LAL-D, the rare condition that lies hidden between fatty liver and high cholesterol
Lysosomal acid lipase deficiency is a progressive genetic metabolic disorder that often goes undiagnosed for years: new treatment eligible for reimbursement
Key points
Persistent abnormalities in cholesterol levels, an enlarged liver, elevated transaminases, or a diagnosis of fatty liver disease that does not fully explain the clinical picture. Behind seemingly common symptoms, a rare disease may sometimes lie hidden: lysosomal acid lipase deficiency (LAL-D), an ultra-rare and progressive genetic metabolic disorder that often goes unrecognised for years. Meanwhile, damage to the liver and metabolism continues to progress silently, increasing the risk of hepatic and cardiovascular complications. This challenge is now even more significant thanks to the availability in Italia of a specific treatment recently approved for reimbursement by the Italian Medicines Agency (AIFA).
A metabolic disorder that can progressively damage the liver
LAL-D is caused by a deficiency or reduced activity of the enzyme lysosomal acid lipase (LAL), an enzyme that normally breaks down cholesterol and triglycerides within lysosomes, the cells’ ‘recycling centres’. When this mechanism does not function properly, lipids gradually accumulate, particularly in the liver, spleen and other tissues, causing metabolic abnormalities and organ damage.
In adults, the condition may present with a persistent rise in transaminases, an enlarged liver and hepatic steatosis. Over time, the accumulation of fat can promote inflammatory and fibrotic processes, leading to the development of cirrhosis and, in the most severe cases, liver failure. These manifestations are often associated with elevated levels of LDL cholesterol and triglycerides, and a reduction in HDL cholesterol.
The challenge of diagnosis: a rare disease masked by common symptoms
LAL-D presents with a heterogeneous clinical picture, with symptoms that may overlap with those of more common conditions, such as familial hypercholesterolaemia or hepatic steatosis associated with metabolic dysfunction.
In adults, the absence of specific symptoms can contribute to further delays in diagnosis. Abnormalities in blood tests are sometimes attributed to other causes, leading patients to undergo years of diagnostic and therapeutic procedures without identifying the root cause of the problem. In many cases, the journey to a diagnosis can take years, during which liver damage continues to progress, often silently and progressively.
