Lysosomal acid lipase deficiency in pediatric patients: a scoping review

Abstract Objective: Lysosomal acid lipase deficiency (LAL-D) is an underdiagnosed autosomal recessive disease with onset between the first years of life and adulthood. Early diagnosis is crucial for effective therapy and long-term survival. The objective of this article is to recognize warning signs among the clinical and laboratory characteristics of LAL-D in pediatric patients through a scope review. Sources: Electronic searches in the Embase, PubMed, Livivo, LILACS, Web of Science, Scopus, Google Scholar, Open Gray, and ProQuest Dissertations and Theses databases. The dataset included observational studies with clinical and laboratory characteristics of infants, children and adolescents diagnosed with lysosomal acid lipase deficiency by enzyme activity testing or analysis of mutations in the lysosomal acid lipase gene (LIPA). The reference selection process was performed in two stages. The references were selected by two authors, and the data were extracted in June 2020. Summary of the findings: The initial search returned 1593 studies, and the final selection included 108 studies from 30 countries encompassing 206 patients, including individuals with Wolman disease and cholesteryl ester storage disease (CESD). The most prevalent manifestations in both spectra of the disease were hepatomegaly, splenomegaly, anemia, dyslipidemia, and elevated transaminases. Conclusions: Vomiting, diarrhea, jaundice, and splenomegaly may be correlated, and may serve as a starting point for investigating LAL-D. Familial lymphohistiocytosis should be part of the differential diagnosis with LAL-D, and all patients undergoing upper gastrointestinal endoscopy should be submitted to intestinal biopsy.

mRNA transcription and protein expression of PPARgamma, FAS, and HSL in different parts of the carcass between fat-tailed and thin-tailed sheep

Background The objective of this study was to compare the level differences of mRNA transcription and protein expression of PPARγ, FAS and HSL in different parts of the carcass in different tail-type sheep. Six Tan sheep and six Shaanbei fine-wool sheep aged 9 months were slaughtered and samples were collected from the tail adipose, subcutaneous adipose, and longissimus dorsi muscle. The levels of mRNA transcription and protein expression of the target genes in these tissues were determined by real-time quantitative PCR and western blot analyses. Results The results showed that PPARγ, FAS, and HSL were expressed with spatial differences in tail adipose, subcutaneous adipose and longissimus dorsi muscle of Tan sheep and Shaanbei fine-wool sheep. Differences were also observed between the two breeds. The mRNA transcription levels of these genes were somewhat consistent with their protein expression levels. Conclusion The present results indicated that PPARγ, FAS and HSL are correlated with fat deposition, especially for the regulating of adipose deposition in intramuscular fat, and that the mRNA expression patterns are similar to the protein expression patterns. The mechanism requires clarification in further studies.

PPARgamma FAS, HSL mRNA and protein expression during Tan sheep fat-tail development

Background The objective of this study was to investigate proliferator-activated receptor (PPARγ), fatty acid synthase (FAS) and hormone-sensitive lipase (HSL) mRNA and protein expression in fat tails of Tan sheep. Rams from different developmental stages (aged 3, 6, 9, 12, 15 and 18 months) were selected, and their tail measurements including length (L), width (W) and girth (G) were recorded. The mRNA and protein expressions of PPARγ, FAS and HSL were examined by quantitative real-time polymerase chain reaction (PCR) and Western blot. Results The tail measurements increased with age. We observed no significant differences (P > 0.05) of PPARγ mRNA expression between ages 9 and 15 months, and between 12 and 15 months; FAS mRNA expression levels at each developmental stage were observed significantly in Tan sheep (P < 0.05); HSL mRNA expression with no significant differences were only observed between 6 and 15 months (P > 0.05). Significant differences (P < 0.05) of PPARγ, FAS and HSL protein expressions at each developmental stage were observed in Tan sheep. Conclusion We observed that the mRNA expression patterns of PPARγ and FAS decreased first before they increased again and then this process repeated. Conversely, the mRNA expression patterns of HSL increased first before they decreased and then this process repeated. The protein expression patterns of PPARγ and FAS decreased first before they increased again and then this process repeated. Conversely, the protein expression pattern of HSL increased first before it decreased again and then increased again.