A lipid storage disorder (or lipidosis) is any one of a group of inherited metabolic disorders in which harmful amounts of fats or

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids includ ...

s accumulate in some body cells and tissues. People with these disorders either do not produce enough of one of the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

s needed to metabolize and break down lipids or, they produce enzymes that do not work properly. Over time, the buildup of fats may cause permanent cellular and tissue damage, particularly in the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

, and bone marrow. Inside cells under normal conditions,

lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane pr ...

s convert, or metabolize, lipids and proteins into smaller components to provide energy for the body.

Classification

Disorders that store this

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

material are part of the lysosomal storage diseases family of disorders.

Sphingolipidoses

Many lipid storage disorders can be classified into the subgroup of

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 ...

, as they relate to

sphingolipid Sphingolipids are a class of lipids containing a backbone of sphingoid bases, a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx because o ...

metabolism. Members of this group include Niemann-Pick disease,

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 skin. Fabry disease is one of a group of conditions known as lysosomal storage diseases. T ...

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 damage to the nervous system. KD involves dysfunctional metabolism of ...

Gaucher disease Gaucher's disease or Gaucher disease () (GD) is a genetic disorder in which glucocerebroside (a sphingolipid, also known as glucosylceramide) accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue, anemia, low ...

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 ...

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 ...

, multiple sulfatase deficiency, and

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 ...

. They are generally inherited in an autosomal recessive fashion, but

X-linked Sex linked describes the sex-specific patterns of inheritance and presentation when a gene mutation (allele) is present on a sex chromosome (allosome) rather than a non-sex chromosome (autosome). In humans, these are termed X-linked recessive, ...

. Taken together, sphingolipidoses have an incidence of approximately 1 in 10,000.

Enzyme replacement therapy Enzyme replacement therapy (ERT) is a medical treatment which replaces an enzyme that is deficient or absent in the body. Usually, this is done by giving the patient an intravenous (IV) infusion of a solution containing the enzyme. ERT is availa ...

is available mainly to treat Fabry disease and Gaucher disease and people with these types of sphingolipidoses may live well into adulthood. Generally, the other types are fatal by age 1 to 5 years for infantile forms, but progression may be mild for juvenile-onset or adult-onset forms. Alternatively, some of the sphingolipidoses may be classified into either GM1 gangliosidoses or

GM2 gangliosidoses The GM2 gangliosidoses are a group of three related genetic disorders that result from a deficiency of the enzyme beta-hexosaminidase. This enzyme catalyzes the biodegradation of fatty acid derivatives known as gangliosides. The diseases are bett ...

belongs to the latter.

Other

Other lipid storage disorders that generally are not classified as sphingolipidoses include

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 lead ...

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-acetylgalactosaminidas ...

, and

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 acid lipase (LAL) enzyme. This enzyme plays an important role in breakin ...

Genetics

Lipid storage diseases can be inherited two ways: Autosomal recessive inheritance occurs when both parents carry and pass on a copy of the faulty gene, but neither parent show signs and symptoms of the condition and is not affected by the disorder. Each child born to these parents have a 25 percent chance of inheriting both copies of the defective gene, a 50 percent chance of being a carrier, and a 25 percent chance of not inheriting either copy of the defective gene. Children of either gender may be affected by an autosomal recessive this pattern of inheritance.

X-linked recessive X-linked recessive inheritance is a mode of inheritance in which a mutation in a gene on the X chromosome causes the phenotype to be always expressed in males (who are necessarily homozygous for the gene mutation because they have one X and one Y ...

(or sex linked) inheritance occurs when the mother carries the affected gene on the X chromosome that has determined the child's gender and passes it to her son. Sons of carriers have a 50 percent chance of inheriting the disorder. Daughters have a 50 percent chance of inheriting the X-linked chromosome, but usually are not severely affected by the disorder. Affected men do not pass the disorder to their sons, but their daughters will be carriers for the disorder.

Diagnosis

Diagnosis of the lipid storage disorders can be achieved through the use of several tests. These tests include clinical examination, biopsy, genetic testing, molecular analysis of cells or tissues, and enzyme assays. Certain forms of this disease also can be diagnosed through urine testing, which detects the stored material.

Prenatal testing Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problems with the pregnancy as early as possible. These may be anatomic and physiologic problems with the health o ...

also is available to determine whether the fetus will have the disease or is a carrier.

Treatment

There are no specific treatments for lipid storage disorders; however, there are some highly effective enzyme replacement therapies for people with type 1 Gaucher disease and some patients with type 3 Gaucher disease. There are other treatments such as the prescription of certain drugs such as phenytoin and carbamazepine to treat pain for patients with

. Furthermore, gene therapies and bone marrow transplantation may prove to be effective for certain lipid storage disorders. Diet restrictions do not help prevent the buildup of lipids in the tissues.

References

External links

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