAT is an enzyme synthesized in the liver and primarily bound to HDL. It plays a prominent role in esterifying the cholesterol in the HDL thereby creating a concentration gradient for the cholesterol to move out of tissues thus helping HDL to function in reverse cholesterol transport (from tissues to liver). In patients with the LCAT deficiency, HDL-C maturation does not occur as unesterified cholesterol remains within the tissues and an abnormal lipoprotein called lipoprotein X (unesterified cholesterol and lecithin) is formed in the blood from the surface of chylomicron remnants not metabolized due to this enzyme deficiency. These lipid accumulations within the tissues explain the classic findings in these patients.

Although the mechanism of kidney injury is unknown, it is believed to be likely due to direct injury to the glomerular filtration barrier from the lipid deposition and/or inflammatory response due to lipoprotein X mediated monocyte recruitment and eventual glomerulosclerosis.

In our patient the diagnosis of LCAT deficiency was made by measuring the plasma assays for LCAT at the age of 6yrs. He had albuminuria by the age of 16 yrs but was lost to follow up and later presented with chronic kidney disease and nephrotic range proteinuria. He subsequently underwent renal biopsy that showed the above classic histological findings. He now has stage V CKD and is later scheduled to undergo live unrelated kidney transplantation. Liver transplantation is also being considered to decrease his risk of recurrence following transplantation.

Although this case is unique and perhaps rare, it highlights the importance of family history and careful physical examination particularly in patients with unexplained nephrotic syndrome. Next time, in such situations look closely into the eyes, you may find something fishy.

Viresh Mohanlal, MD

Image Credit to Tara Lemana