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Biochim Biophys Acta Mol Cell Biol Lipids 2019 Apr 16. Epub 2019 Apr 16.

Department of Biology, Barnard College-Columbia University, New York, NY 10027, United States of America. Electronic address:

Niemann-Pick type C (NP-C) disease is a rare and fatal neurodegenerative disease typified by aberrations in intracellular lipid transport. Cholesterol and other lipids accumulate in the late endosome/lysosome of all diseased cells thereby causing neuronal and visceral atrophy. A cure for NP-C remains elusive despite the extensive molecular advances emanating from the identification of the primary genetic defect in 1997. Read More

J Clin Med 2019 Apr 17;8(4). Epub 2019 Apr 17.

Department of Public Medicine, University of Naples "Federico II", 80100 Naples, Italy.

Background: Fabry disease (FD) is a X-linked recessive lysosomal storage disorder characterized by altered biodegradation of glycosphingolipids. It is a multisystem pathology, also involving ophthalmological systems that show modifications of the vessel wall due to glycosphingolipid deposits. Optical coherence tomography angiography (OCT-A) allows for an objective analysis of retinal microvasculature alterations, evaluating retinal vessel density in macular region. Read More

Adv Healthc Mater 2019 Apr 18:e1801271. Epub 2019 Apr 18.

Center for Nanotechnology in Drug Delivery and Carolina Institute for Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

Extracellular vesicles (EVs) are promising natural nanocarriers for delivery of various types of therapeutics. Earlier engineered EV-based formulations for neurodegenerative diseases and cancer are reported. Herein, the use of macrophage-derived EVs for brain delivery of a soluble lysosomal enzyme tripeptidyl peptidase-1, TPP1, to treat a lysosomal storage disorder, Neuronal Ceroid Lipofuscinoses 2 (CLN2) or Batten disease, is investigated. Read More

ACS Med Chem Lett 2019 Apr 8;10(4):621-626. Epub 2019 Feb 8.

Department of Chemistry "Ugo Schiff", University of Firenze, via della Lastruccia n. 3-13, 50019 Sesto Fiorentino (FI), Italy.

Pharmacological chaperones (PCs) are small molecules that bind and stabilize enzymes. They can rescue the enzymatic activity of misfolded or deficient enzymes when they are used at subinhibitory concentration, thus with minimal side effects. Pharmacological Chaperone Therapy (PCT) is an emerging treatment for many lysosomal storage disorders (LSDs) including Gaucher disease, the most common, which is characterized by a deficiency in the GCase enzyme. Read More

Cell Physiol Biochem 2019 ;52(5):1139-1150

Department II of Internal Medicine and Center for Rare Diseases Cologne, University Hospital of Cologne, Cologne, Germany.

Background/aims: Fabry disease (FD) is a lysosomal storage disorder characterized by impaired alpha-galactosidase A (α-Gal A) enzyme activity due to mutations in the GLA gene. While virtually all tissues are affected, renal damage is particularly critical for the patients' outcome. Currently, powerful diagnostic tools and in vivo research models to study FD in the kidney are lacking, which is a major obstacle for further improvements in diagnosis and therapy. Read More

J Lipid Res 2019 Apr 15. Epub 2019 Apr 15.

University Bonn, Germany

The catabolism of ganglioside GM2 is dependent on three gene products. Mutations in any of these genes result in a different type of GM2 gangliosidosis (Tay-Sachs disease, B1 variant, Sandhoff disease and the AB-variant), with GM2 as major lysosomal storage compound. GM2 is also a secondary storage compound in lysosomal storage diseases like Niemann-Pick disease type A, B and C with primary storage of SM and cholesterol, respectively. Read More

Mol Genet Metab 2019 Apr 3. Epub 2019 Apr 3.

Department of Pediatric Metabolic Diseases, Emma Children's Hospital and Amsterdam Lysosome Center "Sphinx", Academic Medical Center, University Hospital of Amsterdam, Amsterdam, the Netherlands.

Background: Fabry disease is a rare, X-linked, lifelong progressive lysosomal storage disorder. Severely deficient α-galactosidase A activity in males is associated with the classic phenotype with early-onset, multisystem manifestations evolving to vital organ complications during adulthood. We assessed the ability of 2 low-dose agalsidase beta regimens to lower skin, plasma, and urine globotriaosylceramide (GL-3) levels, and influence clinical manifestations in male pediatric Fabry patients. Read More

Genet Mol Biol 2019 Apr 11. Epub 2019 Apr 11.

Postgraduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

Lysosomal storage disorders (LSDs) constitute a heterogeneous group of approximately 50 genetic disorders. LSDs diagnosis is challenging due to variability in phenotype penetrance, similar clinical manifestations, and a high allelic heterogeneity. A powerful tool for the diagnosis of the disease could reduce the "diagnostic odyssey" for affected families, leading to an appropriate genetic counseling and a better outcome for current therapies, since enzyme replacement therapies have been approved in Brazil for Gaucher, Fabry, and Pompe diseases, and are under development for Niemann-Pick Type B. Read More

Vet Pathol 2019 Apr 14:300985819839239. Epub 2019 Apr 14.

6 Total Veterinary Services, Christchurch, New Zealand.

A neurological disease was investigated in 3 German Shepherd pups from the same litter that failed to grow normally, appeared stiff, were reluctant to move, and were deaf. They developed intermittent seizures and ataxia and had proprioceptive defects. Histopathology showed severe vacuolation of neurons, astrocytes in nervous tissue, renal tubular epithelial cells, and macrophages in nervous tissue, spleen, and liver. Read More

Neurobiol Dis 2019 Apr 11;127:563-569. Epub 2019 Apr 11.

The Bateson Centre, University of Sheffield, Sheffield, UK; Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK. Electronic address:

Bi-allelic mutations in the glucocerebrosidase gene (GBA1) cause Gaucher's disease, the most common human lysosomal storage disease. We previously reported a marked increase in miR-155 transcript levels and early microglial activation in a zebrafish model of Gaucher's disease (gba1). miR-155 is a master regulator of inflammation and has been implicated in a wide range of different neurodegenerative disorders. Read More

Gene 2019 Apr 11;704:59-67. Epub 2019 Apr 11.

Department of Medical Genetics, Istanbul University, Medical School, Istanbul, Turkey.

Mucopolysaccharidosis IVA (MPS IVA) is a lysosomal storage disease caused by biallelic mutations in GALNS gene and characterized by progressive skeletal deformities with short stature. The aim of this study was to evaluate the genotype, longitudinal height measurement and clinical features of MPS IVA patients. Thirty-two patients from 22 families were enrolled. Read More

Mol Ther Methods Clin Dev 2019 Jun 2;13:321-333. Epub 2019 Mar 2.

Stem Cell and Neurotherapies, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.

Enzyme replacement therapy with laronidase is an established treatment for Mucopolysaccharidosis type I (MPS I), but its efficacy may be limited by the development of anti-drug antibodies, which inhibit cellular uptake of the enzyme. In a related disorder, infantile Pompe disease, immune tolerance induction with low-dose, short-course methotrexate appears to reduce antibody formation. We investigated a similar regimen using oral methotrexate in three MPS I patients. Read More

Pancreas 2019 04;48(4):459-470

Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles.

Acute pancreatitis (AP) is a potentially lethal inflammatory disease that lacks specific therapy. Damaged pancreatic acinar cells are believed to be the site of AP initiation. The primary function of these cells is the synthesis, storage, and export of digestive enzymes. Read More

Am J Transl Res 2019 15;11(3):1683-1696. Epub 2019 Mar 15.

Lysosomal and Rare Disorders Research and Treatment Center (LDRTC) Fairfax, VA 22030, USA.

Fabry disease (FD) is a rare X-linked genetic disorder caused by mutations in the gene encoding the lysosomal enzyme, α-galactosidase A (α-gal A). The mutations lead to lack of or faulty enzyme causing accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids including globotriaosylsphingosine (lyso-Gb). Treatment options for FD include enzyme replacement therapy. Read More

Acta Neurol Belg 2019 Apr 9. Epub 2019 Apr 9.

Department of Nephrology, University of Health Sciences Kartal Dr Lütfi Kırdar Training and Research Hospital, Istanbul, Turkey.

Fabry Disease (FD) is an X-linked lysosomal storage disease that emerges as a result of the mutations in the galactosidase A gene encoding alpha-galactosidase. The peripheral nervous system (PNS) involvement manifests itself as acroparesthetic complaints due to the small-fiber involvement. Our goal was to assess the PNS involvement of 14 patients with FD both clinically and electrophysiologically besides the other systemic features. Read More

J Pharm Sci 2019 Apr 5. Epub 2019 Apr 5.

Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia. Electronic address:

Mucopolysaccharidosis IVA (MPS IVA or Morquio A syndrome) is a lysosomal storage disease caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to lysosomal storage of keratan sulfate (KS) and chondroitin-6-sulfate. Currently, enzyme replacement therapy (ERT) using an enzyme produced in CHO cells represents the main treatment option for MPS IVA patients. As an alternative, we reported the production of an active GALNS enzyme produced in the yeast Pichia pastoris (prGALNS), which showed internalization by cultured cells through a potential receptor-mediated process and similar post-translational processing as human enzyme. Read More

Int J Neonatal Screen 2019 Mar 21;5(1). Epub 2018 Dec 21.

Head Reference Laboratory for Neonatal Screening, Center for Health Protection, National Institute for Public Health and the Environment (RIVM), P. O. Box 1, 3720 BA Bilthoven, The Netherlands.

All worldwide newborn screening (NBS) for lysosomal storage diseases (LSDs) is performed as a first-tier test by measurement of lysosomal enzymatic activities in dried blood spots (DBS). The currently two available methodologies used for measurement of enzymatic activities are tandem mass spectrometry (MS/MS) and digital microfluidics fluorimetry (DMF-F). In this chapter we summarize the workflows for the two platforms. Read More

Mol Genet Metab 2019 Mar 27. Epub 2019 Mar 27.

Mason Eye Institute, University of Missouri School of Medicine, Columbia, MO, USA. Electronic address:

The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage disorders characterized by progressive neurodegeneration and declines in neurological functions. Pathogenic sequence variants in at least 13 genes underlie different forms of NCL, almost all of which are recessively inherited. To date 13 sequence variants in 8 canine orthologs of human NCL genes have been found to occur in 11 dog breeds in which they result in progressive neurological disorders similar to human NCLs. Read More

J Clin Neurosci 2019 Apr 4. Epub 2019 Apr 4.

Department of Neurology, University of Arkansas for Medical Sciences, 4301 West Markham Street, Slot 500, Little Rock, AR 72205, United States.

Back Ground And Objective: Fabry's disease, is the most prevalent lysosomal storage disorder and is notorious for its early multi-organ involvement leading to complications, including ischemic strokes and transient ischemic attacks. Since 2001, enzyme replacement therapy (ERT) has become the mainstay treatment for Fabry's patients but the indications are not clearly defined. We did a meta-analysis of the available data to review the benefit of ERT for stroke prevention in Fabry's patients. Read More

Orphanet J Rare Dis 2019 Apr 3;14(1):78. Epub 2019 Apr 3.

Shandong University Qilu Hospital, No.107 Wen Hua Xi Road, Jinan, Shandong Province, China.

Background: Pompe disease is a rare, progressive, autosomal recessive lysosomal storage disorder caused by mutations in the acid α-glucosidase gene. This is the first report of Chinese patients from the global Pompe Registry. Chinese patients enrolled in the Registry ( ClinicalTrials. Read More

J Neurogenet 2019 Apr 2:1-6. Epub 2019 Apr 2.

a Department of Genetics , Hyogo College of Medicine , Nishinomiya , Japan.

The Drosophila spinster (spin) mutant was isolated as a mutant that showed abnormal morphology and function in the nervous system. The spin defect induces neural degeneration similar to human lysosomal storage diseases. Various studies have shown that Spin proteins are localized in lysosomes and participate in the late stages of the autophagic process. Read More

Mov Disord 2019 Apr 2. Epub 2019 Apr 2.

Parkinson's Disease and Movement Disorders Department, Hygeia Hospital, Athens, Greece.

Pharmaceuticals (Basel) 2019 Mar 29;12(2). Epub 2019 Mar 29.

Centro Singular de Investigación en Química Biolóxica e Materiais Moleculares, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain.

Here, the synthesis and glycosidase inhibition properties of the two first known 3-ethyloctahydro-1-indole-4,5,6-triols are reported. This study shows the transformation of d-glucose into polyhydroxylated 1-(2-nitrocyclohexane) acetaldehydes, followed by a protocol involving the formation of the azacyclopentane ring. Results of inhibitory potency assays and docking calculations show that at least one of them could be a lead for optimization in the search for compounds that behave like folding chaperones in lysosomal storage diseases. Read More

Stem Cell Res 2019 Mar 23;37:101427. Epub 2019 Mar 23.

National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Mucopolysaccharidosis type III B (MPS IIIB) is a lysosomal storage disorder caused by mutations in the NAGLU gene encoding N-acetylglucosaminidase. Here, we report the generation of a human induced pluripotent stem cell (iPSC) line from dermal fibroblasts of a MPS IIIB patient. The iPSC line has homozygous mutations of G>A transversion at nucleotide 457 of the NAGLU gene (457G>A), resulting in the substitution of lysine for glutamic acid at codon 153 (Glu153Lys). Read More

Neurobiol Dis 2019 Mar 28;127:362-373. Epub 2019 Mar 28.

Department of Neurological Sciences, Rush University Medical Center, Chicago, USA; Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, Chicago, USA. Electronic address:

The late-infantile Batten disease or late-infantile neuronal ceroid lipofuscinosis (LINCL) is an autosomal recessive lysosomal storage disorder caused by mutations in the Cln2 gene leading to deficiency of lysosomal enzyme tripeptidyl peptidase 1 (TPP1). At present, available options for this fatal disorder are enzyme replacement therapy and gene therapy, which are extensively invasive and expensive. Our study demonstrates that 3-hydroxy-(2,2)-dimethyl butyrate (HDMB), a brain endogenous molecule, is capable of stimulating TPP1 expression and activity in mouse primary astrocytes and a neuronal cell line. Read More

Kidney Int 2019 Mar 6. Epub 2019 Mar 6.

Department of Pediatrics, Division of Genetics, University of California, San Diego, La Jolla, California, USA. Electronic address:

Inflammation is involved in the pathogenesis of many disorders. However, the underlying mechanisms are often unknown. Here, we test whether cystinosin, the protein involved in cystinosis, is a critical regulator of galectin-3, a member of the β-galactosidase binding protein family, during inflammation. Read More

Mol Cell Proteomics 2019 Mar 29. Epub 2019 Mar 29.

Fondazione Pisana per la Scienza ONLUS, Italy

Krabbe disease is a rare, childhood lysosomal storage disorder caused by a deficiency of galactosylceramide beta-galactosidase (GALC). The major effect of GALC deficiency is the accumulation of psychosine in the nervous system and widespread degeneration of oligodendrocytes and Schwann cells, causing rapid demyelination. The molecular mechanisms of Krabbe disease are not yet fully elucidated and a definite cure is still missing. Read More

Sci Rep 2019 Mar 28;9(1):5292. Epub 2019 Mar 28.

Department of Physiological Chemistry, University of Veterinary Medicine Hannover, 30559, Hannover, Germany.

Niemann-Pick Type C (NP-C) is an inherited neurovisceral lysosomal storage disease characterized by a defect in the trafficking of endocytosed cholesterol. In 95% of patients the gene encoding NPC1 is affected. The correlation of the genetic background in NP-C with the clinical phenotype such as, severity and onset of liver dysfunction, ataxia, dystonia and vertical gaze palsy, has not been elucidated at the molecular level. Read More

EBioMedicine 2019 Mar 25. Epub 2019 Mar 25.

Department of Pediatrics, Erasmus University Medical Center, Rotterdam, Netherlands; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, Netherlands; Center for Lysosomal and Metabolic Diseases, Erasmus University Medical Center, 3015 GE Rotterdam, Netherlands. Electronic address:

Background: Neonatal screening for Pompe disease is complicated by difficulties in predicting symptom onset in patients with the common c.-32-13T>G (IVS1) variant/null (i.e. Read More

Am J Med Genet A 2019 Mar 28. Epub 2019 Mar 28.

Departments of Medicine and Physiology, Hôpital du Sacré-Coeur, University of Montreal, Montreal, Quebec, Canada.

Circ Genom Precis Med 2019 Mar;12(3):e002395

Department of Clinical Genetics (S.D., M.A. v. S, M.L., M.W.W., G.J.S.), Sophia Children's Hospital, Erasmus Medical Centre, Erasmus University, Rotterdam, the Netherlands.

Biochim Biophys Acta Mol Basis Dis 2019 Mar 21. Epub 2019 Mar 21.

Department of Gastroenterology, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile. Electronic address:

Lysosomes are dynamic organelles, which can fuse with a variety of targets and undergo constant regeneration. They can move along microtubules in a retrograde and anterograde fashion by using motor proteins, kinesin and dynein, being main players in extracellular secretion, intracellular components degradation and recycling. Moreover, lysosomes interact with other intracellular organelles to regulate their turnover, such as ER, mitochondria and peroxisomes. Read More

Mol Biol (Mosk) 2019 Jan-Feb;53(1):28-36

Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182 Russia.

Parkinson's disease (PD) characterized with slow continuous degeneration of dopaminergic neurons in the substantia nigra is one of the most common neurodegenerative diseases, but its etiology and pathogenesis are not fully understood. The pathogenesis of PD involves the impairment of lysosomal autophagy, which also contributes to lysosomal storage disorders (LSDs). In this work, the expression of genes related to lysosomal autophagy: Hspa8, Lamp2, Tfam, Slc18a2, and Vps35, was analyzed in the brain tissues of mice with the earliest stage of MPTP-induced PD. Read More

Traffic 2019 Mar 21. Epub 2019 Mar 21.

Department of Medical Biochemistry, Leiden Institute of Chemistry, Leiden University, RA, Leiden, the Netherlands.

β-Glucocerebrosidase (GBA) is the enzyme that degrades glucosylceramide in lysosomes. Defects in GBA that result in overall loss of enzymatic activity give rise to the lysosomal storage disorder Gaucher disease, which is characterized by the accumulation of glucosylceramide in tissue macrophages. Gaucher disease is currently treated by infusion of mannose receptor-targeted recombinant GBA. Read More

J Lipid Res 2019 Mar 20. Epub 2019 Mar 20.

Institute of Molecular Biosciences, University of Graz, Austria;

Bis(monoacylglycerol)phosphate (BMP) is a phospholipid crucial for lipid degradation and sorting in acidic organelles. Genetic and drug-induced lysosomal storage disorders (LSD) are associated with increased BMP concentrations in tissues and in the circulation. Data on BMP in disorders other than LSD, however, are scarce and key enzymes regulating BMP metabolism remain elusive. Read More

Proteomics 2019 Mar 19:e1800432. Epub 2019 Mar 19.

Department of Chemistry, University of Illinois at Chicago, Chicago, IL, 60607, USA.

Niemann-Pick disease, type C1 (NPC1) is a fatal, autosomal recessive, neurodegenerative disorder caused by mutations in the NPC1 gene. As a result, there is accumulation of unesterified cholesterol and sphingolipids in the late endosomal/lysosomal system. This abnormal accumulation results in a cascade of pathophysiological events including progressive, cerebellar neurodegeneration, among others. Read More

Expert Opin Drug Discov 2019 May 19;14(5):499-509. Epub 2019 Mar 19.

a Orphazyme A/S , Copenhagen , Denmark.

Introduction: Niemann-Pick type C (NPC) is a neurovisceral, progressively detrimental lysosomal storage disease with very limited therapeutic options and no approved treatment available in the US. Despite its rarity, NPC has seen increased drug developmental efforts over the past decade, culminating in the completion of two potential registration trials in 2018. Areas covered: This review highlights the many available animal models that have been developed in the field and briefly covers classical and new cell technologies. Read More

Cold Spring Harb Mol Case Stud 2019 Mar 18. Epub 2019 Mar 18.

Institute of Biomedicine, Sahlgrenska Academy, Gothenburg University.

Beta-mannosidosis is a lysosomal storage disorder characterized by accumulation of disaccharides due to deficiency of the lysosomal enzyme beta-mannosidase. The disease is caused by mutations in MANBA and is extremely rare in humans. Although the clinical presentation is heterogeneous, common symptoms include various degrees of developmental delay, behavioral disturbances, hearing loss and frequent infections. Read More

Hum Mutat 2019 Mar 18. Epub 2019 Mar 18.

Section Cell Biology of Rare Diseases, Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Mutations in the GNPTAB and GNPTG genes cause mucolipidosis (ML) type II, type III alpha/beta, and type III gamma, which are autosomal recessively inherited lysosomal storage disorders. GNPTAB and GNPTG encode the α/β-precursor and the γ-subunit of N-acetylglucosamine (GlcNAc)-1-phosphotransferase, respectively, the key enzyme for the generation of mannose 6-phosphate targeting signals on lysosomal enzymes. Defective GlcNAc-1-phosphotransferase results in missorting of lysosomal enzymes and accumulation of non-degradable macromolecules in lysosomes, strongly impairing cellular function. Read More

Int J Neonatal Screen 2018 Sep 9;4(3). Epub 2018 Jul 9.

Departments of Chemistry, University of Washington, Seattle, WA 98195, USA;

All of the worldwide newborn screening (NBS) for lysosomal storage diseases (LSDs) is done by measurement of lysosomal enzymatic activities in dried blood spots (DBS). Substrates used for these assays are discussed. While the positive predictive value (PPV) is the gold standard for evaluating medical tests, current PPVs for NBS of LSDs cannot be used as a performance metric due to statistical sampling errors and uncertainty in the onset of disease symptoms. Read More

EJIFCC 2019 Mar 1;30(1):82-87. Epub 2019 Mar 1.

Laboratory of Hematology, Mohammed VI University Hospital, Oujda, Morocco.

Gaucher disease (GD) is a lysosomal storage disease. It corresponds to a congenital deficit in β-glucocerebrosidase. This pathology should be considered in the presence of unexplained splenomegaly, with or without signs of haemorrhage, skeletal manifestations or hepatomegaly. Read More

Mol Ther 2019 Apr 6;27(4):878-889. Epub 2019 Mar 6.

Translate Bio, Lexington, MA 02141, USA. Electronic address:

Fabry disease is a lysosomal storage disorder caused by the deficiency of α-galactosidase A. Enzyme deficiency results in a progressive decline in renal and cardiac function, leading to cardiomyopathy and end-stage renal disease. Current treatments available, including enzyme replacement therapies, have provided significant benefit to patients; however, unmet medical needs remain. Read More

Am J Hum Genet 2019 Apr 14;104(4):625-637. Epub 2019 Mar 14.

Moderna Inc, 200 Technology Square, Cambridge, MA 02139, USA. Electronic address:

Fabry disease is an X-linked lysosomal storage disease caused by loss of alpha galactosidase A (α-Gal A) activity and is characterized by progressive accumulation of globotriaosylceramide and its analogs in all cells and tissues. Although enzyme replacement therapy (ERT) is considered standard of care, the long-term effects of ERT on renal and cardiac manifestations remain uncertain and thus novel therapies are desirable. We herein report preclinical studies evaluating systemic messenger RNA (mRNA) encoding human α-Gal A in wild-type (WT) mice, α-Gal A-deficient mice, and WT non-human primates (NHPs). Read More

Eur Heart J Cardiovasc Imaging 2019 Mar 16. Epub 2019 Mar 16.

Department of Advanced Biomedical Sciences, University of Naples Federico II, Via Pansini 5, Naples, Italy.

Aims: Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder associated with multi-organ dysfunction. While native myocardial T1 mapping by magnetic resonance (MR) allow non-invasive measurement of myocyte sphingolipid accumulation, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and MR are able to identify different pathological patterns of disease progression. We investigated the relationship between T1 mapping and 18F-FDG uptake by hybrid PET-MR cardiac imaging in AFD female patients. Read More

CNS Drugs 2019 Apr;33(4):315-325

Department of Pediatrics, Section Biochemistry, University Medical Center Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.

The neuronal ceroid lipofuscinoses comprise a group of neurodegenerative lysosomal storage disorders caused by mutations in at least 13 different genes and primarily affect the brain and the retina of children or young adults. The disorders are characterized by progressive neurological deterioration with dementia, epilepsy, loss of vision, motor disturbances, and early death. While various therapeutic strategies are currently being explored as treatment options for these fatal disorders, there is presently only one clinically approved drug that has been shown to effectively attenuate the progression of a specific form of neuronal ceroid lipofuscinosis, CLN2 disease (cerliponase alfa, a lysosomal enzyme infused into the brain ventricles of patients with CLN2 disease). Read More

Molecules 2019 Mar 12;24(5). Epub 2019 Mar 12.

Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA.

Niemann-Pick disease, type C1 (NPC1) is a rare, autosomal recessive, lipid storage disorder caused by mutations in . As a result, there is accumulation of unesterified cholesterol and sphingolipids in the late endosomal/lysosomal system. Clinically, patients can present with splenomegaly and hepatomegaly. Read More

Theranostics 2019 20;9(5):1387-1400. Epub 2019 Feb 20.

State Key Laboratory of Military Stomatology, National Clinical Research Center for Oral Diseases, Department of Oral Biology, Clinic of Oral Rare and Genetic Diseases, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, R.P. China.

Human encodes voltage-gated chloride channel 7 (ClC-7); mutations of lead to osteopetrosis which is characterized by increased bone mass and impaired osteoclast function. In our previous clinical practice, we noticed that osteopetrosis patients with mutations had some special deformities in craniofacial morphology and tooth dysplasia. It is unclear whether these phenotypes are the typical features of involved osteopetrosis and whether ClC-7 could regulate the development of craniofacial bone and tooth in some signaling pathways. Read More

Arterioscler Thromb Vasc Biol 2019 Mar 14:ATVBAHA119312136. Epub 2019 Mar 14.

From the Cardiometabolic Genomics Program, Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, New York.

Lysosomal acid lipase (LAL), encoded by the lipase A ( LIPA) gene, hydrolyzes cholesteryl esters and triglycerides to generate free fatty acids and cholesterol in the cell. The essential role of LAL in lipid metabolism has been confirmed in mice and human with LAL deficiency. In humans, loss-of-function mutations of LIPA cause rare lysosomal disorders, Wolman disease and cholesteryl ester storage disease, in which LAL enzyme-replacement therapy has shown significant benefits in a phase 3 clinical trial. Read More

Biol Chem 2018 Dec 1. Epub 2018 Dec 1.

Department of Medical Genetics and Applied Genomics, University of Tübingen, Calwerstr. 7, D-72076 Tübingen, Germany.

Beta-glucosidase 2 (GBA2) is deficient in a form of human spastic paraplegia due to defects in the GBA2 (SPG46) gene. GBA2 was proposed as a modifier of Gaucher disease (lysosomal storage disease by deficient β-glucosidase 1; GBA1). Described assays of GBA2 activity mostly used artificial substrates incompletely modelling the situation with natural substrates in vivo. Read More

Cells 2019 Mar 11;8(3). Epub 2019 Mar 11.

Molecular Neuroscience Research Center, Shiga University of Medical Science, Otsu 520-2192, Japan.

Neurodegenerative diseases such as Alzheimer's disease have proven resistant to new treatments. The complexity of neurodegenerative disease mechanisms can be highlighted by accumulating evidence for a role for a growth factor, progranulin (PGRN). PGRN is a glycoprotein encoded by the GRN/Grn gene with multiple cellular functions, including neurotrophic, anti-inflammatory and lysosome regulatory properties. Read More