lysosomal storage disease

The lysosomal storage diseases are generally classified by the nature of the primary stored material involved, and can be broadly broken into the following: (ICD-10 codes are provided where available){{cn|date=October 2024}}

• (E75) Lipid storage disorders
• Gangliosidoses (including Tay–Sachs disease (E75.0-E75.1) - they are a subtype of sphingolipidoses
• Sphingolipidoses that are not gangliosidoses, including Gaucher's and Niemann–Pick diseases (E75.2-E75.3)
• Leukodystrophies
• (E76.0) Mucopolysaccharidoses, including Hunter syndrome and Hurler disease
• (E77) Glycoprotein storage disorders
• (E77.0-E77.1, E75.11) Mucolipidoses; Mucolipidosis IV is a gangliosidosis

Also, glycogen storage disease type II (Pompe disease) is a defect in lysosomal metabolism as well,[http://emedicine.medscape.com/article/1182830-overview eMedicine Specialties > Neurology > Pediatric Neurology > Lysosomal Storage Disease] Author: Noah S Scheinfeld, MD, JD, FAAD. Coauthor(s): Rowena Emilia Tabamo, MD; Brian Klein, MD. Updated: Sep 25, 2008 although it is otherwise classified into E74.0 in ICD-10. Cystinosis is an lysosomal storage disease characterized by the abnormal accumulation of the amino acid cystine.{{cn|date=October 2024}}

Alternatively to the protein targets, lysosomal storage diseases may be classified by the type of protein that is deficient and is causing buildup.

Lysosomal storage diseases include:

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Sphingolipidoses

• Ceramidase
• Farber disease
• Krabbe disease
• Infantile onset
• Late onset
• Galactosialidosis
• Gangliosides: gangliosidoses
• Alpha-galactosidase
• Fabry disease (alpha-galactosidase A)
• Schindler disease (alpha-galactosidase B)
• Beta-galactosidase / GM1 gangliosidosis
• Infantile
• Juvenile
• Adult / chronic
• GM2 gangliosidosis
• AB variant
• Activator deficiency
• Sandhoff disease
• Infantile
• Juvenile
• Adult onset
• Tay–Sachs
• Juvenile hexosaminidase A deficiency
• Chronic hexosaminidase A deficiency
• Glucocerebroside
• Gaucher disease
• Type I
• Type II
• Type III
• Sphingomyelinase
• Lysosomal acid lipase deficiency
• Early onset
• Late onset
• Niemann–Pick disease
• Type A
• Type B
• Sulfatidosis
• Metachromatic leukodystrophy
• Saposin B deficiency
• Multiple sulfatase deficiency

Mucopolysaccharidoses

• Type I
• MPS I Hurler syndrome
• MPS I S Scheie syndrome
• MPS I H-S Hurler–Scheie syndrome
• Type II (Hunter syndrome)
• Type III (Sanfilippo syndrome)
• MPS III A (Type A)
• MPS III B (Type B)
• MPS III C (Type C)
• MPS III D (Type D)
• Type IV (Morquio)
• MPS IVA (Type A)
• MPS IVB (Type B)
• Type VI (Maroteaux–Lamy syndrome)
• Type VII (Sly syndrome)
• Type IX (hyaluronidase deficiency)

Mucolipidosis

• Type I (sialidosis)
• Type II (I-cell disease)
• Type III (pseudo-Hurler polydystrophy / phosphotransferase deficiency)
• Type IV (mucolipidin 1 deficiency)

Lipidoses

• Niemann–Pick disease
• type C
• Type D
• Neuronal ceroid lipofuscinoses
• Type 1 Santavuori–Haltia disease / infantile NCL (CLN1 PPT1)
• Type 2 Jansky–Bielschowsky disease / late infantile NCL (CLN2/LINCL TPP1)
• Type 3 Batten–Spielmeyer–Vogt disease / juvenile NCL (CLN3)
• Type 4 Kufs disease / adult NCL (CLN4)
• Type 5 Finnish Variant / late infantile (CLN5)
• Type 6 Late infantile variant (CLN6)
• Type 7 CLN7
• Type 8 Northern epilepsy (CLN8)
• Type 8 Turkish late infantile (CLN8)
• Type 9 German/Serbian late infantile (unknown)
• Type 10 Congenital cathepsin D deficiency (CTSD)
• Wolman disease

Oligosaccharide

• Alpha-mannosidosis
• Beta-mannosidosis
• Aspartylglucosaminuria
• Fucosidosis

Lysosomal transport diseases

• Cystinosis
• Pycnodysostosis
• Salla disease / sialic acid storage disease
• Infantile free sialic acid storage disease

Glycogen storage diseases

• Type II Pompe disease
• Type IIb Danon disease{{Cite web |title=Danon disease |url=https://ghr.nlm.nih.gov/condition/danon-disease#genes}}

Other

• Cholesteryl ester storage disease

Lysosomal disease

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The symptoms of lysosomal storage diseases vary depending on the particular disorder and other variables such as the age of onset, and can be mild to severe. They can include developmental delay, movement disorders, seizures, dementia, deafness, and/or blindness. Some people with lysosomal storage diseases have enlarged livers or spleens, pulmonary and cardiac problems, and bones that grow abnormally.{{Cite journal |last=Navarrete-Martínez |first=Juana Inés |last2=Limón-Rojas |first2=Ana Elena |last3=Gaytán-García |first3=Maria de Jesús |last4=Reyna-Figueroa |first4=Jesús |last5=Wakida-Kusunoki |first5=Guillermo |last6=Delgado-Calvillo |first6=Ma. del Rocío |last7=Cantú-Reyna |first7=Consuelo |last8=Cruz-Camino |first8=Héctor |last9=Cervantes-Barragán |first9=David Eduardo |date=May 2017 |title=Newborn screening for six lysosomal storage disorders in a cohort of Mexican patients: Three-year findings from a screening program in a closed Mexican health system |journal=Molecular Genetics and Metabolism |volume=121 |issue=1 |pages=16–21 |doi=10.1016/j.ymgme.2017.03.001 |pmid=28302345}}

The majority of patients are initially screened by enzyme assay, which is the most efficient method to arrive at a definitive diagnosis. In some families where the disease-causing mutations are known, and in certain genetic isolates, mutation analysis may be performed. In addition, after a diagnosis is made by biochemical means, mutation analysis may be performed for certain disorders.{{cn|date=July 2021}}

No cures for lysosomal storage diseases are known, and treatment is mostly symptomatic, although bone marrow transplantation and enzyme replacement therapy (ERT) have been tried with some success.{{Cite journal |vauthors=Clarke JT, Iwanochko RM |year=2005 |title=Enzyme replacement therapy of Fabry disease |journal=Mol. Neurobiol. |volume=32 |issue=1 |pages=043–050 |doi=10.1385/MN:32:1:043 |pmid=16077182 |s2cid=24240533}}{{Cite journal |vauthors=Bruni S, Loschi L, Incerti C, Gabrielli O, Coppa GV |year=2007 |title=Update on treatment of lysosomal storage diseases |journal=Acta Myol |volume=26 |issue=1 |pages=87–92 |pmc=2949325 |pmid=17915580}} ERT can minimize symptoms and prevent permanent damage to the body.{{Cite news |title=Enzyme Replacement Therapy for Gaucher Disease |url=http://www.gaucherdisease.org/gaucher-diagnosis-treatment/treatment/enzyme-replacement-therapy/ |access-date=2017-06-08 |work=National Gaucher Foundation |language=en-US}} In addition, umbilical cord blood transplantation is being performed at specialized centers for a number of these diseases. In addition, substrate reduction therapy, a method used to decrease the production of storage material, is currently being evaluated for some of these diseases. Furthermore, chaperone therapy, a technique used to stabilize the defective enzymes produced by patients, is being examined for certain of these disorders. The experimental technique of gene therapy may offer cures in the future.{{Cite journal |last=Nagree |first=Murtaza S. |last2=Scalia |first2=Simone |last3=McKillop |first3=William M. |last4=Medin |first4=Jeffrey A. |date=2019-07-03 |title=An update on gene therapy for lysosomal storage disorders |url=https://doi.org/10.1080/14712598.2019.1607837 |journal=Expert Opinion on Biological Therapy |volume=19 |issue=7 |pages=655–670 |doi=10.1080/14712598.2019.1607837 |issn=1471-2598 |pmid=31056978 |s2cid=145822883}}{{Cite journal |vauthors=Ponder KP, Haskins ME |year=2007 |title=Gene therapy for mucopolysaccharidosis |journal=Expert Opin Biol Ther |volume=7 |issue=9 |pages=1333–1345 |doi=10.1517/14712598.7.9.1333 |pmc=3340574 |pmid=17727324}}

Ambroxol has recently been shown to increase activity of the lysosomal enzyme glucocerebrosidase, so it may be a useful therapeutic agent for both Gaucher disease and Parkinson's disease.{{Cite journal |last=McNeill |first=Alisdair |last2=Magalhaes |first2=Joana |last3=Shen |first3=Chengguo |last4=Chau |first4=Kai-Yin |last5=Hughes |first5=Derralyn |last6=Mehta |first6=Atul |last7=Foltynie |first7=Tom |last8=Cooper |first8=J. Mark |last9=Abramov |first9=Andrey Y. |date=2014-05-01 |title=Ambroxol improves lysosomal biochemistry in glucocerebrosidase mutation-linked Parkinson disease cells |journal=Brain |language=en |volume=137 |issue=5 |pages=1481–1495 |doi=10.1093/brain/awu020 |issn=0006-8950 |pmc=3999713 |pmid=24574503}}{{Cite journal |last=Albin |first=Roger L. |last2=Dauer |first2=William T. |date=2014-05-01 |title=Magic shotgun for Parkinson's disease? |journal=Brain |language=en |volume=137 |issue=5 |pages=1274–1275 |doi=10.1093/brain/awu076 |issn=0006-8950 |pmid=24771397 |doi-access=free}} Ambroxol triggers the secretion of lysosomes from cells by inducing a pH-dependent calcium release from acidic calcium stores.{{Cite journal |last=Fois |first=Giorgio |last2=Hobi |first2=Nina |last3=Felder |first3=Edward |last4=Ziegler |first4=Andreas |last5=Miklavc |first5=Pika |last6=Walther |first6=Paul |last7=Radermacher |first7=Peter |last8=Haller |first8=Thomas |last9=Dietl |first9=Paul |year=2015 |title=A new role for an old drug: Ambroxol triggers lysosomal exocytosis via pH-dependent Ca2+ release from acidic Ca2+ stores |journal=Cell Calcium |volume=58 |issue=6 |pages=628–637 |doi=10.1016/j.ceca.2015.10.002 |pmid=26560688}} Hence, relieving the cell from accumulating degradation products is a proposed mechanism by which this drug may help.{{cn|date=July 2021}}

Tay–Sachs disease was the first of these disorders to be described, in 1881, followed by Gaucher disease in 1882. In the late 1950s and early 1960s, de Duve and colleagues, using cell fractionation techniques, cytological studies, and biochemical analyses, identified and characterized the lysosome as a cellular organelle responsible for intracellular digestion and recycling of macromolecules. This was the scientific breakthrough that would lead to the understanding of the physiological basis of the lysosomal storage diseases. Pompe disease was the first disease to be identified as an lysosomal storage disease in 1963, with L. Hers reporting the cause as a deficiency of α-glucosidase. Hers also suggested that other diseases, such as the mucopolysaccharidosis, might be due to enzyme deficiencies.{{cn|date=July 2021}}

• Mannosidosis
• Molecular chaperone therapy

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| ICD10 = {{ICD10|E|75||e|70}}-{{ICD10|E|77||e|70}}

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{{Lipid storage disorders}}

{{Mucopolysaccharidoses}}

{{Glycoproteinoses}}

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{{DEFAULTSORT:Lysosomal Storage Disease}}

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Category:Inborn errors of metabolism

Category:Neurological disorders in children

Category:Autosomal recessive disorders

Category:X-linked recessive disorders