Lysosomal Acid Lipase Deficiency Leading to Liver Cirrhosis: a Case Report of a Rare Variant Mutation

Cunha‐Silva, Marlone; Mazo, Daniel F.; Corrêa, Bárbara; Lopes, Tirzah M.; Arrelaro, Raquel C.; Ferreira, Gabriel L.; Rabello, Marcello Imbrizi; Sevá‐Pereira, Tiago; Escanhoela, C.A.F.; Almeida, José R.

doi:10.5604/01.3001.0012.2125

Cited by 3 publications

(7 citation statements)

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“…However, one major limitation is that it is a single‐centre cross‐sectional study, and we, therefore, cannot establish a cause‐effect relationship between the reduction in LAL activity and the presence of liver damage. Thus, until new data become available, the reduction in LAL activity may be regarded to only as a marker of NAFLD severity . Furthermore, liver fibrosis was estimated by non‐invasive biomarkers, that despite being well validated, represent an indirect measure and do not provide neither a quantitative or qualitative evaluation of liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non‐alcoholic fatty liver disease

Baratta

Pastori

Tozzi

et al. 2019

Liver International

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Background and Aims Recent evidence showed a reduced activity of the lysosomal acid lipase (LAL) in patients with non‐alcoholic fatty liver disease (NAFLD) and cryptogenic cirrhosis (CC). However, the relationship between LAL activity and liver fibrosis has never been investigated. Methods Cross‐sectional study including 575 outpatients referred for the management of cardio‐metabolic and liver disease. The absence of liver fibrosis was defined by a FIB‐4 < 1.30 and NAFLD fibrosis score (NFS) <−1.455. LAL activity was measured with dried blood spot technique. Results Overall, 515 patients had a diagnosis of NAFLD (454 NAFL and 61 biopsy‐proven NASH) and 60 of CC. The value of LAL activity progressively decreased from healthy subjects to NAFL/NASH patients to CC (P < .001). LAL activity was reduced by 10% in patients with NAFL, by 20% in NASH and by 50% in CC. The prevalence of CC decreased across the tertiles of LAL activity: 22.2% in the lowest, 4.6% in the intermediate and 0.5% in the highest tertile. In NAFLD patients, 69.9% had a FIB4 < 1.30, and 43.1% a NFS <−1.455. Multivariate logistic regression analysis showed that Log (LAL activity) was associated with FIB‐4 < 1.30 (Odds ratio [OR] 2.19 95% confidence interval [CI] 1.33‐3.62, P = .002) and NFS < −1.455 (OR 2.43, 95% CI 1.51‐3.91, P < .001) after adjustment for confounding factors. Conclusions We found a progressive reduction of LAL activity according to liver disease severity. LAL activity was inversely associated with markers of liver fibrosis in patients with NAFLD.

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Section: Discussionmentioning

confidence: 99%

Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non‐alcoholic fatty liver disease

Baratta

Pastori

Tozzi

et al. 2019

Liver International

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“…LAL-D is underrecognized and some patients present with cirrhosis and signs of portal hypertension at diagnosis. [1,2] In affected adults, it is necessary to prevent and treat hepatic and cardiovascular complications, perform hepatocellular carcinoma (HCC) screening, and assess the need for liver transplantation. The specific approach consists of enzyme replacement (sebelipase alfa), which may improve the disease parameters such as transaminases, hepatomegaly, and dyslipidemia, reducing the progression of liver damage, [5][6][7] but this therapy is not widely available.…”

Section: Introductionmentioning

confidence: 99%

“…Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive genetic disorder associated with mutations in the gene LIPA, that encodes the enzyme lysosomal acid lipase (LAL). [1] Its clinical spectrum ranges from an earlier-onset presentation (Wolman´s disease), with high mortality in the first 2 years of life, to a later-onset form, known as cholesteryl esters storage disease (CESD), which is characterized by a systemic accumulation of cholesteryl esters and triglycerides, including in hepatocytes and Kupffer cells. Patients with CESD may have serum lipid abnormalities, hepatosplenomegaly, elevated liver enzymes and progress to atherosclerosis, chronic liver disease and complications.…”

Section: Introductionmentioning

confidence: 99%

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15-Year progression to liver cancer in the lack of treatment for lysosomal acid lipase deficiency: A case report

et al. 2022

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Rationale: Lysosomal acid lipase deficiency (LAL-D) is a poorly diagnosed genetic disorder characterized by the accumulation of cholesteryl esters and triglycerides in many tissues, leading to dyslipidemia and cardiovascular complications. In the liver, deposits are found within hepatocytes and Kupffer cells, generating microvesicular steatosis, progressive fibrosis, and cirrhosis. Sebelipase alfa is the target therapy which can improve laboratory changes and reduce the progression of liver damage, but this is not yet widely available.Patient Concerns: We are reporting a 15-year follow-up of a Brazilian man who was diagnosed with cirrhosis at age 43 and with LAL-D at age 53, but he has never been treated with sebelipase alfa for economic reasons. During the coronavirus disease 2019 (COVID-19) pandemic, he lost follow-up and missed three 6-month ultrasound exams for liver cancer screening.Diagnosis: At age 58, a remarkable deterioration in liver function was observed and he was diagnosed with hepatocellular carcinoma (HCC) outside the Milan Criteria (two nodules measuring 48mm and 25mm). Three other individuals with LAL-D and progression to liver cancer have been reported so far and none of them underwent enzyme replacement therapy: an 11-year-old girl with HCC, a 51-year-old male with cholangiocarcinoma, and a 21-year-old male with hepatocellular-cholangiocarcinoma. The latter had the same mutation in the gene LIPA as our patient, but a relationship between this variant and malignancies has not yet been established. Lessons:We emphasize how important is to treat LAL-D patients after diagnosis in order to avoid worsening liver function and progression to neoplasms. Untreated individuals should be considered at a higher risk but the most appropriate liver cancer screening program for this subgroup is still unknown.

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“…Lysosomal acid lipase deficiency (LAL-D), also named as cholesteryl ester storage disease and Wolman disease, is a multi-systemic autosomal recessive genetic disorder caused by mutations in the lysosomal acid lipase gene (LIPA) that encodes the enzyme lysosomal acid lipase (LAL). 1,2 LAL-D is responsible for the accumulation of triglycerides (TG) and progressive cholesteryl esters (CE) in most cells, including liver and spleen. 3 LAL-D is historically divided into two chief clinical phenotypes: earlyonset Wolman disease (WD) and late-onset cholesteryl ester storage disease (CESD).…”

mentioning

confidence: 99%

A rare cause of hepatomegaly and dyslipidemia: lysosomal acid lipase deficiency

Gürbüz¹,

Güney²,

Bulut³

et al. 2020

Turk J Pediatr

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Background. Lysosomal acid lipase deficiency (LAL-D), also known as cholesteryl ester storage disease or Wolman disease, is a multi-systemic autosomal recessive genetic disorder caused by mutations in the lysosomal acid lipase gene (LIPA). Case. A 14-year-old female patient was diagnosed as LAL-D with the findings of hepatomegaly, splenomegaly, elevated liver enzyme levels, and abnormal lipid profile. Her sister had similar laboratory and ultrasonographic findings. Both siblings had a homozygous c.894 G>A mutation in the LIPA gene, and their parents were heterozygous for this mutation. Conclusions. This case is one of the similar reports in the literature regarding clinical, biochemical, and genetic findings. It is well-known that LAL-D has overlapping clinical manifestations, and early diagnosis is quite challenging. Therefore, most patients die in the first year of life. After the determination of novel mutations in LAL-D patients, it is thought that LAL-D can present with heterogeneous signs and symptoms.

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Lysosomal Acid Lipase Deficiency Leading to Liver Cirrhosis: a Case Report of a Rare Variant Mutation

Cited by 3 publications

References 0 publications

Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non‐alcoholic fatty liver disease

Lysosomal acid lipase activity and liver fibrosis in the clinical continuum of non‐alcoholic fatty liver disease

15-Year progression to liver cancer in the lack of treatment for lysosomal acid lipase deficiency: A case report

A rare cause of hepatomegaly and dyslipidemia: lysosomal acid lipase deficiency

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