Lysosomal Acid Lipase Deficiency: An Uncommon Masquerader

Abstract

Lysosomal acid lipase deficiency (LALD) is a rare genetic disorder. This disease is due to decreased activity of lysosomal acid lipase which results in accumulation of cholesterol esters in lysosomes. This leads to liver cell damage and ultimately hepatic fibrosis. Most LALD patients present with abnormal liver enzymes and hyperlipidemia (HLD). In addition, patients with LALD have microvesicular steatosis on liver biopsy. However, this disease's presentation is not unique. The patient is a 29 year old male presenting with HLD and elevated liver enzymes. His workup was only significant for an anti-nuclear antibody titer of 1:160. Viral hepatitis serologies, ceruloplasmin, alpha-1 antitrypsin and iron studies were all within normal limits. A liver biopsy revealed diffuse microvesicular and medium droplet steatosis without large droplet fat vacuoles. Trichrome and reticulin stains showed thin bridging fibrosis (see image 1). Non-alcoholic steatohepatitis (NASH) was the presumptive diagnosis. His liver enzymes remained persistently elevated even after significant lifestyle modification and his lysosomal acid lipase level was tested. His enzyme level was undetectable and he was started on enzyme replacement therapy with sebelipase alfa. This case describes a common presentation of a rare disease, LALD. Due to the low incidence and nonspecific laboratory presentation of this disease, LALD is often misdiagnosed. NASH is becoming increasingly prevalent and is commonly diagnosed in patients with HLD and abnormal liver enzymes. A liver biopsy in a patient with this presentation that shows microvesicular steatosis will point the differential towards NASH. In those with NASH, statins are a mainstay therapy, but there is little evidence that these medications have benefit in LALD. While statins improve LDL and cholesterol levels in those with LALD, there is usually continued progression of liver disease with worsening steatosis and fibrosis. Therefore LALD patients misdiagnosed with NASH will receive incomplete therapy. The enzyme replacement agent sebelipase alfa hydrolyzes cholesterol esters that build up to cause the liver damage associated with LALD. Clinical trials with this drug have shown statistically significant decreases in LDL and liver enzymes in those with LALD. Now that there are treatment strategies for LALD, keeping this disease in the differential in patients with elevated liver enzymes and HLD is vital to ensure a chance at proper treatment.2325 Figure 1. Panel A: Medium drop-let macrovesicular steatosis and microvesicular steatosis Panel B: Acidophilic body Panel C: Kupffer cells with fat droplets Panel D: Bridging fibrosis