Lysosomal acid lipase deficiency in pediatric patients: a scoping review

Witeck, Camila da Rosa; Schmitz, Anne Calbusch; Oliveira, Júlia Meller Dias de; Porporatti, André Luís; Canto, Graziela De Luca; Pires, Maria Marlene de Souza

doi:10.1016/j.jped.2021.03.003

Cited by 11 publications

(8 citation statements)

References 127 publications

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“…Lipase 3 Substrate Specificity Differs From Human LIPA Human lysosomal acid lipase hydrolyzes TAG and CE (Witeck et al, 2021). Bacterially expressed Lip3 has been shown to have weak TAG lipase activity on short-chain fatty acid glyceryl trioctanoate but no detectable activity on glyceryl trioleate, a more physiological substrate (Alfaro-Chávez et al, 2019).…”

Section: Conditional Lipase 3 Gene Expression Control By Lipid Metabo...mentioning

confidence: 99%

“…Mutations in LIPA lead to lysosomal acid lipase deficiency, which can manifest as two clinical spectra: Wolman disease, which affects infants, and cholesteryl ester storage disease (CESD), which has a later onset. Both disease spectra are characterized by progressive accumulation of TAG and CE, leading to liver disease and early lethality ( Witeck et al, 2021 ). Expression of LIPA under nutrient restriction is regulated by Forkhead box protein O1 (FOXO1), the main downstream effector of insulin signalling, and by transcription factor EB (TFEB), a regulator of autophagy by promoting lysosome biogenesis ( Li and Zhang, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Drosophila Lipase 3 Mediates the Metabolic Response to Starvation and Aging

et al. 2022

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The human LIPA gene encodes for the enzyme lysosomal acid lipase, which hydrolyzes cholesteryl ester and triacylglycerol. Lysosomal acid lipase deficiency results in Wolman disease and cholesteryl ester storage disease. The Drosophila genome encodes for two LIPA orthologs, Magro and Lipase 3. Magro is a gut lipase that hydrolyzes triacylglycerides, while Lipase 3 lacks characterization based on mutant phenotypes. We found previously that Lipase 3 transcription is highly induced in mutants with defects in peroxisome biogenesis, but the conditions that allow a similar induction in wildtypic flies are not known. Here we show that Lipase 3 is drastically upregulated in starved larvae and starved female flies, as well as in aged male flies. We generated a lipase 3 mutant that shows sex-specific starvation resistance and a trend to lifespan extension. Using lipidomics, we demonstrate that Lipase 3 mutants accumulate phosphatidylinositol, but neither triacylglycerol nor diacylglycerol. Our study suggests that, in contrast to its mammalian homolog LIPA, Lipase 3 is a putative phospholipase that is upregulated under extreme conditions like prolonged nutrient deprivation and aging.

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Section: Conditional Lipase 3 Gene Expression Control By Lipid Metabo...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Drosophila Lipase 3 Mediates the Metabolic Response to Starvation and Aging

et al. 2022

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“…Тромбоцитопения присутствовала у 26% больных с инфантильной формой ДЛКЛ. Также при помощи лабораторного обследования было обнаружено повышение трансаминаз (33%), гиперхолестеринемия (8%), снижение холестерина ЛВП (37%), гипертриглицеридемия (22%), повышение уровня ферритина (16,4%) [7]. Кроме этого, отечественные авторы описывают наличие интермиттирующей лихорадки, симптомы угнетения центральной нервной системы на фоне развития печеночной недостаточности, повышение в крови С-реактивного белка и лактатдегидрогеназы [8][9][10].…”

Section: трудный диагнозunclassified

“…Известно о наличии признаков гемофагоцитоза в биоптатах костного мозга у больных с инфантильной формой ДЛКЛ [7]. Описаны случаи манифестации болезни Вольмана с развитием вторичного гемофагоцитарного синдрома [11].…”

Section: трудный диагнозunclassified

“…К ведущим клинико-лабораторным проявлениям БНЭХ относятся гепатомегалия (88%), спленомегалия (45%), повышение трансаминаз (68%), гиперхолестеринемия (78%), гипертриглицеридемия (53%), снижение холестерина ЛВП (50%). Диспептические явления встречаются реже, чем при БВ: отмечаются боли в животе (14%), вздутие живота (11%), диарея (8%) и рвота (5%) [7]. Неспецифичность клинических проявлений зачастую является причиной несвоевременной диагностики БНЭХ [14].…”

Section: трудный диагнозunclassified

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Lysosomal acid lipase deficiency – an underestimated cause of hypercholesterolemia in children

et al. 2022

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Lysosomal acid lipase deficiency (LAL-D) is a rare, progressive, autosomal recessive disease, which develops due to impaired degradation and subsequent intra-lysosomal accumulation of triglycerides and cholesterol esters causing dyslipidemia. The clinical manifestations of the disease presumably depend on the residual activity of the enzyme, lysosomal acid lipase. A profound deficiency of the enzyme known as Wolman’s disease has an onset in the first 6 months of life. The disease reveals itself by dyspeptic disorders in the form of vomiting and diarrhea, lack of weight gain, hepatosplenomegaly, and adrenal calcification. If the Wolman’s disease is not treated, children die within the first 6 months as a result of exhaustion caused by malabsorption syndrome combined with progressive deterioration of liver and adrenal glands. Partial deficiency of lysosomal acid lipase manifests itself at a later age and is called cholesterol ester storage disease. Its clinical presentations include hepatosplenomegaly, elevated transaminases, hypercholesterolemia, and, in some cases, hypertriglyceridemia. Liver failure is the main cause of death in the natural course of cholesterol ester storage disease. Delayed diagnosis of the disease leads to its progression causing irreversible liver damage. The implementation of mass screening programs with the determination of cholesterol levels in childhood is critical to identifying asymptomatic patients.The article presents a clinical case of a patient aged 3 years. The molecular genetic testing showed a mutation in exon 8 of the LIPA gene: NM_000235.3:c.894G>A synonymous variant in the homozygous state. It was also found that both parents of the girl had this type of mutation in the heterozygous state. The patient was prescribed sebelipase alfa in a dose of 1 mg/kg once every 14 days. The treatment was well tolerated. Due to the early verification of the diagnosis and timely pathogenetic therapy, the prognosis of the course of LAL-D, the duration and quality of life of the child were considered to be favourable.Raising the awareness of doctors along with the introduction of effective screening programs for the timely detection of dyslipidemia in children contributes to timely diagnosis and early initiation of pathogenetic therapy, which can increase the life expectancy of patients with lysosomal acid lipase deficiency and improve their quality of life.

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