Search Our Scientific Publications & Authors

Ochsner J 2018 ;18(4):413-416

Department of Pediatrics, Ochsner Hospital for Children, Ochsner Clinic Foundation, New Orleans, LA.

Background: Pompe disease is a lysosomal storage disorder that results from an inborn error of metabolism involving abnormal glycogen storage. Infantile-onset Pompe disease is the most severe phenotype, and enzyme replacement therapy with alglucosidase alfa (Lumizyme) improves medical and functional outcomes in patients with infantile-onset Pompe disease.

Case Report: We report the case of a patient with infantile-onset Pompe disease who presented with severe hypertrophic cardiomyopathy, systolic and diastolic cardiac dysfunction, and hypotonia. Read More

Postgrad Med J 2018 Dec 17. Epub 2018 Dec 17.

Department of Internal Medicine, Divisions of Nephrology and Cardiology, University Hospital Würzburg, Würzburg, Germany

Fabry disease is a rare inborn error of the enzyme α-galactosidase (α-Gal) and results in lysosomal substrate accumulation in tissues with a wide range of clinical presentations. The disease has attracted a lot of interest over the last years, in particular since enzyme replacement therapy (ERT) has become widely available in 2001. With rising awareness and rising numbers of (diagnosed) patients, physicians encounter new challenges. Read More

Mov Disord 2018 Dec 17. Epub 2018 Dec 17.

Department of Pediatric and Adult Movement Disorders and Neuropsychiatry, Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.

There are several hundred single-gene disorders that we classify as inborn errors of metabolism. Inborn errors of metabolism are often rare and highly heterogeneous multisystem diseases with non-neurological and neurological manifestations, commonly with onset during childhood. Movement disorders are among the most common neurological problems in inborn errors of metabolism, but, in many cases, remain poorly defined. Read More

Nephron 2018 Dec 14;141(2):1-14. Epub 2018 Dec 14.

Department of Development and Regeneration, Organ Systems Cluster, KU Leuven, Leuven,

Mutations in the CTNS gene encoding the lysosomal membrane cystine transporter cystinosin are the cause of cystinosis, an autosomal recessive lysosomal storage disease. More than 140 CTNS mutations have been reported worldwide. Recent studies have discovered that cystinosin exerts other key cellular functions beyond cystine transport such as regulation of oxidative state, lysosomal dynamics and autophagy. Read More

FEBS J 2018 Dec 15. Epub 2018 Dec 15.

Department of Biochemistry and Groupe de Recherche Axé sur la Structure des Protéines, McGill University, Montreal, QC, H3G 0B1, Canada.

β-mannosidase is a lysosomal enzyme from the glycosyl hydrolase family 2 that cleaves the single β(1-4)-linked mannose at the non-reducing end of N-glycosylated proteins, and plays an important role in the polysaccharide degradation pathway. Mutations in the MANBA gene, which encodes the β-mannosidase, can lead to the lysosomal storage disease β-mannosidosis, as well as nystagmus, an eye condition characterized by involuntary eye movements. Here, we present the first structures of a mammalian β-mannosidase in both the apo and mannose-bound forms. Read More

Pediatr Int 2018 Dec 13. Epub 2018 Dec 13.

Department of Clinical Diagnosis, National Center for Child Health and Development, Tokyo.

Background: Mucopolysaccharidosis (MPS) VI is a rare, autosomal recessive congenital metabolic disorder caused by deficient activity of the lysosomal metabolic enzyme, N-acetylgalactosamine 4-sulfatase. Enzyme replacement therapy (ERT) is current therapeutic treatment for MPS VI, while involves limited compliance to the therapy and high costs. This study aimed to develop a new method of treatment by conducting an orthotopic liver transplantation using an animal model of human MPS VI, and to evaluate and examine its effectiveness for treating MPS VI. Read More

Mol Genet Genomic Med 2018 Dec 11. Epub 2018 Dec 11.

Paediatric Neurology Unit, Department of Paediatrics, UZ Brussel, Brussels, Belgium.

Background: The diagnostic workup in patients with a clinical suspicion of lysosomal storage diseases (LSD) is often difficult due to the variability in the clinical phenotype. The gold standard for diagnosis of LSDs consists of enzymatic testing. However, due to the sequential nature of this methodology and inconsistent genotype-phenotype correlations of certain LSDs, finding a diagnosis can be challenging. Read More

BMC Neurol 2018 Dec 12;18(1):203. Epub 2018 Dec 12.

FRIGE's Institute of Human Genetics, FRIGE House, Jodhpur Gam Road, Satellite, Ahmedabad, Gujarat, 380015, India.

Background: Neuronal ceroid lipofuscinoses type I and type II (NCL1 and NCL2) also known as Batten disease are the commonly observed neurodegenerative lysosomal storage disorder caused by mutations in the PPT1 and TPP1 genes respectively. Till date, nearly 76 mutations in PPT1 and approximately 140 mutations, including large deletion/duplications, in TPP1 genes have been reported in the literature. The present study includes 34 unrelated Indian patients (12 females and 22 males) having epilepsy, visual impairment, cerebral atrophy, and cerebellar atrophy. Read More

Front Physiol 2018 20;9:1663. Epub 2018 Nov 20.

Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.

Tay-Sachs disease belongs to the group of autosomal-recessive lysosomal storage metabolic disorders. This disease is caused by β-hexosaminidase A (HexA) enzyme deficiency due to various mutations in α-subunit gene of this enzyme, resulting in GM2 ganglioside accumulation predominantly in lysosomes of nerve cells. Tay-Sachs disease is characterized by acute neurodegeneration preceded by activated microglia expansion, macrophage and astrocyte activation along with inflammatory mediator production. Read More

Rev Gastroenterol Peru 2018 Jul-Sep;38(3):280-284

Facultad de Medicina Humana, Universidad Nacional San Luis Gonzaga. Ica, Perú; Sociedad Científica de Estudiantes de Medicina de Ica (SOCEMI). Ica, Perú.

Gaucher disease is an autosomal recessive lysosomal storage disorder characterized by deficiency of beta-glucosidase that would lead to the accumulation of glucosylceramide mainly in cells of the mononuclear phagocytic system causing systemic effectations. We present a patient of twenty years who is suffering from chronic pain in the left hypochondrium with episodes of bleeding for 3 years and sensation of thermal rise, physical examination revealed jaundice and massive splenomegaly, without neurological involvement. Severe osteoporosis, pancytopenia, and the presence of portal vein thrombosis with cavernomatous transformation complicated by portal biliopathy simulating a klatskin tumor, marrow and enzymatic studies were compatible with Gaucher disease, were shown as unexpected findings. Read More

EMBO J 2018 Dec 7. Epub 2018 Dec 7.

Department of Molecular Neuropathology, Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Madrid, Spain

Neuropathic lysosomal storage disorders (LSDs) present with activated pro-inflammatory microglia. However, anti-inflammatory treatment failed to improve disease pathology. We characterise the mechanisms underlying microglia activation in Niemann-Pick disease type A (NPA). Read More

Mol Genet Metab 2018 Dec 3. Epub 2018 Dec 3.

NIH Undiagnosed Diseases Program, Common Fund, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States; Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States. Electronic address:

CLN6 is a transmembrane protein located in the endoplasmic reticulum that is involved in lysosomal acidification. Mutations in CLN6 cause late-infantile neuronal ceroid lipofuscinosis (LINCL), and teenage and adult onset NCL without visual impairment. Here we describe two pediatric patients with LINCL from unrelated families who were evaluated at the National Institutes of Health. Read More

Trends Endocrinol Metab 2018 Dec 6. Epub 2018 Dec 6.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA; Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:

The pathogenic mechanisms underlying Parkinson's disease (PD)/parkinsonism affect mitochondrial and endolysosomal trafficking. The retromer is required to retrieve some proteins from endosomes to the Golgi and plasma membrane. Here, we discuss how retromer-dependent retrieval also affects ceramide metabolism. Read More

Mol Genet Metab 2018 Nov 22. Epub 2018 Nov 22.

Department of Biological Sciences, Simon Fraser University, 8888 University Dr., Burnaby B.C. V5A 1S6, Canada. Electronic address:

Small-molecule- enzyme enhancement therapeutics (EETs) have emerged as attractive agents for the treatment of lysosomal storage diseases (LSDs), a broad group of genetic diseases caused by mutations in genes encoding lysosomal enzymes, or proteins required for lysosomal function. The underlying enzyme deficiencies characterizing LSDs cause a block in the stepwise degradation of complex macromolecules (e.g. Read More

Methods Mol Biol 2019 ;1885:233-250

Mount Sinai Genomics, Inc., DBA Sema 4, New York, NY, USA.

Tay-Sachs disease (TSD) is an autosomal recessive lysosomal storage disorder caused by mutations of the HEXA gene resulting in the deficiency of hexosaminidase A (Hex A) and subsequent neuronal accumulation of G gangliosides. Infantile TSD is a devastating and fetal neurodegenerative disease with death before the age of 3-5 years. A small proportion of TSD patients carry milder mutations and may present juvenile or adult onset milder disease. Read More

Mol Genet Metab 2018 Nov 29. Epub 2018 Nov 29.

Stony Brook University, School of Medicine, Stony Brook, NY, USA.

Background: Acid sphingomyelinase deficiency (ASMD), a rare lysosomal storage disease, results from mutations in SMPD1, the gene encoding acid sphingomyelinase (ASM). As a result, sphingomyelin accumulates in multiple organs including spleen, liver, lung, bone marrow, lymph nodes, and in the most severe form, in the CNS and peripheral nerves. Clinical manifestations range from rapidly progressive and fatal infantile neurovisceral disease, to less rapidly progressing chronic neurovisceral and visceral forms that are associated with significant morbidity and shorter life span due to respiratory or liver disease. Read More

Nat Nanotechnol 2018 Dec 3. Epub 2018 Dec 3.

Department of Chemistry, The University of Chicago, Chicago, IL, USA.

Lysosomes are multifunctional, subcellular organelles with roles in plasma membrane repair, autophagy, pathogen degradation and nutrient sensing. Dysfunctional lysosomes underlie Alzheimer's disease, Parkinson's disease and rare lysosomal storage diseases, but their contributions to these pathophysiologies are unclear. Live imaging has revealed lysosome subpopulations with different physical characteristics including dynamics, morphology or cellular localization. Read More

Adv Neonatal Care 2018 Dec;18(6):480-487

West Chester University, West Chester, Pennsylvania (Dr Joseph and Ms DiCesare); and Nemours/A. I. duPont Hospital for Children, Wilmington, Delaware (Ms Miller).

Background: Hunter syndrome, or mucopolysaccharidosis type II (MPS II), is a lysosomal storage disease that affects the breakdown of sugar in the body. Research has made it possible to reveal the cause of the disease, thus helping diagnose and treating this rare disorder. Enzyme replacement therapy will help children live longer and healthier lives. Read More

J Hum Genet 2018 Nov 29. Epub 2018 Nov 29.

Division of Gene Therapy, Research Center for Medical Sciences/Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.

Gene therapies for lysosomal storage diseases (LSD) and peroxisomal diseases (PD) are rapidly advancing. Most LSDs and PDs are characterized by brain involvement, prompting the development of therapies targeting the brain. There are two types of gene therapy for brain involvement in LSD and PD, i. Read More

EBioMedicine 2018 Nov 27. Epub 2018 Nov 27.

Orphazyme A/S, Ole Maaloes vej 3, DK-2200 Copenhagen, Denmark. Electronic address:

Background: Gaucher Disease is caused by mutations of the GBA gene which encodes the lysosomal enzyme acid beta-glucosidase (GCase). GBA mutations commonly affect GCase function by perturbing its protein homeostasis rather than its catalytic activity. Heat shock proteins are well known cytoprotective molecules with functions in protein homeostasis and lysosomal function and their manipulation has been suggested as a potential therapeutic strategy for GD. Read More

Brain 2018 Dec;141(12):3428-3442

Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK.

Mutations in the endosome-associated protein CHMP2B cause frontotemporal dementia and lead to lysosomal storage pathology in neurons. We here report that physiological levels of mutant CHMP2B causes reduced numbers and significantly impaired trafficking of endolysosomes within neuronal dendrites, accompanied by increased dendritic branching. Mechanistically, this is due to the stable incorporation of mutant CHMP2B onto neuronal endolysosomes, which we show renders them unable to traffic within dendrites. Read More

Mov Disord 2018 Nov 28. Epub 2018 Nov 28.

University of Groningen, Division of Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands.

Inborn errors of metabolism in adults are still largely unexplored. Despite the fact that adult-onset phenotypes have been known for many years, little attention is given to these disorders in neurological practice. The adult-onset presentation differs from childhood-onset phenotypes, often leading to considerable diagnostic delay. Read More

J Appl Toxicol 2018 Nov 28. Epub 2018 Nov 28.

Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup, Jellobuk-do, Republic of Korea.

Cigarette smoke is known to be associated with the incidence of a variety of pulmonary diseases, and alveolar macrophages are a key player in the defense mechanism against inhalable toxicants. Herein, we have found that a hydrophilic fraction in smoke extracts from 3R4F reference cigarettes (CSE) contains high concentrations of volatile substances compared to cigarette smoke condensate (amphoteric fraction). We also identified the toxic mechanism of CSE using MH-S, a mouse alveolar macrophage cell line. Read More

Int J Mol Sci 2018 Nov 23;19(12). Epub 2018 Nov 23.

Institute of Biomedicine and Molecular Immunology "A. Monroy", National Research Council, 90146 Palermo, Italy.

Anderson-Fabry disease (FD) is a rare, progressive, multisystem storage disorder caused by the partial or total deficit of the lysosomal enzyme α-galactosidase A (α-Gal A). It is an X-linked, lysosomal enzymopathy due to mutations in the galactosidase alpha gene (GLA), encoding the α-Gal A. To date, more than 900 mutations in this gene have been described. Read More

Elife 2018 11 26;7. Epub 2018 Nov 26.

Harvard Medical School, Harvard University, Boston, United States.

Pain behaviors in a Fabry mouse model are associated with the accumulation of a fat molecule that disrupts sodium ion channels in small fiber neurons. Read More

Blood Cells Mol Dis 2018 Aug 10. Epub 2018 Aug 10.

Ege University Medical Faculty, Pediatric Metabolism Department, İzmir, Turkey.

Gaucher Disease (GD) is the most common lysosomal storage disorder has traditionally been classified into three clinical phenotypes. Type 3 GD is characterized by neurological involvement but neurological symptoms generally appear later in life than in type 2 disease. Neutropenia is much rarer than other hematological manifestations in GD and has not been scrutinized adequately. Read More

Mol Genet Metab 2018 Nov 17. Epub 2018 Nov 17.

Amsterdam UMC, University of Amsterdam, Department of Endocrinology and Metabolism, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Electronic address:

Background: Treatment of Fabry disease (FD) with recombinant alpha-galactosidase A (r-αGAL A) is complicated by the formation of anti-drug antibodies in the majority of male patients with the classical disease phenotype. Detailed information regarding antibody subtypes, onset and persistence of antibody development and their effect on treatment efficacy is sparse.

Methods: A retrospective study was carried out in 39 male patients with classical FD, treated with either agalsidase-alfa or agalsidase-beta (mean follow up of 10 years). Read More

Am J Pathol 2018 Nov 22. Epub 2018 Nov 22.

Institute of Medical Science, University of Toronto, Toronto Canada; Department of Pediatrics, Medical College of Wisconsin, Milwaukee USA; Department of Medical Biophysics, University of Toronto, Toronto, Canada; Department of Biochemistry, Medical College of Wisconsin, Milwaukee USA; University Health Network, Toronto, Canada. Electronic address:

Farber Disease (FD) is a debilitating lysosomal storage disorder characterized by severe inflammation and neurodegeneration. FD is caused by mutations in the ASAH1 gene resulting in deficient acid ceramidase (ACDase) activity. Patients with ACDase deficiency exhibit a broad clinical spectrum. Read More

Kidney Int 2018 Nov 20. Epub 2018 Nov 20.

Division of Nephrology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, USA. Electronic address:

Fabry disease results from loss of activity of the lysosomal enzyme α-galactosidase A (GLA), leading to the accumulation of globoseries glycosphingolipids in vascular endothelial cells. Thrombosis and stroke are life-threatening complications of Fabry disease; however, the mechanism of the vasculopathy remains unclear. We explored the relationship between GLA deficiency and endothelial cell von Willebrand factor (VWF) secretion in in vivo and in vitro models of Fabry disease. Read More

Ther Umsch 2018 Nov;75(4):217-224

3 Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Universitätsspital Zürich, Zürich.

Fabry disease - the profile of an orphan disease Abstract. Fabry disease is a lysosomal storage disease, characterized by a deficient lysosomal function. The main pathophysiological mechanism is the deficiency of the enzyme α-galactosidase A. Read More

Ther Umsch 2018 Nov;75(4):199-207

3 Universitätsspital Zürich, Klinik für Endokrinologie, Diabetologie und Klinische Ernährung, Zürich.

The basics of lysosomal storage diseases Abstract. Lysosomal storage diseases are comprised of a group of more than 50 genetic disorders which are characterized by a defective lysosomal function. The lysosome is the recycling plant of the cell. Read More

J Ayub Med Coll Abbottabad 2018 Jul-Sep;30(3):479-481

Civil Hospital Karachi, Pakistan.

Gaucher's disease is the most common lysosomal storage disease which occurs due to a deficiency of the enzyme glucocerebrosidase. This enzyme deficiency leads to accumulation of glucocerebrosidase in the cells of macrophage-monocyte system. It is inherited as an autosomal recessive mutation and has three clinical subtypes. Read More

Int Heart J 2018 Nov 20. Epub 2018 Nov 20.

Department of Cardiology, Showa University Fujigaoka Hospital.

Anderson-Fabry disease is a rare X-linked lysosomal storage disease caused by α-galactosidase A (α-GalA) gene variants and characterized by a large genotypic and phenotypic spectrum. Enzyme replacement therapy (ERT) using recombinant α-GalA has been approved for > 10 years as a specific therapy for the disease. However, the long-term clinical efficacy for cardiac manifestations has been equivocal because it depends on several factors such as genotype, sex, age, and disease severity at the initiation of ERT. Read More

Medicine (Baltimore) 2018 Nov;97(47):e13161

Department of Hematology, Gui Zhou Provincial People's Hospital.

Rationale: Gaucher disease (GD), characterized by glucosylceramide accumulation in the macrophage-monocyte system, is caused by glucosidase b acid (GBA) gene mutations which lead to the deficiency of lysosomal enzyme glucocerebrosidase. The mutation spectrum of GBA in Chinese patients is quite different from those seen in Jewish and non-Jewish Caucasian patients. Thus, it is relatively hard to diagnose GD in Chinese. Read More

Dis Model Mech 2018 Nov 20;11(11). Epub 2018 Nov 20.

Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Kolkata, Mohanpur 741246, West Bengal, India

Mucopolysaccharidosis VII (MPS VII) is a recessively inherited lysosomal storage disorder caused by β-glucuronidase enzyme deficiency. The disease is characterized by widespread accumulation of non-degraded or partially degraded glycosaminoglycans, leading to cellular and multiple tissue dysfunctions. The patients exhibit diverse clinical symptoms, and eventually succumb to premature death. Read More

Gene 2018 Nov 17;686:261-269. Epub 2018 Nov 17.

Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

Background: Mucopolysaccharidosis type IVA (MPS IVA) is a rare autosomal recessive lysosomal storage disorder caused by GALNS gene mutation. The aim of our study is to detect pathogenic variants for patients suspected of MPS IVA and set the base for subsequent prenatal diagnosis and preimplantation genetic diagnosis.

Methods: In our study, 9 MPS IVA patients from south China families were investigated. Read More

Biochim Biophys Acta Mol Basis Dis 2018 Nov 16;1865(2):322-328. Epub 2018 Nov 16.

Division of Biology, Kansas State University, Manhattan, KS 66506, USA; Graduate Biochemistry Group, Kansas State University, Manhattan, Kansas 66506, USA. Electronic address:

The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative lysosomal storage disorders. CLN8 deficiency causes a subtype of NCL, referred to as CLN8 disease. CLN8 is an ER resident protein with unknown function; however, a role in ceramide metabolism has been suggested. Read More

J Neurochem 2018 Nov 19. Epub 2018 Nov 19.

Stem Cell and Neurotherapies, Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.

Mucopolysaccharidoses are lysosomal storage disorders characterised by accumulation of abnormal pathological glycosaminoglycans, cellular dysfunction and widespread inflammation, resulting in progressive cognitive and motor decline. Lysosomes are important mediators of immune cell function, and therefore accumulation of glycosaminoglycans (GAGs) and other abnormal substrates could affect immune function and directly impact on disease pathogenesis. This review summarises current knowledge with regard to inflammation in mucopolysaccharidosis, with an emphasis on the brain and outlines a potential role for GAGs in induction of inflammation. Read More

Neurobiol Dis 2018 Nov 15;124:152-162. Epub 2018 Nov 15.

Departments of Neurology and Neurobiology, Center for Neurodegeneration and Experimental Therapeutics, Alzheimer's Disease Center, Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL, United States. Electronic address:

Loss-of-function mutations in progranulin (GRN), most of which cause progranulin haploinsufficiency, are a major autosomal dominant cause of frontotemporal dementia (FTD). Individuals with loss-of-function mutations on both GRN alleles develop neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disorder. Progranulin is a secreted glycoprotein expressed by a variety of cell types throughout the body, including neurons and microglia in the brain. Read More

Ital J Pediatr 2018 Nov 16;44(Suppl 2):124. Epub 2018 Nov 16.

Department of Translational Medical Sciences, Federico II University, Naples, Italy.

Enzyme replacement therapy is currently considered the standard of care for the treatment of mucopolysaccharidoses (MPS) type I, II, VI, and IV. This approach has shown substantial efficacy mainly on somatic symptoms of the patients, but no benefit was found for other clinical manifestations, such as neurological involvement. New strategies are currently being tested to address these limitations, in particular to obtain sufficient therapeutic levels in the brain. Read More

Ital J Pediatr 2018 Nov 16;44(Suppl 2):128. Epub 2018 Nov 16.

Clinica Pediatrica, Fondazione MBBM, Università Milano-Bicocca, Monza, Italy.

A new patient with severe mucopolysaccharidosis (MPS) type VII is reported. Non-immune hydrops fetalis (NIHF) was diagnosed during pregnancy. At birth, he showed generalized hydrops and dysmorphic features typical of MPS. Read More

Ital J Pediatr 2018 Nov 16;44(Suppl 2):121. Epub 2018 Nov 16.

UOS Malattie Metaboliche Rare, Clinica Pediatrica, Fondazione MBBM, ATS Monza, Monza, Italy.

Mucopolysaccharidoses (MPS) are a group of lysosomal multisystemic, chronic, and progressive diseases characterized by the storage of glycosaminoglycans (GAGs) that may affect the central nervous system. Neuronopathic MPS such as MPS IH, MPS II, MPS IIIA-D, and MPS VII are characterized by neurocognitive regression. In severe MPS I (MPS IH, or Hurler syndrome) initial developmental trajectory is usually unremarkable but cognitive development shows a plateau by 2 to 4 years of age and then progressively regresses with aging. Read More

Ital J Pediatr 2018 Nov 16;44(Suppl 2):130. Epub 2018 Nov 16.

San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20123, Milan, Italy.

Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by a deficiency in lysosomal enzymes catalyzing the stepwise degradation of glycosaminoglycans (GAGs). The current therapeutic strategies of enzyme replacement therapy and allogeneic hematopoietic stem cell transplantation have been reported to reduce patient morbidity and to improve their quality of life, but they are associated with persistence of residual disease burden, in particular at the neurocognitive and musculoskeletal levels. This indicates the need for more efficacious treatments capable of effective and rapid enzyme delivery to the affected organs, especially the brain and the skeleton. Read More

Ital J Pediatr 2018 Nov 16;44(Suppl 2):125. Epub 2018 Nov 16.

Department of Ophthalmology, Ospedale San Gerardo, Via G. B. Pergolesi 33, 20052, Monza, MB, Italy.

Mucopolysaccharidoses (MPS) are a group of rare lysosomal storage disorders characterized by the accumulation of glycosaminoglycans (GAGs) in different parts of the eye. Ocular problems are very common in MPS children, and the cornea, sclera, trabecular meshwork, retina, and optic nerve may all be involved. Early diagnosis is very important to preserve the visual function, and the diagnosis requires experience and different evaluations. Read More

Ital J Pediatr 2018 Nov 16;44(Suppl 2):122. Epub 2018 Nov 16.

U.O. Cardiologia Pediatrica e U.O. di Riabilitazione e Scompenso Cardiaco, Ospedale Monaldi, A.O. dei Colli, Dipartimento di Scienze Cardio-Toraciche e Respiratorie, Università della Campania Luigi Vanvitelli, Via Leonardo Bianchi, 80131, Naples, Italy.

Mucopolysaccharidoses (MPS) are a group of hereditary disorders caused by lysosomal storage of glycosaminoglycans (GAGs) and characterized by a wide variability of phenotypes from severe fetal-neonatal forms to attenuated diseases diagnosed in adult individuals. The clinical picture generally worsens with age due to progressive storage involving mucosal tissue, upper airways and lungs, bones and joints, central and peripheral nervous system, heart, liver, eye, and ear. Cardiac storage of GAGs involves valves, heart muscle, and vessels (particularly the coronary arteries), and can be specific in relation to different MPS types and enzyme defects. Read More

Ital J Pediatr 2018 Nov 16;44(Suppl 2):129. Epub 2018 Nov 16.

Neuroscience Department, Molecular and Cell Biology Laboratory of Neurometabolic Diseases, Meyer Children's Hospital, University of Florence, Florence, Italy.

Mucopolysaccharidoses (MPS) are rare inherited disorders caused by a deficit of the lysosomal hydrolases involved in the degradation of mucopolysaccharides, also known as glycosaminoglycans (GAGs). They are all monogenic defects, transmitted in an autosomal recessive way, except for MPS type II which is X-linked. The enzymatic deficit causes a pathologic accumulation of undegraded or partially degraded substrates inside lysosomes as well as in the extracellular compartment. Read More

Ital J Pediatr 2018 Nov 16;44(Suppl 2):126. Epub 2018 Nov 16.

Division of Inherited Metabolic Diseases, Regional Center for Expanded Neonatal Screening, Department of Women and Children's Health, University Hospital of Padova, Via Orus 2/B, 35129, Padova, Italy.

Newborn screening (NBS) methods and therapeutic options have become increasingly available for mucopolysaccharidoses (MPS), and there is a clear evidence that early intervention significantly improves the outcome. It is recommended that mucopolysaccharidosis type I (MPS I) is included in the US newborn screening panel, and this is currently underway in some NBS programs in the world. The key factors in recommending MPS I for inclusion in NBS are the strongly improved efficacy of early-onset therapy and the improved performance of screening tests. Read More

Trends Biochem Sci 2018 Nov 10. Epub 2018 Nov 10.

Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:

Lysosomes, the degradation center of the cell, are filled with acidic hydrolases. Lysosomes generate nutrient-sensitive signals to regulate the import of H, hydrolases, and endocytic and autophagic cargos, as well as the export of their degradation products (catabolites). In response to environmental and cellular signals, lysosomes change their positioning, number, morphology, size, composition, and activity within minutes to hours to meet the changing cellular needs. Read More

Int J Mol Sci 2018 Nov 12;19(11). Epub 2018 Nov 12.

Department of Anatomy, University of Rostock, 18057 Rostock, Germany.

Introduction: Olfactory impairment is one of the earliest symptoms in neurodegenerative disorders that has also been documented in Niemann-Pick disease type C1 (NPC1). NPC1 is a very rare, neurovisceral lipid storage disorder, characterized by a deficiency of gene function that leads to progressive neurodegeneration. Here, we compared the pathologic effect of defective gene on the vomeronasal neuroepithelium (VNE) with that of the olfactory epithelium (OE) in an NPC1 mouse model. Read More

Autophagy 2018 Nov 13:1-16. Epub 2018 Nov 13.

a Life Sciences Institute, and Department of Molecular, Cellular and Developmental Biology , University of Michigan , Ann Arbor , MI , USA.

Hydrolysis within the vacuole in yeast and the lysosome in mammals is required for the degradation and recycling of a multitude of substrates, many of which are delivered to the vacuole/lysosome by autophagy. In humans, defects in lysosomal hydrolysis and efflux can have devastating consequences, and contribute to a class of diseases referred to as lysosomal storage disorders. Despite the importance of these processes, many of the proteins and regulatory mechanisms involved in hydrolysis and efflux are poorly understood. Read More