Lysosomal acid lipase deficiency in all siblings of the same parents

Maciejko, James J.; Anne, Premchand; Raza, Saleem; Lyons, Hernando

doi:10.1016/j.jacl.2017.02.006

Cited by 5 publications

(7 citation statements)

References 28 publications

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“…At the end of the selection process, only 108 articles were retained. 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , …”

Section: Resultsunclassified

“…Most were published in Germany, 50 , 64 , 74 , 80 , 95 , 101 Italy 25 , 48 , 73 , 77 , 89 , 90 , 91 , 92 , 96 , 109 and the United States. 18 , 19 , 20 , 29 , 37 , 42 , 43 , 44 , 45 , 49 , 52 , 55 , 56 , 61 , 67 , 72 , 78 , 83 , 84 , 108 , 111 , 114 …”

Section: Resultsmentioning

confidence: 99%

“…Most patients were from Italy, 25 , 48 , 73 , 77 , 89 , 90 , 91 , 92 , 96 , 109 Poland 75 , 76 , 113 and the United States. 18 , 19 , 20 , 29 , 37 , 42 , 43 , 44 , 45 , 49 , 52 , 55 , 56 , 61 , 67 , 72 , 78 , 83 , 84 , 108 , 111 , 114 The patients in selected articles were grouped into two categories: infantile-onset LAL-D, or CESD. A total of 206 patients were included, 73 with infantile LAL-D presentation and 133 with CESD.…”

Section: Resultsmentioning

confidence: 99%

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Lysosomal acid lipase deficiency in pediatric patients: a scoping review

Witeck

Schmitz

Oliveira

et al. 2022

Jornal de Pediatria

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Section: Resultsunclassified

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Lysosomal acid lipase deficiency in pediatric patients: a scoping review

Witeck

Schmitz

Oliveira

et al. 2022

Jornal de Pediatria

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“…This resulted in 47 known pathogenic variants from the literature being chosen. Table S3 lists these variants, as well as variants that were identified at later points in time from literature sources (Jones et al, ; Kim et al, ; Sjouke et al, ), and variants that were not amenable to plasmid‐based transfection due to being splicing mutations (Maciejko et al, ; Ruiz‐Andrés et al, ). All novel missense, frameshift or nonsense variants identified in patients participating in Sebelipase Alfa clinical studies ARISE (NCT0757184) and CL06 (NCT02112994) were selected. This resulted in seven more variants to be assayed.…”

Section: Methodsmentioning

confidence: 99%

Section: Variant Selection For Functional Assaysmentioning

confidence: 99%

Large‐scale functionalLIPAvariant characterization to improve birth prevalence estimates of lysosomal acid lipase deficiency

et al. 2019

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Lysosomal acid lipase (LAL) deficiency is an autosomal recessive disorder caused by LIPA gene mutations that disrupt LAL activity. We performed in vitro functional testing of 149 LIPA variants to increase the understanding of the variant effects on LAL deficiency and to improve disease prevalence estimates. Chosen variants had been reported in literature or population databases. Functional testing was done by plasmid transient transfection and LAL activity assessment. We assembled a set of 165 published LAL deficient patient genotypes to evaluate this assay's effectiveness to recapitulate genotype/phenotype relationships. Rapidly progressive LAL deficient patients showed negligible enzymatic activity (<1%), whereas patients with childhood/adult LAL deficiency typically have 1–7% average activity. We benchmarked six in silico variant effect prediction algorithms with these functional data. PolyPhen‐2 was shown to have a superior area under the receiver operating curve performance. We used functional data along with Genome Aggregation Database (gnomAD) allele frequencies to estimate LAL deficiency birth prevalence, yielding a range of 3.45–5.97 cases per million births in European‐ancestry populations. The low estimate only considers functionally assayed variants in gnomAD. The high estimate computes allele frequencies for variants absent in gnomAD, and uses in silico scores for unassayed variants. Prevalence estimates are lower than previously published, underscoring LAL deficiency's rarity.

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Frequency of rs1051338 and rs116928232 Variants in Individuals from Northwest Mexico

Hernández‐Orozco,

Melendez‐Aranda,

Mendoza‐Ruvalcaba

et al. 2024

Clinical Laboratory Analysis

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BackgroundLIPA, situated on chromosome 10q23.2‐q23.3, encodes the enzyme lysosomal acid lipase (LAL) (EC 3.1.1.13). Genetic alterations in LIPA lead to lysosomal acid lipase deficiency (LALD), an inborn error causing lipid metabolism anomalies and impairing cholesterol and triacylglyceride degradation. Over 40 LIPA variants have been documented, yet this study focuses on just two. The rs1051338 variant (NM_000235:c.46A>C) affects the signal peptide in Exon 2, whereas rs116928232, located in Exon 8, alters the splice site (NM_000235:c.894G>A), impacting lysosomal acid lipase activity. Considering the diverse clinical manifestations of LALD and the rising hepatic steatosis prevalence in Mexican population, mainly due to diet, these variants were investigated within this demographic to uncover potential contributing factors. This study aimed to reveal the frequency of rs1051338 and rs116928232 among healthy mestizo individuals in Northwest Mexico, marking a significant genetic exploration in this demographic.MethodsThree hundred ten healthy mestizo individuals underwent PCR‐RFLP analysis for both variants, and Sanger sequencing was performed for variant rs116928232. Bioinformatic analysis was also performed to predict protein changes.ResultsAllele frequencies for rs1051338 (FA = 0.39, p value = 0.15) and rs116928232 (FA = 0.0016, p value = 0.49) aligned with reported data, while bioinformatic analysis allowed us to identify the protein alteration observed in both variants; finally, the variants showed no linkage between them (normalized D′ = 1.03, p value = 0.56).ConclusionsAllelic frequencies closely matched reported data, and protein structure analysis confirmed variant impacts on LAL enzyme function. Notably, this study marks the first analysis of rs1051338 and rs116928232 in a healthy Mexican mestizo population.

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Lysosomal acid lipase deficiency in all siblings of the same parents

Cited by 5 publications

References 28 publications

Lysosomal acid lipase deficiency in pediatric patients: a scoping review

Lysosomal acid lipase deficiency in pediatric patients: a scoping review

Large‐scale functionalLIPAvariant characterization to improve birth prevalence estimates of lysosomal acid lipase deficiency

Frequency of rs1051338 and rs116928232 Variants in Individuals from Northwest Mexico

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