Severe hypertriglyceridemia secondary to splice-site and missense variants in LMF1 in three patients from Ecuador

Garay-García, Karla; Gaete, Paula V.; Mendivil, Carlos O.

doi:10.1016/j.jacl.2022.02.006

Cited by 4 publications

(2 citation statements)

References 17 publications

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“…The ALT levels remain stable over a wide range of triglyceride concentrations–in particular, in a biologically relevant range of up to ~1000 mg/dL triglycerides ( Figure 5 A) despite increasing turbidity with increasing triglyceride concentrations in the samples. The only significantly different triglyceride level compared with 0 mg/dL is 10,000 mg/dL with significantly higher ALT levels; however, this triglyceride concentration is very unlikely to be present in rodents or humans outside of rare familial syndromes [ 24 ]. The high NADH ALT reagent shows high precision across a wide triglyceride range of 0–10,000 mg/dL with a CV of 10.35 for ALT standard 31.25 ( n = 8 for all standards, see Supplemental Material S1 for raw data), CV of 4.35 for ALT standard 62.5, CV of 4.62 for ALT standard 125, and CV of 2.04 for ALT standard 250; and across a wide biological more relevant triglyceride range 0–500 mg/dL with a CV of 0.92 for ALT standard 31.25, CV of 1.70 for ALT standard 62.5, CV of 1.24 for ALT standard 125, and CV of 1.51 for ALT standard 250.…”

Section: Expected Results and Discussionmentioning

confidence: 99%

Inexpensive, Accurate, and Stable Method to Quantitate Blood Alanine Aminotransferase (ALT) Levels

Hartmann

Schnabl

2022

MPs

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Alanine aminotransferase (ALT) levels are frequently determined in serum and plasma samples and are a primary measure to quantitate hepatocellular injury in rodents, humans, and other organisms. An accurate, reliable, and scalable assay is hence of central importance. Here, we describe a methodology that fulfills those requirements, and demonstrates an excellent performance similar to a commercial ALT kit, with a long stable performance over several subsequent runs. Further, anticoagulation of blood samples with ethylenediaminetetraacetic acid (EDTA) or heparin results in similar ALT concentrations with this assay, whereas no anticoagulation significantly increases ALT levels. Mild hemolysis does not significantly increase ALT levels; however, moderate to severe hemolysis does lead to higher ALT levels. The assay provides stable results over a wide range of associated triglyceride concentrations that can be expected in serum and plasma samples from rodents and humans with dyslipidemia. It also performs well in diluted samples with a reduction of ALT levels corresponding to the factor used to dilute the samples. The described ALT reagent is also very affordable, costing less than 1/80 of comparable commercial kits. Based on the characteristics above, this methodology is suitable for a broad spectrum of applications in mice and possibly humans, where ALT concentrations need to be determined.

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Section: Expected Results and Discussionmentioning

confidence: 99%

Inexpensive, Accurate, and Stable Method to Quantitate Blood Alanine Aminotransferase (ALT) Levels

Hartmann

Schnabl

2022

MPs

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“…More than 200 mutations have been documented within the 30 kb LPL gene, which consists of 10 exons and encodes a protein of 475 amino acids with a 27 amino acid signal peptide, with only a limited number having been evaluated for pathogenesis [ 122 ]. A study conducted in Oman in a consanguine population revealed an association between F-HTG and alteration in multiple genes, which included LPL as well as APOC2, APOA5, GPIHPB1, and LMF1, implying that the genetic disorder is polygenic [ 123 ]; this finding has been supported by evidence from China, which indicates that the severity of F-HTG is digenic [ 124 ] and is likely to involve several molecular mechanisms, including splice-site variation [ 125 ]. The treatment of F-HTG focuses on the reduction of low-density lipoprotein (LDL) cholesterol levels, followed by management of non–high-density lipoprotein cholesterol levels; this can be achieved by changes in lifestyle and dietary modifications [ 126 ] or by the administration of statins such as Atorvastatin, Lovastatin, Fluvastatin, Pravastatin Rosuvastatin and Simvastatin [ 127 ].…”

Section: Familial Hypertriglyceridemiamentioning

confidence: 99%

Current Understanding on the Genetic Basis of Key Metabolic Disorders: A Review

Rodrigues

Yong

Bhuiyan

et al. 2022

Biology

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Advances in data acquisition via high resolution genomic, transcriptomic, proteomic and metabolomic platforms have driven the discovery of the underlying factors associated with metabolic disorders (MD) and led to interventions that target the underlying genetic causes as well as lifestyle changes and dietary regulation. The review focuses on fourteen of the most widely studied inherited MD, which are familial hypercholesterolemia, Gaucher disease, Hunter syndrome, Krabbe disease, Maple syrup urine disease, Metachromatic leukodystrophy, Mitochondrial encephalopathy lactic acidosis stroke-like episodes (MELAS), Niemann-Pick disease, Phenylketonuria (PKU), Porphyria, Tay-Sachs disease, Wilson’s disease, Familial hypertriglyceridemia (F-HTG) and Galactosemia based on genome wide association studies, epigenetic factors, transcript regulation, post-translational genetic modifications and biomarker discovery through metabolomic studies. We will delve into the current approaches being undertaken to analyze metadata using bioinformatic approaches and the emerging interventions using genome editing platforms as applied to animal models.

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Genetic variants in triglyceride metabolism genes among individuals with hypertriglyceridemia in Colombia

Puerto-Baracaldo,

Amaya-Montoya,

Parra-Serrano

et al. 2024

Journal of Clinical Lipidology

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Severe hypertriglyceridemia secondary to splice-site and missense variants in LMF1 in three patients from Ecuador

Cited by 4 publications

References 17 publications

Inexpensive, Accurate, and Stable Method to Quantitate Blood Alanine Aminotransferase (ALT) Levels

Inexpensive, Accurate, and Stable Method to Quantitate Blood Alanine Aminotransferase (ALT) Levels

Current Understanding on the Genetic Basis of Key Metabolic Disorders: A Review

Genetic variants in triglyceride metabolism genes among individuals with hypertriglyceridemia in Colombia

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