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Lysosomal storage diseases (LSDs; ) are a group of over 70 rare inherited
metabolic disorders A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients A nutrient is a substance Substance may refer to: * Substance (Jainism), a term in Jain ontology to denote the base or owner of at ...
that result from defects in lysosomal function.
Lysosome A lysosome () is a membrane-bound organelle found in many animal Cell (biology), cells. They are spherical Vesicle (biology and chemistry), vesicles that contain Hydrolysis, hydrolytic enzymes that can break down many kinds of biomolecules. A ly ...

Lysosome
s are sacs of enzymes within cells that digest large molecules and pass the fragments on to other parts of the cell for recycling. This process requires several critical enzymes. If one of these enzymes is defective due to a mutation, the large molecules accumulate within the cell, eventually killing it. Lysosomal storage disorders are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the
metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life Life is a characteristic that distinguishes physical entities A bubble of exhaled gas in water In common usage and classical mechanics, a phys ...

metabolism
of
lipid In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanis ...
s,
glycoprotein Glycoproteins are protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , providing and , and from one location to another. Proteins dif ...
s (sugar-containing proteins), or so-called
mucopolysaccharide . For polysaccharide nomenclature see here. R1, R2, R3 may have different values. Image:Hyaluronan.svg, 240px, Hyaluronic acid, Hyaluronan (-4GlcUA''β''1-3GlcNAc''β''1-)n Glycosaminoglycans (GAGs) or mucopolysaccharides are long linear polysac ...
s. Individually, LSDs occur with incidences of less than 1:100,000; however, as a group, the incidence is about 1:5,000 – 1:10,000. Most of these disorders are
autosomal recessive In genetics Genetics is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interact ...

autosomal recessive
ly inherited such as
Niemann–Pick disease, type C Niemann–Pick type C (NPC) is a lysosomal storage disease associated with mutations in NPC1 and NPC2 genes. Niemann–Pick type C affects an estimated 1:150,000 people. Approximately 50% of cases present before 10 years of age, but manifestations m ...
, but a few are
X-linked recessive X-linked recessive inheritance is a mode of inheritance Inheritance is the practice of passing on private property, Title (property), titles, debts, entitlements, Privilege (law), privileges, rights, and Law of obligations, obligations upon th ...

X-linked recessive
ly inherited, such as
Fabry disease Fabry disease, also known as Anderson–Fabry disease, is a rare genetic disease that can affect many parts of the body, including the kidneys, heart, and integumentary system, skin. Fabry disease is one of a group of conditions known as lysosoma ...
and
Hunter syndrome Hunter syndrome, or mucopolysaccharidosis Mucopolysaccharidoses are a group of metabolic disorder A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients such as proteins, fats, and ...
(MPS II). The lysosome is commonly referred to as the cell's recycling center because it processes unwanted material into substances that the cell can use. Lysosomes break down this unwanted matter by
enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...

enzyme
s, highly specialized
protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, for which they received a No ...

protein
s essential for survival. Lysosomal disorders are usually triggered when a particular enzyme exists in too small an amount or is missing altogether. When this happens, substances accumulate in the cell. In other words, when the lysosome does not function normally, excess products destined for breakdown and recycling are stored in the cell. Like other
genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome In the fields of molecular biology Molecular biology is the branch of biology Biology is the natural science that studies life and li ...
s, individuals inherit lysosomal storage diseases from their parents. Although each disorder results from different gene mutations that translate into a deficiency in enzyme activity, they all share a common biochemical characteristic – all lysosomal disorders originate from an abnormal accumulation of substances inside the lysosome. LSDs affect mostly children and they often die at a young age, many within a few months or years of birth.


Classification


Standard classification

The LSDs are generally classified by the nature of the primary stored material involved, and can be broadly broken into the following: (
ICD-10 ICD-10 is the 10th revision of the International Statistical Classification of Diseases and Related Health Problems The International Classification of Diseases (ICD) is a globally used diagnostic Diagnosis is the identification of the nature ...

ICD-10
codes are provided where available) * (E75)
Lipid storage disorder A lipid storage disorder (or lipidosis) is any one of a group of inherited metabolism, metabolic disorders in which harmful amounts of fats or lipids accumulate in some of the body’s cell (biology), cells and tissues. People with these disorder ...
s **
Sphingolipidoses Sphingolipidoses are a class of lipid storage disorders or degenerative storage disorders caused by deficiency of an enzyme that is required for the catabolism of lipids that contain ceramide,Lynn, D. Joanne, Newton, Herbert B. and Rae-Grant, Alex ...

Sphingolipidoses
, including Gaucher's and
Niemann–Pick disease Niemann–Pick disease is a group of severe inherited metabolic disorders A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients A nutrient is a substance Substance may refer to: * Sub ...

Niemann–Pick disease
s (E75.0-E75.1) **
Gangliosidosis Gangliosidosis contains different types of lipid storage disorders caused by the accumulation of lipids known as gangliosides. There are two distinct genetic causes of the disease. Both are autosomal recessive and affect males and females equall ...
(including
Tay–Sachs disease Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease which becomes apparent around three to six months of age, with the baby lo ...
(E75.2) **
Leukodystrophies Leukodystrophies are a group of usually inherited disorders characterized by degeneration Degeneracy, degenerate, or degeneration may refer to: Arts and entertainment * Degenerate (album), ''Degenerate'' (album), a 2010 album by the British ba ...
* (E76.0)
Mucopolysaccharidoses Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunctioning of lysosome, lysosomal enzymes needed to break down molecules called glycosaminoglycans (GAGs). These long chains of sugar carbohydrates occur within ...
, including
Hunter syndrome Hunter syndrome, or mucopolysaccharidosis Mucopolysaccharidoses are a group of metabolic disorder A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients such as proteins, fats, and ...
and
Hurler disease Hurler syndrome, also known as mucopolysaccharidosis Type IH (MPS-IH), Hurler's disease, and formerly gargoyle, gargoylism, is a genetic disorder that results in the buildup of large sugar molecules called glycosaminoglycans (GAGs) in lysosomes. Th ...
* (E77) Glycoprotein storage disorders * (E77.0-E77.1) Mucolipidoses Also,
glycogen storage disease type II Glycogen storage disease type II, also called Pompe disease, is an autosomal recessive metabolic disorder which damages muscle and nerve cells throughout the body. It is caused by an accumulation of glycogen in the lysosome due to deficiency of th ...
(Pompe disease) is a defect in lysosomal metabolism as well, although it is otherwise classified into E74.0 in ICD-10.
Cystinosis Cystinosis is a lysosomal storage disease Lysosomal storage diseases (LSDs; ) are a group of about 50 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest larg ...

Cystinosis
is an LSD characterized by the abnormal accumulation of the amino acid cystine.


By type of defect protein

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


Lysosomal storage disorders

These are LSDs: *
Sphingolipidoses Sphingolipidoses are a class of lipid storage disorders or degenerative storage disorders caused by deficiency of an enzyme that is required for the catabolism of lipids that contain ceramide,Lynn, D. Joanne, Newton, Herbert B. and Rae-Grant, Alex ...

Sphingolipidoses
*
Ceramidase Ceramidase (, ''acylsphingosine deacylase'', ''glycosphingolipid ceramide deacylase'') is an enzyme which cleaves fatty acids from ceramide Ceramide. R represents the alkyl portion of a fatty acid. Ceramides are a family of wax , a typical wax ...
**
Farber disease Farber disease (also known as Farber's lipogranulomatosis, acid ceramidase deficiency, "Lipogranulomatosis", and ''ASAH1''-related disorders) is an extremely rare, progressive, autosomal recessive lysosomal storage disease caused by a deficiency ...
**
Krabbe disease Krabbe disease (KD) (also known as globoid cell leukodystrophy or galactosylceramide lipidosis) is a rare and often fatal lysosomal storage disease that results in progressive neurodegenerative disorder, damage to the nervous system. KD involves s ...
*** Infantile onset *** Late onset *
Galactosialidosis Galactosialidosis, also known as neuraminidase Neuraminidase (Sialidase) enzymes are glycoside hydrolase 1HNY, a glycoside hydrolase Glycoside hydrolases (also called glycosidases or glycosyl hydrolases) catalysis, catalyze the hydrolysis ...
*
Gangliosides A ganglioside is a molecule composed of a glycosphingolipidImage:Sphingosine structure.svg, Sphingosine Glycosphingolipids are a subtype of glycolipids containing the amino alcohol sphingosine. They may be considered as sphingolipids with an atta ...
:
gangliosidoses Gangliosidosis contains different types of lipid storage disorders caused by the accumulation of lipids known as gangliosides. There are two distinct genetic causes of the disease. Both are autosomal recessive and affect males and females equall ...
**
Alpha-galactosidase Alpha-galactosidase (α-GAL, also known as α-GAL A; E.C. 3.2.1.22) is a glycoside hydrolase Glycoside hydrolases (also called glycosidases or glycosyl hydrolases) catalyze that utilizes a low-temperature oxidation catalyst to convert ca ...
***
Fabry disease Fabry disease, also known as Anderson–Fabry disease, is a rare genetic disease that can affect many parts of the body, including the kidneys, heart, and integumentary system, skin. Fabry disease is one of a group of conditions known as lysosoma ...
(alpha-galactosidase A) ***
Schindler disease Schindler disease, also known as Kanzaki disease and alpha-N-acetylgalactosaminidase deficiency is a rare disease found in humans. This lysosomal storage disorder is caused by a deficiency in the enzyme alpha-NAGA (alpha-N-acetylgalactosaminidase ...
(alpha-galactosidase B) **
Beta-galactosidase β-galactosidase, also called lactase, beta-gal or β-gal, is a family of glycoside hydrolase 1HNY, a glycoside hydrolase Glycoside hydrolases (also called glycosidases or glycosyl hydrolases) catalysis, catalyze the hydrolysis Hydrolysis (; ...

Beta-galactosidase
/ GM1 gangliosidosis *** Infantile *** Juvenile *** Adult / chronic ** GM2 gangliosidosis *** AB variant *** Activator deficiency ***
Sandhoff disease Sandhoff disease is a lysosomal genetic, lipid storage disorder caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, ...
**** Infantile **** Juvenile **** Adult onset *** Tay–Sachs **** Juvenile hexosaminidase A deficiency **** Chronic hexosaminidase A deficiency *
Glucocerebroside Glucocerebroside (also called glucosylceramide) is any of the cerebrosides in which the monosaccharide head group is glucose. Clinical significance In Gaucher disease, the enzyme glucocerebrosidase is nonfunctional and cannot break down glucocer ...
**
Gaucher disease Gaucher's disease or Gaucher disease () (GD) is a genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome In the fields of molecular biology Molecular biology is the branch of bi ...
*** Type I *** Type II *** Type III *
Sphingomyelinase Sphingomyelin phosphodiesterase (, also known as neutral sphingomyelinase, sphingomyelinase, or SMase) is a hydrolase Hydrolase is a class of enzyme that commonly perform as biochemical catalysts that use water to break a chemical bond, which t ...
**
Lysosomal acid lipase deficiency Lysosomal acid lipase deficiency (LAL deficiency or LAL-D), is an autosomal recessive In genetics Genetics is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, phys ...
*** Early onset *** Late onset **
Niemann–Pick disease Niemann–Pick disease is a group of severe inherited metabolic disorders A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients A nutrient is a substance Substance may refer to: * Sub ...

Niemann–Pick disease
*** Type A *** Type B * Sulfatidosis **
Metachromatic leukodystrophy Metachromatic leukodystrophy (MLD) is a lysosomal storage disease which is commonly listed in the family of leukodystrophies as well as among the sphingolipidoses as it affects the metabolism of sphingolipids. Leukodystrophies affect the growth ...
*** Saposin B deficiency **
Multiple sulfatase deficiency Multiple sulfatase deficiency (MSD), also known as Austin disease, or mucosulfatidosis, is a very rare autosomal recessive In genetics Genetics is a branch of biology Biology is the natural science that studies life and living org ...
Mucopolysaccharidoses Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunctioning of lysosome, lysosomal enzymes needed to break down molecules called glycosaminoglycans (GAGs). These long chains of sugar carbohydrates occur within ...
* Type I ** MPS I
Hurler syndrome Hurler syndrome, also known as mucopolysaccharidosis Mucopolysaccharidoses are a group of metabolic disorder A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients such as proteins, ...
** MPS I S
Scheie syndrome Scheie syndrome is a disease caused by a deficiency in the enzyme iduronidase, leading to the buildup of glycosaminoglycans (GAGs) in the body. It is the most mild subtype of mucopolysaccharidosis type I; the most severe subtype of this disease i ...
** MPS I H-S
Hurler–Scheie syndrome Hurler–Scheie syndrome is a genetic disorder caused by the buildup of glycosaminoglycans (GAGs) in various organ tissues. It is a cutaneous condition, also characterized by mild Mental Retardation, mental retardation and Cornea, corneal clouding. ...
* Type II (
Hunter syndrome Hunter syndrome, or mucopolysaccharidosis Mucopolysaccharidoses are a group of metabolic disorder A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients such as proteins, fats, and ...
) * Type III (
Sanfilippo syndrome Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is a rare autosomal recessive lysosomal storage disease that primarily affects the Human brain, brain and spinal cord. It is caused by a buildup of large sugar molecule ...
) ** MPS III A (Type A) ** MPS III B (Type B) ** MPS III C (Type C) ** MPS III D (Type D) * Type IV (
Morquio
Morquio
) ** MPS IVA (Type A) ** MPS IVB (Type B) * Type VI ( Maroteaux–Lamy syndrome) * Type VII (
Sly syndrome Sly syndrome, also called mucopolysaccharidosis Mucopolysaccharidoses are a group of metabolic disorder A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients such as proteins, fats ...
) * Type IX ( hyaluronidase deficiency) Mucolipidosis * Type I (
sialidosis Mucolipidosis type I (ML I) is an inherited lysosomal storage disease Lysosomal storage diseases (LSDs; ) are a group of over 70 rare inherited metabolic disorders A metabolic disorder is a disorder that negatively alters the body's processing ...
) * Type II (
I-cell disease Inclusion-cell (I-cell) disease, also referred to as mucolipidosis II (ML II), is part of the lysosomal storage disease family and results from a defective phosphotransferase (an enzyme of the Golgi apparatus). This enzyme transfers phosphate to m ...
) * Type III (pseudo-Hurler polydystrophy /
phosphotransferase Phosphotransferases are a category of enzymes (Enzyme Commission number, EC number 2.7) that catalyze phosphorylation reactions. The general form of the reactions they catalyze is: :A-P + B \rightleftharpoons B-P + A Where ''P'' is a phosphate grou ...
deficiency) * Type IV ( mucolipidin 1 deficiency) Lipidoses *
Niemann–Pick disease Niemann–Pick disease is a group of severe inherited metabolic disorders A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients A nutrient is a substance Substance may refer to: * Sub ...

Niemann–Pick disease
** type C ** Type D *
Neuronal ceroid lipofuscinoses Neuronal ceroid lipofuscinosis is the general name for a family of at least eight genetically separate Neurodegenerative disorder, neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) in ...
** Type 1 Santavuori–Haltia disease / infantile NCL (CLN1
PPT1 Palmitoyl-protein thioesterase 1 (PPT-1), also known as palmitoyl-protein hydrolase 1, is an enzyme that in humans is encoded by the PPT1 gene. Function PPT-1 a member of the palmitoyl protein thioesterase family. PPT-1 is a small glycoprotein ...
) ** Type 2 Jansky–Bielschowsky disease / late infantile NCL (CLN2/LINCL
TPP1 Tripeptidyl-peptidase 1, also known as Lysosomal pepstatin-insensitive protease, is an enzyme that in humans is encoded by the ''TPP1'' gene. TPP1 should not be confused with the TPP1 shelterin protein which protects telomeres and is encoded by th ...
) ** Type 3 Batten–Spielmeyer–Vogt disease / juvenile NCL (
CLN3 Battenin is a protein Proteins are large s and s that comprise one or more long chains of . Proteins perform a vast array of functions within organisms, including , , , providing and , and from one location to another. Proteins differ fro ...
) ** Type 4 Kufs disease / adult NCL ( CLN4) ** Type 5 Finnish Variant / late infantile (
CLN5 Ceroid-lipofuscinosis neuronal protein 5 is a protein that in humans is encoded by the ''CLN5'' gene. The neuronal ceroid lipofuscinoses (CLN or NCL) are a group of autosomal recessive, progressive encephalopathies in children. They are character ...
) ** Type 6 Late infantile variant (
CLN6 Ceroid-lipofuscinosis neuronal protein 6 is a protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir Joh ...
) ** Type 7 CLN7 ** Type 8 Northern epilepsy (
CLN8 Protein CLN8 is a protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, f ...
) ** Type 8 Turkish late infantile (
CLN8 Protein CLN8 is a protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, f ...
) ** Type 9 German/Serbian late infantile (unknown) ** Type 10 Congenital cathepsin D deficiency (
CTSD Cathepsin D is a protein that in humans is encoded by the ''CTSD'' gene. This gene encodes a lysosome, lysosomal aspartyl protease composed of a protein dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor ...
) *
Wolman disease Lysosomal acid lipase deficiency (LAL deficiency or LAL-D), is an autosomal recessive inborn error of metabolism that results in the body not producing enough active Lysosomal lipase, lysosomal acid lipase (LAL) enzyme. This enzyme plays an importa ...
Oligosaccharide An oligosaccharide (/ˌɑlɪgoʊˈsækəˌɹaɪd/; from the Greek ὀλίγος ''olígos'', "a few", and σάκχαρ ''sácchar'', "sugar") is a saccharide is a disaccharide A disaccharide (also called a double sugar or ''biose'') is the sug ...
*
Alpha-mannosidosis Alpha-mannosidosis is a lysosomal storage disorder, first described by Swedish physician Okerman in 1967.''Malm D, Nilssen O (2008). "Alpha-mannosidosis". Orphanet J Rare Dis. 3 (1): 21. Digital object identifier, doi:10.1186/1750-1172-3-21. Pub ...
* Beta-mannosidosis *
Aspartylglucosaminuria Aspartylglucosaminuria (AGU) is an inherited disease that is characterized by a decline in mental functioning, accompanied by an increase in skin, bone and joint issues. The disease is caused by a defect in an enzyme known as aspartylglucosaminida ...
*
Fucosidosis Fucosidosis is a rare lysosomal storage disorder in which the FUCA1 gene experiences mutations that severely reduce or stop the activity of the alpha-L-fucosidase enzyme. The result is a buildup of complex sugars in parts of the body, which leads ...
Lysosomal transport diseases *
Cystinosis Cystinosis is a lysosomal storage disease Lysosomal storage diseases (LSDs; ) are a group of about 50 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes are sacs of enzymes within cells that digest larg ...

Cystinosis
*
Pycnodysostosis Pycnodysostosis (from Greek#REDIRECT Greek Greek may refer to: Greece Anything of, from, or related to Greece Greece ( el, Ελλάδα, , ), officially the Hellenic Republic, is a country located in Southeast Europe. Its population is ap ...
* Salla disease / sialic acid storage disease * Infantile free sialic acid storage disease Glycogen storage diseases * Type II
Pompe disease Glycogen storage disease type II, also called Pompe disease, is an autosomal recessive metabolic disorder which damages muscle and nerve cells throughout the body. It is caused by an accumulation of glycogen in the lysosome due to deficiency of th ...
* Type IIb
Danon disease Danon disease (or glycogen storage disease Type IIb) is a metabolic disorder. Danon disease is an X-linked lysosomal and glycogen storage disorder associated with hypertrophic cardiomyopathy, skeletal muscle weakness, and intellectual disability. I ...
Other *
Cholesteryl ester storage disease Lysosomal acid lipase deficiency (LAL deficiency or LAL-D), is an autosomal recessive inborn error of metabolism that results in the body not producing enough active Lysosomal lipase, lysosomal acid lipase (LAL) enzyme. This enzyme plays an importa ...
Lysosomal disease


Signs and symptoms

The symptoms of LSD 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 An epileptic seizure, formally known as a seizure, is a period of symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower tem ...
,
dementia Dementia manifests as a set of related symptoms, which usually surface when the brain is damaged by injury or disease. The symptoms Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or ...
,
deafness Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss Hearing loss is a partial or total inability to hear Hearing, or auditory perception, is the ability ...
, and/or
blindness Visual impairment, also known as vision impairment or vision loss, is a decreased ability to see to a degree that causes problems not fixable by usual means, such as glasses Glasses, also known as eyeglasses or spectacles, are vision eyew ...
. Some people with LSD have enlarged livers or spleens,
pulmonary The lungs are the primary organs of the respiratory system The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animal ...
and
cardiac The heart is a muscle, muscular Organ (anatomy), organ in most animals, which pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as ...
problems, and bones that grow abnormally.


Diagnosis

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.


Treatment

No cures for lysosomal storage diseases are known, and treatment is mostly symptomatic, although
bone marrow transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cell Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis Ha ...
and
enzyme replacement therapy Enzymes () are protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958 ...
(ERT) have been tried with some success. ERT can minimize symptoms and prevent permanent damage to the body. In addition,
umbilical cord blood Cord blood (umbilical cord blood) is blood that remains in the placenta and in the attached umbilical cord after childbirth. Cord blood is collected because it contains stem cells, which can be used to treat hematopoietic and genetic disorders such ...
transplantation is being performed at specialized centers for a number of these diseases. In addition,
substrate reduction therapy Substrate reduction therapy offers an approach to treatment of certain metabolic disorders, especially glycogen storage diseases and lysosomal storage disorders. In a storage disorder, a critical failure in a metabolic pathway prevents cellular brea ...
, 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 Gene therapy is a medical Medicine is the science Science () is a systematic enterprise that builds and organizes knowledge Knowledge is a familiarity, awareness, or understanding of someone or something, such as facts ( descri ...

gene therapy
may offer cures in the future.
Ambroxol Ambroxol is a drug that breaks up phlegm Phlegm (; , ''phlégma'', "inflammation", "humour Humour (English in the Commonwealth of Nations, Commonwealth English) or humor (American English) is the tendency of experiences to provoke laughter ...

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 Parkinson's disease (PD), or simply Parkinson's, is a chronic condition, long-term neurodegeneration, degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disea ...
. Ambroxol triggers the secretion of
lysosome A lysosome () is a membrane-bound organelle found in many animal Cell (biology), cells. They are spherical Vesicle (biology and chemistry), vesicles that contain Hydrolysis, hydrolytic enzymes that can break down many kinds of biomolecules. A ly ...

lysosome
s from cells by inducing a pH-dependent calcium release from acidic calcium stores. Hence, relieving the cell from accumulating degradation products is a proposed mechanism by which this drug may help.


History

Tay–Sachs disease Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease which becomes apparent around three to six months of age, with the baby lo ...
was the first of these disorders to be described, in 1881, followed by
Gaucher disease Gaucher's disease or Gaucher disease () (GD) is a genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome In the fields of molecular biology Molecular biology is the branch of bi ...
in 1882. In the late 1950s and early 1960s, de Duve and colleagues, using cell fractionation techniques,
cytological Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biolog ...
studies, and biochemical analyses, identified and characterized the lysosome as a cellular organelle responsible for
intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chem ...
digestion and recycling of
macromolecules A macromolecule is a very large molecule A molecule is an electrically Electricity is the set of physical phenomena associated with the presence and motion Image:Leaving Yongsan Station.jpg, 300px, Motion involves a change in ...
. This was the scientific breakthrough that would lead to the understanding of the physiological basis of the LSDs.
Pompe disease Glycogen storage disease type II, also called Pompe disease, is an autosomal recessive metabolic disorder which damages muscle and nerve cells throughout the body. It is caused by an accumulation of glycogen in the lysosome due to deficiency of th ...
was the first disease to be identified as an LSD in 1963, with L. Hers reporting the cause as a deficiency of α-glucosidase. Hers also suggested that other diseases, such as the
mucopolysaccharidosis Mucopolysaccharidoses are a group of metabolic disorder A metabolic disorder is a disorder that negatively alters the body's processing and distribution of macronutrients such as proteins, fats, and carbohydrates. Metabolic disorders can happe ...
, might be due to enzyme deficiencies.


See also

* *
Molecular chaperone therapy A pharmacological chaperone or pharmacoperone is a drug that acts as a chaperone (protein), protein chaperone. That is, it contains small molecules that enter cells and serve as a molecular scaffolding in order to cause otherwise-protein folding, ...


References


External links

{{DEFAULTSORT:Lysosomal Storage Disease * Inborn errors of metabolism Neurological disorders in children Autosomal recessive disorders X-linked recessive disorders