Slow progressive very late-onset LAL-D: the importance of liver biopsy

Question/Clinical Case:

A 68-year old woman presented to our center for further evaluation of elevated liver function tests. She reported a 20 years history of elevated liver enzymes. Histology results similarly demonstrated microvesicular fatty liver with minimal fibrosis. Re-examination of a biopsy taken in 2008 did already show foamy macrophages which had been overlooked at that time. In line with the patient's metabolic profile, her case was treated as NASH-related although histological criteria were not fulfilled completely.

Methods:

After referral to our center, we performed enzymatic dry blood spot (DBS) test which showed reduced Liposomal Acid Lipase (LAL) activity. Another liver biopsy was taken which now showed fibrosis stage III, a mixed pattern of steatosis as well as discernible macrophages transformed into foamy cells. In addition, we had the unique opportunity to perform electron microscope (EM) examination, which is a rare possibility for this disease.

Results:

EM pictures revealed pathognomonic membrane-bound lipid drops within the lysosome of hepatocytes clearly proving the diagnosis of LAL-D. Subsequently, treatment with Sebelipase alpha was initiated.

Conclusions:

Usually, the median age of first reported manifestation of LAL-D is around 5 years and 83% of cases manifested by an age of 12. However, disproportionately younger age of LAL-D patients compared with the general population suggests that many LAL-D patients may be missed; possibly even die prior to diagnosis. Our patient had a slowly progressive form although no enzyme activity was detected. Indeed, it took her more than 20 years to progress from stage I to III fibrosis. This slow progression is actually a hallmark in NAFLD.