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Nat Rev Neurol 2019 Feb 19. Epub 2019 Feb 19.

Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD, USA.

Batten disease (also known as neuronal ceroid lipofuscinoses) constitutes a family of devastating lysosomal storage disorders that collectively represent the most common inherited paediatric neurodegenerative disorders worldwide. Batten disease can result from mutations in 1 of 13 genes. These mutations lead to a group of diseases with loosely overlapping symptoms and pathology. Read More

Expert Rev Endocrinol Metab 2011 Nov;6(6):755-768

a Department of Medical Genetics, University of British Columbia, Child and Family Research Institute, 4500 Oak Street, RM C234, Vancouver, British Columbia, V6H-3N1, Canada.

A decade has passed since the initial report that parenteral use of recombinant human α-L-iduronidase results in amelioration of symptoms in patients with mucopolysaccharidosis type I (MPS I). As a result, MPS I became the first mucopolysaccharide storage disorder to benefit from enzyme replacement therapy (ERT); subsequent ERTs have been approved for MPS II and VI. The ability of lysosomal storage disorders to respond to ERT is unique among genetic disorders and relates to the capability of cells to take up recombinant lysosomal enzymes through cell surface receptors and deliver them to the lysosome, a processed coined as 'cross-correction'. Read More

Int J Mol Sci 2019 Feb 15;20(4). Epub 2019 Feb 15.

Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2C, 15-222 Bialystok, Poland.

There is a rising number of evidence indicating the increased risk of cancer development in association with congenital metabolic errors. Although these diseases represent disorders of individual genes, they lead to the disruption of metabolic pathways resulting in metabolite accumulation or their deficiency. Gaucher disease (GD) is an autosomal recessive sphingolipidosis. Read More

Elife 2019 Feb 18;8. Epub 2019 Feb 18.

Institute of Cellular Biochemistry, University Medical Center Goettingen, Goettingen, Germany.

Perturbations in mitochondrial function and homeostasis are pervasive in lysosomal storage diseases, but the underlying mechanisms remain unknown. Here, we report a transcriptional program that represses mitochondrial biogenesis and function in lysosomal storage diseases Niemann-Pick type C (NPC) and acid sphingomyelinase deficiency (ASM), in patient cells and mouse tissues. This mechanism is mediated by the transcription factors KLF2 and ETV1, which are both induced in NPC and ASM patient cells. Read More

Front Endocrinol (Lausanne) 2019 1;10:21. Epub 2019 Feb 1.

Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, United States.

Cystinosis is a lysosomal storage disorder caused by defects in , the gene that encodes the lysosomal cystine transporter cystinosin. Patients with nephropathic cystinosis are characterized by endocrine defects, defective proximal tubule cell (PTC) function, the development of Fanconi syndrome and, eventually, end-stage renal disease. Kidney disease is developed despite the use of cysteamine, a drug that decreases lysosomal cystine overload but fails to correct overload-independent defects. Read More

Cell Signal 2019 Feb 13. Epub 2019 Feb 13.

Department of Biology, Trent University, Peterborough, Ontario, Canada.

Mutations in CLN3 cause a juvenile form of neuronal ceroid lipofuscinosis (NCL). This devastating neurological disorder, commonly known as Batten disease, is currently untreatable due to a lack of understanding of the physiological role of the protein. Recently, work in the social amoeba Dictyostelium discoideum has provided valuable new insight into the function of CLN3 in the cell. Read More

Clin Chim Acta 2019 Feb 13;492:69-71. Epub 2019 Feb 13.

Metabolic Laboratory, Center of Diagnostics, Hamburg, Germany; NCL Clinic, Department of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany. Electronic address:

Purpose: CLN2 disease is a genetic disorder caused by dysfunction of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1) that belongs to the neuronal ceroid lipofuscinoses (NCL) and leads to epilepsy, dementia, and death in young persons. CLN2 disease has recently become treatable by enzyme replacement, which can only be effective when the disease is diagnosed early. We have investigated the reliability of a test for TPP1 deficiency in dried blood specimens (DBS) to detect CLN2 disease. Read More

Neuromuscul Disord 2018 Dec 17. Epub 2018 Dec 17.

Erasmus Medical Center, Pompe Center, Rotterdam, The Netherlands.

This multicenter/multinational, open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat-dose avalglucosidase alfa (neoGAA), a second-generation, recombinant acid α-glucosidase replacement therapy, in late-onset Pompe disease (LOPD). Patients ≥18 years, alglucosidase alfa naïve (Naïve) or previously receiving alglucosidase alfa for ≥9 months (Switch), with baseline FVC ≥50% predicted and independently ambulatory, received every-other-week avalglucosidase alfa 5, 10, or 20 mg/kg over 24 weeks. 9/10 Naïve and 12/14 Switch patients completed the study. Read More

Neuromuscul Disord 2018 Dec 15. Epub 2018 Dec 15.

Unidad de Oncogenética Molecular, Instituto de Genética Médica y Molecular (INGEMM), Edificio Quirúrgico Planta-2, Hospital Universitario La Paz, 28046 Madrid, Spain; Department of Biochemistry, Faculty of Medicine, Autonoma University of Madrid, 28046 Madrid, Spain. Electronic address:

Glycogen storage disease type II, or Pompe disease, is an autosomal recessive disorder caused by deficiency of lysosomal acid alpha-glucosidase (GAA). We performed genetic analysis to confirm the diagnosis of Pompe disease in a 61-year-old patient with progressive weakness in extremities, severe Sleep Apnea-Hypopnea Syndrome, a significant reduction of alpha-glucosidase in liquid sample of peripheral blood and muscular biopsy diagnosis. GAA gene sequencing showed the patient is homozygous for the splice-site mutation c. Read More

BMC Med Genet 2019 Feb 14;20(1):31. Epub 2019 Feb 14.

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

Background: Gaucher disease is a rare pan-ethnic, lysosomal storage disorder resulting due to beta-Glucosidase (GBA1) gene defect. This leads to the glucocerebrosidase enzyme deficiency and an increased accumulation of undegraded glycolipid glucocerebroside inside the cells' lysosomes. To date, nearly 460 mutations have been described in the GBA1 gene. Read More

J Child Neurol 2019 Feb 13:883073819828587. Epub 2019 Feb 13.

1 University of Florida, Departments of Pediatrics, Division of Genetics and Metabolism, Neuroscience and Molecular Genetics & Microbiology, Gainesville, FL, USA.

The leukodystrophies are a group of genetic metabolic diseases characterized by an abnormal development or progressive degeneration of the myelin sheath. The myelin is a complex sheath composed of several macromolecules covering axons as an insulator. Each of the leukodystrophies is caused by mutations in genes encoding enzymes that are involved in myelin production and maintenance. Read More

Brain Dev 2019 Feb 9. Epub 2019 Feb 9.

Department of Clinical Laboratory Medicine, National Center for Child Health and Development, Tokyo, Japan.

Mucopolysaccharidosis type IH (MPS IH, Hurler syndrome) is a progressive, multisystem autosomal recessive lysosomal storage disorder resulting in the consequent accumulation of glycosaminoglycans. It is well recognized that early hematopoietic stem cell transplantation (HSCT) prevents neurocognitive decline in MPS IH. We followed the divergent clinical course in two Japanese siblings with MPS IH. Read More

Int J Mol Sci 2019 Feb 11;20(3). Epub 2019 Feb 11.

Division of Pulmonary Medicine, Department of Pediatric, Duke University School of Medicine, Durham, NC 27710, USA.

The authors of the recently published, "Molecular Pathways and Respiratory Involvement in Lysosomal Storage Diseases", provide an important review of the various mechanisms of lysosomal storage diseases (LSD) and how they culminate in similar clinical pathologies [... Read More

J Clin Med 2019 Feb 8;8(2). Epub 2019 Feb 8.

Reference Centre of Lysosomal Diseases, University Hospital Beaujon, 100 Boulevard du Général Leclerc, 92110 Clichy, France.

Type 1 Gaucher disease is a rare genetic lysosomal disorder due to acid betaglucosidase deficiency. The main features are thrombocytopenia, anemia, hepatosplenomegaly and complex skeletal disease. Complications include pulmonary hypertension, cirrhosis and splenic infarction; comorbidities, such as autoimmune phenomena, B-cell malignancies and Parkinson disease also occur. Read More

Cell Death Dis 2019 Feb 11;10(2):121. Epub 2019 Feb 11.

Shanghai Key Laboratory of Diabetes, Shanghai Institute for Diabetes, Shanghai Clinical Medical Centre of Diabetes, Shanghai Key Clinical Centre of Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai JiaoTong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.

In obesity, adipocytes exhibit high metabolic activity accompanied by an increase in lipid mobilization. Recent findings indicate that autophagy plays an important role in metabolic homeostasis. However, the role of this process in adipocytes remains controversial. Read More

Rev Neurol 2019 Feb;68(4):155-159

Hospital de Ninos de la Santisima Trinidad, Cordoba, Argentina.

Introduction: CLN8 disease is one of the thirteen recognized genetic types of neuronal ceroid lipofuscinosis, a group of neurodegenerative lysosomal storage disorders, most frequent in childhood. A putative 286 amino acids transmembrane CLN8 protein with unknown function is affected. Pathological variants in the CLN8 gene were associated with two different phenotypes: variant late-infantile in individuals from many countries worldwide, and epilepsy progressive with mental retardation, appearing in Finnish and Turkish subjects. Read More

Ann Transl Med 2018 Dec;6(24):476

Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.

The lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders that are caused for the most part by enzyme deficiencies within the lysosome resulting in accumulation of undegraded substrate. This storage process leads to a broad spectrum of clinical manifestations depending on the specific substrate and site of accumulation. Examples of LSDs include the mucopolysaccharidoses, mucolipidoses, oligosaccharidoses, Pompe disease, Gaucher disease, Fabry disease, the Niemann-Pick disorders, and neuronal ceroid lipofuscinoses. Read More

Nephron 2019 Feb 8:1-8. Epub 2019 Feb 8.

Department of Nephrology, Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty, Istanbul,

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from lack of alpha-galactosidase A (AGALA) activity in lysosomes.

Objective: In this multicenter study, we aimed to evaluate the prevalence of FD in renal transplant (Tx) recipients in Turkey. We also screened dialysis patients as a control group. Read More

Clin Neuropathol 2019 Feb 10. Epub 2019 Feb 10.

Neutral lipid storage disease with myopathy (NLSDM) is a triglyceride metabolic disorder caused by defects of adipose triglyceride lipases (ATGL). The coexistence of lipid vacuoles and rimmed vacuoles in the myofibers is a characteristic pathological change in some NLSDM cases. However, it has not been explored whether autophagic abnormalities exist in the NLSDM myofibers with rimmed vacuole. Read More

Eur J Hum Genet 2019 Feb 8. Epub 2019 Feb 8.

Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands.

Analyses in our diagnostic DNA laboratory include genes involved in autosomal recessive (AR) lysosomal storage disorders such as glycogenosis type II (Pompe disease) and mucopolysaccharidosis type I (MPSI, Hurler disease). We encountered 4 cases with apparent homozygosity for a disease-causing sequence variant that could be traced to one parent only. In addition, in a young child with cardiomyopathy, in the absence of other symptoms, a diagnosis of Pompe disease was considered. Read More

Brain Dev 2019 Feb 5. Epub 2019 Feb 5.

Division of Neurology, National Center for Child Health and Development, Tokyo, Japan.

Background: Niemann-Pick type C (NPC) is a lysosomal lipid storage disease with mutation of NPC1/NPC2 genes, which transport lipids in the endosome and lysosome, and various neurological symptoms. NPC patients also develop hepatosplenomegaly or liver disorder in the neonatal period, and 10% suffer severe liver failure. Neonatal hemochromatosis (NH) is a liver disorder characterized by hepatic and extrahepatic siderosis. Read More

Cytokine Growth Factor Rev 2019 Jan 30. Epub 2019 Jan 30.

Department of Orthopaedic Surgery, New York University Medical Center, New York, NY, 10003, USA; Department of Cell Biology, New York University School of Medicine, New York, NY, 10016, USA. Electronic address:

Progranulin (PGRN), a widely expressed glycoprotein with pleiotropic function, has been linked to a host of physiological processes and diverse pathological states. A series of contemporary preclinical disease models and clinical trials have evaluated various therapeutic strategies targeting PGRN, highlighting PGRN as a promising therapeutic target. Herein we summarize available knowledge of PGRN targeting in various kinds of diseases, including common neurological diseases, inflammatory autoimmune diseases, cancer, tissue repair, and rare lysosomal storage diseases, with a focus on the functional domain-oriented drug development strategies. Read More

Orphanet J Rare Dis 2019 Feb 7;14(1):32. Epub 2019 Feb 7.

Actelion Pharmaceuticals Ltd., Allschwil, Switzerland.

Background: Niemann-Pick disease Type C (NP-C) is a lysosomal lipid storage disorder characterized by progressive neurodegenerative symptomatology. The signs and symptoms of NP-C vary with age at disease onset, and available therapies are directed at alleviating symptoms and stabilizing disease progression. We report the characteristics and factors related to disease progression, and analyze the effect of miglustat treatment on disease progression and patient survival using NP-C disability scales. Read More

J Audiol Otol 2019 Feb 8. Epub 2019 Feb 8.

Department of Otorhinolaryngology, Boramae Medical Center, Seoul Metropolitan Government-Seoul National University, Seoul, Korea.

Background And Objectives: The antioxidant ebselen will be able to limit or prevent the ototoxicity arising from 2-hydroxypropyl-β-cyclodextrin (HPβCD). Niemann-Pick Type C (NPC) disease is a disorder of lysosomal storage manifested in sphingolipidosis. Recently, it was noted that experimental use of HPβCD could partially resolve the symptoms in both animals and human patients. Read More

Mov Disord 2019 Feb 6. Epub 2019 Feb 6.

Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Lysosomal storage disorders comprise a clinically heterogeneous group of autosomal-recessive or X-linked genetic syndromes caused by disruption of lysosomal biogenesis or function resulting in accumulation of nondegraded substrates. Although lysosomal storage disorders are diagnosed predominantly in children, many show variable expressivity with clinical presentations possible later in life. Given the important role of lysosomes in neuronal homeostasis, neurological manifestations, including movement disorders, can accompany many lysosomal storage disorders. Read More

Mod Pathol 2019 Feb 5. Epub 2019 Feb 5.

Department of Pediatrics I, Inherited Metabolic Disorders, Medical University of Innsbruck, Innsbruck, Austria.

Both lysosomal storage diseases and mitochondrial diseases are a group of genetic-inherited metabolic disorders. In an era, where "old fashioned methods" are apparently being replaced by evolving molecular techniques (i.e. Read More

Brain Sci 2019 Feb 1;9(2). Epub 2019 Feb 1.

Department of Neurology, Parkinson's Disease and Movement Disorders Section, Institute of Neuroscience of Buenos Aires (INEBA). Guardia Vieja 4435, Buenos Aires C1192AAW, Argentina.

In the last years, lysosomal storage diseases appear as a bridge of knowledge between rare genetic inborn metabolic disorders and neurodegenerative diseases such as Parkinson's disease (PD) or frontotemporal dementia. Epidemiological studies helped promote research in the field that continues to improve our understanding of the link between mutations in the glucocerebrosidase (GBA) gene and PD. We conducted a review of this link, highlighting the association in GBA mutation carriers and in Gaucher disease type 1 patients (GD type 1). Read More

J Inherit Metab Dis 2018 Dec 27. Epub 2018 Dec 27.

Gene Transfer Technology Group, Institute for Women's Health, University College London, London, UK.

Mol Genet Genomic Med 2019 Feb 3:e561. Epub 2019 Feb 3.

Department of Echocardiography, Zhongshan Hospital, Shanghai Institute of Cardiovascular Disease, Shanghai Institute of Medical Imaging, Fudan University, Shanghai, China.

Background: Danon disease is an X-linked dominant hereditary condition caused by mutations in the gene encoding lysosomal-associated membrane protein 2 (LAMP2), leading to failure of lysosome binding to autophagosomes, accumulation of glycogen in the heart, and abnormal cardiac function.

Methods: We describe identification of a mutation in LAMP2, c.741+1G>T, in a family with Danon disease by whole exome sequencing. Read More

Yakugaku Zasshi 2019 ;139(2):143-155

Department of Organic Biomaterials, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University (TMDU).

Recently, the application of β-cyclodextrins (β-CDs) as therapeutic agents has received considerable attention. β-CDs have been reported to have therapeutic effects on various diseases, such as Niemann-Pick type C (NPC) disease, a family of lysosomal storage disorders characterized by the lysosomal accumulation of cholesterol. To further improve the therapeutic efficacy of β-CDs, the use of β-CD-threaded polyrotaxanes (PRXs) has been proposed as a carrier of β-CDs for NPC disease. Read More

Metab Brain Dis 2019 Feb 2. Epub 2019 Feb 2.

Department of Pediatrics, Metabolism Unit, Gazi University, Ankara, Turkey.

Gangliosidoses (GM1 and GM2 gangliosidosis) are rare, autosomal recessive progressive neurodegenerative lysosomal storage disorders caused by defects in the degradation of glycosphingolipids. We aimed to investigate clinical, biochemical and molecular genetic spectrum of Turkish patients with infantile gangliosidoses and examined the potential role of serum aspartate transaminase levels as a biomarker. We confirmed the diagnosis of GM1 and GM2 gangliosidosis based on clinical findings with specific enzyme and/or molecular analyses. Read More

Skeletal Radiol 2019 Feb 2. Epub 2019 Feb 2.

Unidade de Genética, Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP), São Paulo, Brazil.

Objective: The present study aims to provide orientation for clinicians and radiologists to recognize the most prevalent findings leading to diagnosis in mucolipidosis from a description of the natural history of five Brazilian cases.

Materials And Methods: We conducted an observational and retrospective study of five patients with clinical and radiological diagnosis of mucolipidosis. Clinical evaluation consisted of information obtained from records and including physical, neurologic, and dysmorphic evaluations. Read More

J Biol Chem 2019 Feb;294(5):1706-1709

From the Department of Biochemistry, Stanford University School of Medicine, Stanford, California 94305-5307

Low-density lipoprotein particles are taken up by cells and delivered to the lysosome where their cholesterol esters are cleaved off by acid lipase. The released, free cholesterol is then exported from lysosomes for cellular needs or storage. This article summarizes recent advances in our understanding of the molecular basis of cholesterol export from lysosomes. Read More

J Lipid Res 2019 Feb 1. Epub 2019 Feb 1.

University of Geneva, Switzerland;

In specialized cell types, lysosome-related organelles support regulated secretory pathways, while in non-specialized cells, lysosomes can undergo fusion with the plasma membrane in response to a transient rise in cytosolic calcium. Recent evidence also indicates that lysosome secretion can be controlled transcriptionally and promote clearance in lysosome storage diseases. In addition, evidence is also accumulating that low concentrations of cyclodextrins reduce the cholesterol storage phenotype in cells and animals with the cholesterol storage disease Niemann-Pick type C, via an unknown mechanism. Read More

World J Clin Cases 2019 Jan;7(2):203-208

Department of Biotechnology and Genetic Engineering, Philadelphia University, Amman 11118, Jordan.

Background: Late infantile ceroid lipofuscinosis is a rare neurodegenerative disorder that appears between the ages of 2 and 4 years and is difficult to diagnose. In this report we present two sisters with this condition, and the clinical course consisted of delayed developmental skills initially and later regression of previously acquired skills. The cases were initially considered as childhood disintegrative disorder (CDD); however, when whole exome sequencing (WES) genetic testing was done, they proved to be variant late infantile ceroid lipofuscinosis. Read More

J Neurochem 2019 Jan 30. Epub 2019 Jan 30.

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198.

Lysosomes were first described by Christian De Duve in the 1950s (De Duve et al. 1955) and recognized for their role in substrate degradation and recycling. More recently, the lysosome has been identified as a key metabolic hub, influencing processes as diverse as nutrient sensing, secretion, gene regulation, plasma membrane repair, ion homeostasis, immune responses, and cholesterol transport (Bajaj et al. Read More

J Inherit Metab Dis 2018 Dec 27. Epub 2018 Dec 27.

Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany.

Galactosialidosis (GS; OMIM #256540) is a rare multisystemic inborn glycoprotein storage disease caused by biallelic mutations in the cathepsin A gene resulting in combined deficiency of the lysosomal enzymes β-galactosidase and α-neuraminidase. The precise understanding of the natural course of the disease is limited. Development of enzyme replacement therapy is at the preclinical stage. Read More

Eur J Nucl Med Mol Imaging 2019 Jan 28. Epub 2019 Jan 28.

The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia.

Purpose: Niemann-Pick type C (NPC) is a cholesterol storage disease characterized by disruption in the endosomal-lysosomal transport system that leads to the accumulation of cholesterol and glycolipids in lysosomes. Developmental cognitive delay and progressive motor and cognitive impairment are characteristic of the disease. Tau accumulation has been reported in some NPC patients. Read More

J Mol Biol 2019 Jan 25. Epub 2019 Jan 25.

Department of Neurology, University of California, San Francisco, CA 94143, USA. Electronic address:

Single-copy loss-of-function mutations in the progranulin gene (PGRN) underlie the neurodegenerative disease frontotemporal lobar degeneration, while homozygous loss-of-function of PGRN results in the lysosomal storage disorder neuronal ceroid lipofuscinosis. Despite evidence that normal PGRN levels are critical for neuronal health, the function of this protein is not yet understood. Here, we show that PGRN stimulates the in vitro maturation of the lysosomal aspartyl protease cathepsin D (CTSD). Read More

Mol Genet Metab 2019 Jan 22. Epub 2019 Jan 22.

Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address:

Introduction: Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene. Patients with nephropathic cystinosis suffer not only from renal disease but have also other systemic complications like myopathy and swallowing dysfunction. Dysphagia for solid food is mentioned in patients with cystinosis, but in clinical practice swallowing investigations are only performed when the patient has complaints. Read More

J Inherit Metab Dis 2019 Jan 25. Epub 2019 Jan 25.

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

Objective: Lysosomal acid lipase deficiency (LAL-D) is a multi-organ autosomal recessive disease caused by mutations in LIPA.

Study Design: We reviewed data from 681 samples (white blood cells (WBC) n=625, fibroblasts =30, liver =4, amniocytes =13, chorionic villus =9) received for analysis of lysosomal acid lipase (LAL) activity over a 15-year period. LIPA sequencing was performed in 49 patients with reduced (n=26) or deficient (n=23) LAL activity. Read More

J Lipid Res 2019 Jan 25. Epub 2019 Jan 25.

National Institute of Diabetes and Digestive and Kidney Diseases/NIH, United States

The sphingolipid (SL) metabolic pathway generates structurally diverse lipids that have roles as membrane constituents and as bioactive signaling molecules. The influence of the SL metabolic pathway in biology is pervasive; it exists in all mammalian cells and has roles in many cellular and physiological pathways. Human genetic diseases have long been recognized to be caused by mutations in the pathway, but until recently these mutational defects were only known to affect lysosomal SL degradation. Read More

Cardiol Young 2019 Jan 25:1-3. Epub 2019 Jan 25.

2Pediatric Cardiology, Van Training and Research Hospital,University of Health Sciences,Van,Turkey.

Infantile-onset Pompe disease is a lysosomal storage disorder characterised with hypertrophic cardiomyopathy, respiratory insufficiency, and hypotonia. Dilated cardiomyopathy is an extremely rare and curable complication of nutritional hypocalcaemic rickets. A 3-month-old female infant was referred to our paediatric ICU with a 4-day history of fatigue, tachypnoea, tachycardia, hypoxia, and respiratory failure. Read More

Cardiovasc Ultrasound 2019 Jan 23;17(1). Epub 2019 Jan 23.

University of Molise, Health Sciences Department-Campobasso, Campobasso, IT, Italy.

The Anderson-Fabry disease (AFD, or simply Fabry Disease, FD; MIM #301500) is a rare X-linked lysosomal storage disorder (Xq22.1) characterized by progressive renal failure, leading to morbidity through cardio- and cerebro-vascular involvement. Despite the classic phenotype, only cardiac involvement (cardiac variant of AFD; MIM 301500) is frequent in about 40% of male and 28% of female AFD patients, as reported by the Fabry Registry ( https://www. Read More

J Inherit Metab Dis 2019 Jan 22. Epub 2019 Jan 22.

Departments of Neurosciences and Pediatrics, UC San Diego School of Medicine, and Rady Children's Hospital, San Diego, California.

Previous studies have shown that individuals with cystinosis may exhibit difficulty with visuospatial tasks. Global and local (hierarchical) processing are specific types of visuospatial tasks mediated by the right and left parietal lobes respectively. The study objective was to determine whether individuals with cystinosis and carriers of the cystinosin gene mutation show deficits in global and/or local processing. Read More

Int J Mol Sci 2019 Jan 21;20(2). Epub 2019 Jan 21.

Department of Metabolic Biochemistry, Rouen University Hospital, 76000 Rouen, France.

Metabolic phenotyping is poised as a powerful and promising tool for biomarker discovery in inherited metabolic diseases. However, few studies applied this approach to mcopolysaccharidoses (MPS). Thus, this innovative functional approach may unveil comprehensive impairments in MPS biology. Read More

Orphanet J Rare Dis 2019 Jan 21;14(1):19. Epub 2019 Jan 21.

Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, SD, USA.

Background: CLN6-Batten disease is a rare neurodevelopmental disorder characterized pathologically by the accumulation of lysosomal storage material, glial activation and neurodegeneration, and phenotypically by loss of vision, motor coordination, and cognitive ability, with premature death occurring in the second decade of life. In this study, we investigate whether sex differences in a mouse model of CLN6-Batten disease impact disease onset and progression.

Results: A number of noteworthy differences were observed including elevated accumulation of mitochondrial ATP synthase subunit C in the thalamus and cortex of female Cln6 mutant mice at 2 months of age. Read More

Spine Deform 2019 Mar;7(2):298-303

Servicio de Patología Espinal, Hospital de Pediatría Prof. Dr. Juan P. Garrahan, CABA, Buenos Aires, Argentina.

Study Design: Descriptive retrospective cohort of 52 pediatric patients with mucopolysaccharidosis (MPS) and spinal cord disease and surgical outcomes in a reference hospital.

Objectives: To describe clinical manifestations and surgical management and outcomes of spinal lesions.

Methods: All medical records of 52 patients with mucopolysaccharidosis (I, II, III, IV, and VI) diagnosed between 1992 and 2011 were identified and followed at a single spine center of a pediatric hospital. Read More

Med Clin (Barc) 2019 Jan 15. Epub 2019 Jan 15.

Nephrology Department, Fundación Puigvert, RedInRen, IIB Sant Pau, University Autónoma, Barcelona, Spain. Electronic address:

Introduction And Objective: Fabry disease (FD) is an X-linked lysosomal storage disorder due to a deficiency of the α-galactosidase A enzyme. Although women were historically considered only carriers, many studies have contradicted this fact. The main aim of this work was to set the first Spanish study out of the on-going registries on health status and management of women diagnosed with FD who were not receiving enzyme replacement therapy (ERT). Read More

Hum Mol Genet 2019 Jan 18. Epub 2019 Jan 18.

Institute of Biochemistry and Molecular Biology, Rheinische Friedrich-Wilhelms University, D-53115 Bonn, Germany.

Protein-engineering is a means to optimize protein therapeutics developed for the treatment of so far incurable diseases including cancers and genetic disorders. Here we report on an engineering approach in which we successfully increased the catalytic rate constant of an enzyme that is presently evaluated in enzyme replacement therapies (ERT) of a lysosomal storage disease (LSD). Although ERT is a treatment option for many LSDs, outcomes are lagging far behind expectations for most of them. Read More