Mucolipidosis
Encyclopedia
Mucolipidosis is a group of inherited
metabolic disorders that affect the body's ability to carry out the normal turnover of various materials within cell
s.
When originally named, the mucolipidoses derived their name from the similarity in presentation to both mucopolysaccharidoses and sphingolipidoses
. A biochemical understanding of these conditions has changed how they are classified. Although four conditions (I, II, III, and IV) have been labeled as mucolipidoses, type I (sialidosis
) is now classified as a glycoproteinosis
, and type IV (Mucolipidosis type IV
) is now classified as a gangliosidosis
.
The other two types are closely related.
Mucolipidosis types II and III (ML II and ML III) result from a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase, which phosphorylates target carbohydrate residues on N-linked glycoproteins. Without this phosphorylation, the glycoproteins are not destined for lysosomes, and they escape outside the cell.
The mucolipidoses are inherited in an autosomal recessive
manner, that is, they occur only when a child inherits two copies of the defective gene, one from each parent. When both parents carry a defective gene, each of their children faces a one in four chance of developing one of the MLs. At the same time, each child also faces a one in two chance of inheriting only one copy of the defective gene. People who have only one defective gene are known as carriers. These individuals do not develop the disease but they can pass the defective gene on to their own children. Because the defective genes involved in certain forms of ML are known, tests can identify people who are carriers in some instances.
of ML is based on clinical symptoms, a complete medical history, and certain laboratory
tests.
Heredity
Heredity is the passing of traits to offspring . This is the process by which an offspring cell or organism acquires or becomes predisposed to the characteristics of its parent cell or organism. Through heredity, variations exhibited by individuals can accumulate and cause some species to evolve...
metabolic disorders that affect the body's ability to carry out the normal turnover of various materials within cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s.
When originally named, the mucolipidoses derived their name from the similarity in presentation to both mucopolysaccharidoses and sphingolipidoses
Sphingolipidoses
-Accumulated products:* Gangliosides: Gangliosidosis** GM1 gangliosidoses** GM2 gangliosidoses*** Tay-Sachs disease*** Sandhoff disease* Glycolipids** Fabry's disease** Krabbe disease** Metachromatic leukodystrophy*Glucocerebrosides**Gaucher's disease...
. A biochemical understanding of these conditions has changed how they are classified. Although four conditions (I, II, III, and IV) have been labeled as mucolipidoses, type I (sialidosis
Sialidosis
Mucolipidosis type I or sialidosis is an inherited lysosomal storage disease that results from a deficiency of the enzyme sialidase. The lack of this enzyme results in an abnormal accumulation of complex carbohydrates known as mucopolysaccharides, and of fatty substances known as mucolipids...
) is now classified as a glycoproteinosis
Glycoproteinosis
Glycoproteinosis are lysosomal storage diseases affecting glycoproteins, resulting from defects in lysosomal function. The term is sometimes reserved for conditions involving degradation of glycoproteins.-Types:...
, and type IV (Mucolipidosis type IV
Mucolipidosis type IV
Mucolipidosis type IV is an autosomal recessive lysosomal storage disorder. Individuals with the disorder have many symptoms including delayed psychomotor development and various ocular aberrations. The disorder is caused by mutations in the MCOLN1 gene, which encodes a non-selective cation...
) is now classified as a gangliosidosis
Gangliosidosis
Gangliosidosis is a lipid storage disorder 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 equally.-See also:...
.
ML II and III
- For details, see I-cell diseaseI-cell diseaseInclusion-cell disease, also referred to as mucolipidosis II , is part of the lysosomal storage disease family and results from a defective phosphotransferase . This enzyme transfers phosphate to mannose residues on specific proteins, and serves as a marker for them to be targeted to lysosomes...
(type II) and Pseudo-Hurler polydystrophyPseudo-Hurler polydystrophyPseudo-Hurler polydystrophy, also referred to as mucolipidosis III , is a lysosomal storage disease closely related to I-cell disease...
(type III)
The other two types are closely related.
Mucolipidosis types II and III (ML II and ML III) result from a deficiency of the enzyme N-acetylglucosamine-1-phosphotransferase, which phosphorylates target carbohydrate residues on N-linked glycoproteins. Without this phosphorylation, the glycoproteins are not destined for lysosomes, and they escape outside the cell.
Genetics
Recessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
manner, that is, they occur only when a child inherits two copies of the defective gene, one from each parent. When both parents carry a defective gene, each of their children faces a one in four chance of developing one of the MLs. At the same time, each child also faces a one in two chance of inheriting only one copy of the defective gene. People who have only one defective gene are known as carriers. These individuals do not develop the disease but they can pass the defective gene on to their own children. Because the defective genes involved in certain forms of ML are known, tests can identify people who are carriers in some instances.
Diagnosis
The diagnosisDiagnosis
Diagnosis is the identification of the nature and cause of anything. Diagnosis is used in many different disciplines with variations in the use of logics, analytics, and experience to determine the cause and effect relationships...
of ML is based on clinical symptoms, a complete medical history, and certain laboratory
Laboratory
A laboratory is a facility that provides controlled conditions in which scientific research, experiments, and measurement may be performed. The title of laboratory is also used for certain other facilities where the processes or equipment used are similar to those in scientific laboratories...
tests.