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Leading the Fight to treat and cure
Tay-Sachs, Canavan, Sandhoff, GM1 and related diseases

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Overview

The leukodystrophies are a group of over 50 rare genetic disorders that affect the central nervous system by disrupting the growth or maintenance of the myelin sheath that insulates nerve cells. Myelin is commonly referred to as the brain's white matter.  Myelin covers nerve cells and ensures the clear transmission of nerve impulses from one part of the body to another. These disorders are progressive, meaning that they tend to get worse throughout the life of the patient.

The word leukodystrophy comes from the Greek words leuko (meaning white), trophy (meaning growth), and dys (meaning ill). If you put these words together, the word leukodystrophy describes a set of diseases that affect the growth or maintenance of the white matter (myelin).

Leukodystrophies differ from multiple sclerosis (MS) in that leukodystrophies are caused by a defect in the genes involved with growth or maintenance of the myelin while MS is believed to be caused by an attack on the myelin by the body's own immune system.

Frequently Asked Questions

Which NTSAD diseases are leukodystrophies?

Canavan and Pelizaeus-Merzbacher are examples of leukodystrophies

What are leukodystrophies?

The leukodystrophies are a group of over 50 rare genetic disorders that affect the central nervous system by disrupting the growth or maintenance of the myelin sheath that insulates nerve cells. Myelin is commonly referred to as the brain's white matter. Myelin covers nerve cells and ensures the clear transmission of nerve impulses from one part of the body to another. These disorders are progressive, meaning that they tend to get worse throughout the life of the patient.

The word leukodystrophy comes from the Greek words leuko (meaning white), trophy (meaning growth), and dys (meaning ill). If you put these words together, the word leukodystrophy describes a set of diseases that affect the growth or maintenance of the white matter (myelin).

Leukodystrophies differ from multiple sclerosis (MS) in that leukodystrophies are caused by a defect in the genes involved with growth or maintenance of the myelin while MS is believed to be caused by an attack on the myelin by the body's own immune system.

 

How does a gene defect cause Canavan Disease?

All of our genes code for specific proteins, which have specific roles in our bodies. In Canavan disease, a defect in the ASPA gene causes an absence of a vital enzyme called aspartoacylase (ASPA.) An enzyme is a type of protein. The job of the ASPA enzyme is to break down N-acetylaspartate acid (NAA). When NAA builds up in the brain it leads to the symptoms of Canavan Disease.

It is sometimes helpful to think of the substrate and the enzyme as a lock and a key. The substrate is the lock, and the enzyme is the key. If the key is made incorrectly, it is not going to fit into the lock. An enzyme is a type of protein. In order for any protein to function correctly, it must contain the correct parts (which are called amino acids) and also be folded correctly.

The enzyme is made incorrectly if the gene that codes for the enzyme contains a spelling error, which is called a mutation. Mutations in the gene can cause the enzyme to contain incorrect parts, or cause it to be folded incorrectly. Sometimes the mutations in the gene cause the enzyme to not be made at all. In infantile Canavan disease, no enzyme is made. In juvenile/milder forms of Canavan disease, some enzyme is made, so there is less build up of NAA in the brain.

How does a gene defect cause Pelizaeus-Merzbacher?

All of our genes code for specific proteins, which have specific roles in our bodies. The PLP1 gene provides the code to build proteolipid protein 1, and a similar protein called DM20. These are the main proteins which are found in myelin. If the PLP1 gene contains a mutation, these proteins will not be made. If these proteins are not made then the myelin sheath cannot be formed correctly. This leads to the symptoms of Pelizaeus-Merzbacher disease.

What techniques can be used to treat Canavan Disease?

The answer to this question can be found on Technology Approaches.

Also, check out the latest Canavan Disease research.



 

If this table width does not fit on your device, you may download the .pdf version of pdf Chart of Allied Diseases (28 KB) .

A. LYSOSOMAL STORAGE DISORDERS

1) Disorders of lipid and sphingolipid degradation

Disease
Enzyme Defect
OMIM#
Inheritance Pattern
Age of Onset
Cognitive Impairment
Links
GM1 Gangliosidosis b-Galactosidase-1
AR
variable progressive psychomotor deterioration  
Tay-Sachs Disease b-Hexosaminidase A
AR
variable progressive psychomotor deterioration  
Sandhoff Disease b-Hexosaminidases A and B
AR
variable progressive psychomotor deterioration  
GM2 Gangliodisosis, AB variant GM2 Activator Protein
AR
infancy progressive psychomotor deterioration  
Fabry Disease 8-Galactosidase A adolesence - adulthood normal intelligence www.fabry.org
Gaucher Disease, Type 1 Glucocerebrosidase
AR
variable normal intelligence www.gaucherdisease.org, www.gaucherdisease.org.uk
Gaucher Disease, Type II Glucocerebrosidase
AR
infancy severe www.gaucherdisease.org, www.gaucherdisease.org.uk
Gaucher Disease, Type III Glucocerebrosidase
AR
childhood mild www.gaucherdisease.org, www.gaucherdisease.org.uk
Metachromatic Leukodystrophy Arylsulfatase A
AR
infancy to adulthood progressive psychomotor deterioration www.ulf.org,
www.MLDFoundation.org
Krabbe Disease Galactosylceramidase
AR
infancy to adulthood progressive psychomotor deterioration www.huntershope.org
Niemann-Pick, Type A Sphingomyelinase
AR
infancy progressive psychomotor deterioration www.nnpdf.org
Niemann-Pick, Type B Sphingomyelinase
AR
infancy - childhood none to mild www.nnpdf.org
Niemann-Pick, Type C1, Type C2 NPC1, HE1 protein (Cholesterol Trafficking Defect)
AR
variable progressive psychomotor deterioration www.parseghian.org
Farber Disease Acid Ceramidase
AR
infancy variable  
Wolman Disease
(Chol.Esther Storage disease)
Lysosomal Acid Lipase
AR
neonatal progressive psychomotor deterioration  
 

2. Disorders of mucopolysaccharide degradation

Disease
Enzyme Defect
OMIM#
Inheritance Pattern
Age of Onset
Cognitive Impairment
Links
Hurler Syndrome (MPSI) L-Iduronidase
AR
infancy severe mental retardation www.mpssociety.org
Scheie Syndrome (MPS IS) L-Iduronidase
AR
childhood normal intelligence www.mpssociety.org
Hurler-Scheie (MPS IH/S) L-Iduronidase
AR
childhood normal intelligence www.mpssociety.org
Hunter Syndrome (MPS II) Iduronate Sulfatase
X-linked
infancy - childhood variable www.mpssociety.org
Sanfilippo A (MPS IIIA) Heparan N--Sulfatase
AR
infancy - childhood progressive psychomotor deterioration www.mpssociety.org
Sanfillippo B (MPS IIIB) N-Acetylglucosaminidase
AR
infancy - childhood progressive psychomotor deterioration www.mpssociety.org
Sanfillippo C (MPS IIIC) Acetyl-CoA-Glucosaminidase
AR
infancy - childhood progressive psychomotor deterioration www.mpssociety.org
Sanfillipo D (MPS IIID) Acetyltransferase
AR
infancy - childhood progressive psychomotor deterioration www.mpssociety.org
Morquio A (MPS IVA) Acetylglucosamine-6-Sulfatase
AR
infancy - childhood normal intelligence www.mpssociety.org,
www.Morquio.com
Morquio B (MPS IVB) Galactosamine-6--Sulfatase
AR
variable normal intelligence

www.mpssociety.org,
www.Morquio.com

Maroteaux-Lamy (MPS VI) Arylsulfatase B
AR
infancy - childhood normal intelligence www.mpssociety.org
Sly Syndrome (MPS VII) Glucuronidase
AR
variable variable www.mpssociety.org
 

3. Disorders of glycoprotein degradation

Disease
Enzyme Defect
OMIM#
Inheritance Pattern
Age of Onset
Cognitive Impairment
Links
Alpha Mannosidosis mannosidase
AR
infancy - adolesence mild to severe mental retardation www.mannosidosis.org
Beta Mannosidosis mannosidase
AR
childhood - adulthood mental retardation www.mannosidosis.org
Fucosidosis l-fucosidase
AR
infancy - adolesence mental retardation www.mannosidosis.org
Asparylglucosaminuria Aspartylglycosaminidase
AR
childhood mental retardation www.mannosidosis.org
Mucolipidosis I (Sialidosis) Neuraminidase
AR
adolesence none (type I) mental retardation (type II) www.mannosidosis.org
Galactosialidosis Lysosomal protective protein
AR
infancy - adulthood variable www.mannosidosis.org
Schindler Disease Lysosomal 8-N-acetylgalactosaminidase
AR
infancy progressive psychomotor deterioration www.mannosidosis.org
Schindler Disease Type II/Kanzaki Disease Lysosomal 8-N-acetylgalactosaminidase
AR
adulthood mild intellectual impairment www.mannosidosis.org
 

4. Other lysosomal storage disorders

Disease
Enzyme Defect
OMIM#
Inheritance Pattern
Age of Onset
Cognitive Impairment
Links
Santavuori-Haltia Disease (Infantile Neuronal Ceroid Lipofuscinosis Type 1) Palmitoyl-protein thioesterase
AR
infancy progressive psychomotor deterioration www.bdsra.org
Jansky-Bielschowsky Disease (Late Infantile Neuronal Ceroid Lipofuscinosis Type 2) at least 4 subtypes
AR
late infancy progressive psychomotor deterioration www.bdsra.org
Batten Disease (Juvenile Neuronal Ceroid Lipofuscinosis Type 3) Lysosomal membrane protein
AR
childhood slow intellect loss/psychosis/variable www.bdsra.org
Kufs Disease (Neuronal Ceroid Lipofuscinosis Type 4) Unknown
AR
adulthood dementia/psychosis www.bdsra.org
Von Gierke Disease (Glycogen storage disease type Ia) Glucose-6-phosphatase
AR
infancy normal intelligence www.agsdus.org
Glycogen storage disease type Ib Glucose-6-phosphate translocase
AR
infancy normal intelligence www.agsdus.org
Pompe Disease (Glycogen Storage Disease Type II) Acid maltase
AR
infancy - adulthood normal intelligence www.pompe.com,
www.amda-pompe.org
Forbes or Cori Disease (Glycogen storage disease type III) Debrancher enzyme amylo-1,6 glucosidase
AR
early childhood normal intelligence www.agsdus.org
Mucolipidosis II (I-Cell Disease) N-acetylglucosamine-1- phosphotransferase
AR
infancy severe psychomotor retardation/developmental delay/mental retardation www.mpssociety.org
Mucolipidosis III (Pseudo-Hurler Polydystrophy) N-acetylglucosamine-1- phosphotransferase
AR
childhood mild to moderate mental retardation/learning disabilities/variable www.mpssociety.org
Mucolipdosis IV (Sialolipidosis) Ganglioside sialidase (neuraminidase)
AR
infancy psychomotor retardation www.ml4.org
Cystinosis (adult nonnephropathic type) Lysosomal cystine transport protein
AR
adulthood normal intelligence www.cystinosisfoundation.org
Cystinosis (infantile nephropathic type) Lysosomal cystine transport protein
AR
infancy normal intelligence www.cystinosisfoundation.org
Cystinosis (juvenile or adolescent nephropathic ) Lysosomal cystine transport protein
AR
adolescence normal intelligence www.cystinosisfoundation.org
Salla Disease/Infantile Sialic acid storage disorder Sialic acid transport protein
AR
infancy - adulthood psychomotor retardation/mental retardation  
Saposin Deficiencies Saposins A, B, C or D
AR
infancy - adulthood neurological deterioration, variable  
 

B. LEUKODYSTROPHY

Disease
Enzyme Defect
OMIM#
Inheritance Pattern
Age of Onset
Cognitive Impairment
Links
Abetalipoproteinemia Microsomal triglyceride transfer protein/apolipoprotein B
AR
infancy - adulthood normal intelligence www.ntsad.org
Adrenoleukodystrophy Peroxisomal membrane transfer protein
X-Linked
childhood and adolescence progressive psychomotor deterioration www.ulf.org, www.myelin.org
Neonatal Adrenoleukodystrophy Peroxins
AR
neonatal severe mental retardation www.ulf.org
Canavan Disease Aspartoacylase
AR
infancy progressive psychomotor deterioration www.canavanfoundation.org, www.ntsad.org
Cerebrotendinous Xanthromatosis Sterol-27-hydroxlase
AR
childhood some have mental retardation while others retain normal intelligence www.ulf.org
Pelizaeus Merzbacher Disease Proteolipid protein
X-linked
infancy perhaps progressive cognitive impairment/dementia but need more neurologic findings www.pmdfoundation.org
Tangier Disease ABC1 transporter
AR
variable normal intelligence www.ntsad.org
Refum Disease, infantile Peroxisome membrane protein 3 or Peroxisome biogenesis factor 1
AR
infancy mental retardation and developmental delay www.ntsad.org
Refum Disease, classic Phytanic acid oxidase
AR
childhood - adulthood normal intelligence www.ntsad.org
             
             
Yes* = if affected family member is found. Note: Reccurance risk after one affected child for all listed diseases = 25% for each pregnancy.
This table reflects information current at the time of printing. Reproductive and/or therapeutic decisions should not be made on the information provided
without first consulting a geneticist or genetic counselor for any updated information.

Autosomal Recessive Inheritance

Tay-Sachs disease, GM-1 and several other allied diseases are autosomal recessive. For recessive conditions, both parents must be carriers for a child to be at risk of inheriting the disease. A carrier has one working copy and one non-working copy of a given gene pair. Males and females are affected equally and carriers are not expected to have adverse health effects.

                                                                            

            

 

         

 

X-linked Inheritance

            



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