Lysosomal Storage Disorders Diagnostic Algorithm, Part 2

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Lysosomal Storage Disorders Diagnostic Algorithm, Part 2 Clinical information: ■ Developmental delay/Cognitive impairment ■ Coarse features/Organomegaly ■ Dysostosis multiplex ■ Neurodegeneration/Behavioral changes ■ Ichthyosis ■ Hearing defects/loss LSDS / Lysosomal Storage Disorders Screen, Random, Urine Testing includes: ■ Mucopolysaccharides (MPS) ■ Oligosaccharides (OLIGO) ■ Ceramide trihexosides (CT) ■ Sulfatides (S) ■ OLIGO: ML II/III profile ■ S: abnormal ■ CT and S: abnormal ■ MPS and S: abnormal ■ CT: abnormal ■ OLIGO: characteristic profile ■ CT, MPS and S: normal/abnormal ■ CT, MPS and OLIGO: normal ■ MPS and OLIGO: normal ■ CT and OLIGO: normal ■ MPS, OLIGO and S: normal ■ CT, MPS and S; normal Mucolipidosis (ML) II/III Metachromatic Prosaposin/ SaposinB Multiple sulfatase deficiency (MSD) Fabry disease leukodystrophy (MLD) Order BOTH of the following: For recommended diagnostic One of the following One of the following ■ ARSAW / Arylsulfatase A, workup, see Fabry Disease suspected: suspected: Order: GNPTZ / GNPTAB Gene, Order 1 of the following: Leukocytes Diagnostic Testing Algorithm ■ Aspartylglucosaminuria ■ NGLY1 deficiency Full Gene Analysis, Varies ■ ARSAW / Arylsulfatase A, Leukocytes ■ I2SW / Iduronate-2-Sulfatase, ■ α-Mannosidosis (Congenital disorder of ■ ARSU / Arylsulfatase A, 24 Hour, Urine Whole Blood ■ β-Mannosidosis glycosylation: CDG-Iv) ■ Pompe disease ■ MOGS-CDG (CDG-IIb) ■ Sandhoff disease ■ Schindler disease If both results are deficient, ■ Sialidosis MSD confirmed If deficient, If normal, possible Saposin ■ Galactosialidosis* MLD confirmed B or alternate diagnosis ■ α-Fucosidosis* ■ Mucolipidosis II/III* Consider: CDGGP / Congenital ■ GM1 gangliosidosis* Disorders of Glycosylation ■ Morquio A & B* Gene Panel, Varies Consider: ARSAZ / ARSA Consider: PSAP sequencing Consider: SUMFZ / Multiple Sulfatase Gene, Full Gene Analysis, Varies Deficiency, Full Gene Analysis, Varies Consider: LSDGP / Lysosomal, Storage Disease Gene Panel, Varies * These conditions may also have elevated MPS © Mayo Foundation for Medical Education and Research (MFMER). All rights reserved. 03/2021.

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An in Vitro Model for Lysosomal Storage Diseases Using Aspartylglucosaminuria Patient Cells
AN IN VITRO MODEL FOR LYSOSOMAL STORAGE DISEASES USING ASPARTYLGLUCOSAMINURIA PATIENT CELLS Master´s Thesis University of Turku MSc Degree Programme in Biomedical Sciences Drug Discovery and Development 4/2020 Maria Kjellman Supervisors Riikka Äänismaa, PhD Senior Scientist Therapy Area Rare Diseases Orion Corporation Orion Pharma Jarkko Venäläinen, PhD Principal Scientist Therapy Area Rare Diseases Orion Corporation Orion Pharma Ullamari Pesonen, PhD Professor of Pharmacology and Drug Development Institute of Biomedicine Faculty of Medicine University of Turku Pharmacology, Drug Development and Therapeutics The originality of this thesis has been verified in accordance with the University of Turku quality assurance system using the Turnitin OriginalityCheck service. ABSTRACT UNIVERSITY OF TURKU Institute of Biomedicine, Faculty of Medicine KJELLMAN, MARIA: An In Vitro Model for Lysosomal Storage Diseases Using Aspartylglucosaminuria Patient Cells Master‘s Thesis, 73 pages MSc Degree Programme in Biomedical Sciences Drug Discovery and Development April 2020 BACKGROUND Lysosomes are acidic organelles responsible for recycling of metabolic byproducts and cellular debris, and there are approximately 60 enzymes within lysosomes responsible for the recycling process. These enzymes can be malfunctional due to genetic mutations, which results in a lysosomal storage disease (LSD). One of these diseases is aspartylglucosaminuria (AGU) caused by an incorrectly folded aspartylglucosaminidase (AGA) enzyme, which results in a buildup of the substrate aspartylglucosamine. This enzymatic deficiency impairs the cellular function in both central nervous system (CNS) and periphery manifesting as an impaired physical and mental development. UNMET MEDICAL NEED Currently, there are no curative or even symptom alleviating treatments available. AIM The aim of this research was to establish a reliable in vitro model of LSD to enable repeatable experiments for drug development purposes.
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