Early prenatal diagnosis of lysosomal storage disorders by enzymatic and molecular analysis

Li, Duan; Lin, Yunting; Huang, Yi‐Zhi; Zhang, Wen; Jiang, Mao Fa; Li, Xiuzhen; Zhao, Xiaoyuan; Sheng, Huiying; Yin, Xi; Su, Xueying; Shao, Youxiang; Liu, Zongcai; Li, Dong-Zhi; Li, Fatao; Liao, Can; Liu, Li

doi:10.1002/pd.5329

Cited by 9 publications

(7 citation statements)

References 52 publications

(54 reference statements)

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“…According to clinical diversity, the diagnostic approach for these disorders is equally controversial and different diagnosis alternatives can be performed from neonatal screening to allow early therapeutic interventions, when these are available, as well as biomarkers identification. In this last point, significant advances have been done using mass spectrometry technology [94,95], as well as in the improvement of enzyme assays on different biological samples (urine, plasma, saliva, leukocytes, fibroblasts) or dry blood spots on filter paper, and molecular tests that in some cases allow to confirm the diagnostic [96,97].…”

Section: Figure 5 Sphingolipid Catabolism and Sphingolipidosismentioning

confidence: 99%

Sphingolipids and Cell Signaling: Relationship Between Health and Disease in the Central Nervous System

Af¹,

Da²,

Oy³

et al. 2021

Preprint

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Sphingolipids are lipids derived from an 18-carbons unsaturated amino alcohol, the sphingosine. Ceramide, sphingomyelins, sphingosine-1-phosphates, gangliosides and globosides, are part of this group of lipids that participate in important cellular roles such as structural part of plasmatic and organelle membranes maintaining their function and integrity, cell signaling response, cell growth, cell cycle, cell death, inflammation, cell migration and differentiation, autophagy, angiogenesis, immune system. The metabolism of these lipids involves a broad and complex network of reactions that convert one lipid into others through different specialized enzymes. Impairment of sphingolipids metabolism has been associated with several disorders, from several lysosomal storage diseases, known as sphingolipidoses, to polygenic diseases such as diabetes and Parkinson and Alzheimer diseases. Sphingolipids are mainly located in central nervous system, and their abundance and distribution depend on brain development state and cell type. Although several studies have expanded the knowledge about sphingolipids function both in health and disease, it is still necessary to continue their study to understand the cellular implications of novel sphingolipids. These studies will also contribute to the diagnosis and treatment of diseases in which these molecules are part of their pathophysiology. In this review, we summarize the main sphingolipid characteristics and current knowledge about the synthesis, catabolism, regulatory pathways, participation in action potential and ionic channels, among other relevant functions.

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Section: Figure 5 Sphingolipid Catabolism and Sphingolipidosismentioning

confidence: 99%

Sphingolipids and Cell Signaling: Relationship Between Health and Disease in the Central Nervous System

Af¹,

Da²,

Oy³

et al. 2021

Preprint

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“…Currently, molecular analyses using these three approaches have several roles in LD diagnosis: (1) to confirm the final diagnosis, mainly in milder and atypical cases [ 29 ]; (2) to clarify borderline biochemical results in screening and enzymatic assays, as obtained in carriers and pseudodeficiency cases (when enzyme activity is decreased but with no clinical consequences) [ 30 ]; (3) to characterize a novel gene associated with a new type of LD, such as the cases of VPS33A in MPSPS [ 21 ] and DESG1 in leukodystrophy [ 31 ]; (4) for prenatal diagnosis [ 32 , 33 ]; (5) to predict disease severity [ 34 , 35 ]; (6) for the identification of patients with variants amenable to targeted therapy [ 36 , 37 ].…”

Section: Molecular Diagnosis Advances For Lysosomal Diseasesmentioning

confidence: 99%

Precision Medicine for Lysosomal Disorders

et al. 2020

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Precision medicine (PM) is an emerging approach for disease treatment and prevention that accounts for the individual variability in the genes, environment, and lifestyle of each person. Lysosomal diseases (LDs) are a group of genetic metabolic disorders that include approximately 70 monogenic conditions caused by a defect in lysosomal function. LDs may result from primary lysosomal enzyme deficiencies or impairments in membrane-associated proteins, lysosomal enzyme activators, or modifiers that affect lysosomal function. LDs are heterogeneous disorders, and the phenotype of the affected individual depends on the type of substrate and where it accumulates, which may be impacted by the type of genetic change and residual enzymatic activity. LDs are individually rare, with a combined incidence of approximately 1:4000 individuals. Specific therapies are already available for several LDs, and many more are in development. Early identification may enable disease course prediction and a specific intervention, which is very important for clinical outcome. Driven by advances in omics technology, PM aims to provide the most appropriate management for each patient based on the disease susceptibility or treatment response predictions for specific subgroups. In this review, we focused on the emerging diagnostic technologies that may help to optimize the management of each LD patient and the therapeutic options available, as well as in clinical developments that enable customized approaches to be selected for each subject, according to the principles of PM.

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“…Thus, prenatal screening and prenatal diagnosis are important in this group of diseases. Different types of laboratory tests are used for determining these diseases such as enzyme analysis, mutation analysis, and various types of molecular techniques . In this study, we have evaluated the outcomes of prenatal enzymatic diagnosis of LSDs during the period from 1992 to 2018.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 They are mostly caused by complete or partial deficiency of lysosomal enzymes as a result of mutations in genes encoding for these enzymes. 3,4 The resultant progressive accumulation of undegraded substrates in the lysosomes and the endosomal-lysosomal system leads to cellular dysfunction and eventually cell death. The characteristic pathological feature of most LSDs is neurodegeneration.…”

Section: Introductionmentioning

confidence: 99%

“…Different types of laboratory tests are used for determining these diseases such as enzyme analysis, mutation analysis, and various types of molecular techniques. 4 In this study, we have evaluated the outcomes of prenatal enzymatic diagnosis of LSDs during the period from 1992 to 2018. The enzyme studies were carried out using chorionic villus sample (CVS) material, cultured amniotic cells, or fetal blood cells.…”

Section: Introductionmentioning

confidence: 99%

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Prenatal enzymatic diagnosis of lysosomal storage diseases using cultured amniotic cells, uncultured chorionic villus samples, and fetal blood cells: Hacettepe experience

et al. 2019

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Aim To evaluate the results of prenatal enzymatic diagnostic studies for detecting lysosomal storage diseases (LSDs) during 1992 to 2018. Methods Pregnancies subjected to “prenatal enzymatic diagnosis of LSDs” during 1992 to 2018 were retrospectively evaluated in terms of invasive prenatal tests, type of LSDs, and obstetric outcomes. Results A total of 142 pregnancies were evaluated for various types of LSDs of which 30, 103, and 9 cases were subjected to amniocentesis, chorionic villus sampling, and fetal blood sampling, respectively. Retrospective analysis of prenatal diagnosis revealed that LSDs affected 33% (47/142) of the fetuses. Sandhoff disease (28%), Tay‐Sachs disease (27%), and metachromatic leukodystrophy (MLD) (20%) were the most frequent LSDs among the evaluated cases with two false negatives, one each for Tay‐Sachs disease and MLD. Conclusion Enzymatic prenatal diagnoses of certain LSDs may serve as a primary intervention point for families with index cases of infantile or late infantile types of LSDs, since they are associated with poor outcomes, including mortality. In addition, enzyme studies alone may also be feasible for populations with increased risk of molecular heterogeneity, novel mutations, and low‐income settings where genetic analysis is inaccessible.

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Early prenatal diagnosis of lysosomal storage disorders by enzymatic and molecular analysis

Abstract: Based on different enzyme properties in uncultured CV, different prenatal diagnostic strategies should be adopted for MPS II and Pompe disease. Combining enzyme assay and molecular studies in uncultured CV improves the reliability of prenatal diagnosis of LSDs.

Cited by 9 publications

References 52 publications

Sphingolipids and Cell Signaling: Relationship Between Health and Disease in the Central Nervous System

Sphingolipids and Cell Signaling: Relationship Between Health and Disease in the Central Nervous System

Precision Medicine for Lysosomal Disorders

Prenatal enzymatic diagnosis of lysosomal storage diseases using cultured amniotic cells, uncultured chorionic villus samples, and fetal blood cells: Hacettepe experience

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