A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders are the most common, the term is mostly used when discussing disorders with a single genetic cause, either in a gene or chromosome. The mutation responsible can occur spontaneously before embryonic development, or it can be inherited from two parents who are carriers of a faulty gene or from a parent with the disorder. When the genetic disorder is inherited from one or both parents, it is also classified as a hereditary disease. Some disorders are caused by a mutation on the X chromosome and have X-linked inheritance. Very few disorders are inherited on the Y chromosome or mitochondrial DNA.
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and the second recessive. This state of having two different variants of the same gene on each chromosome is originally caused by a mutation in one of the genes, either new or inherited. The terms autosomal dominant or autosomal recessive are used to describe gene variants on non-sex chromosomes (autosomes) and their associated traits, while those on sex chromosomes (allosomes) are termed X-linked dominant, X-linked recessive or Y-linked; these have an inheritance and presentation pattern that depends on the sex of both the parent and the child. Since there is only one copy of the Y chromosome, Y-linked traits cannot be dominant or recessive. Additionally, there are other forms of dominance such as incomplete dominance, in which a gene variant has a partial effect compared to when it is present on both chromosomes, and co-dominance, in which different variants on each chromosome both show their associated traits.
Gaucher's disease or Gaucher disease (GD) is a genetic disorder in which glucocerebroside accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue, anemia, low blood platelet count and enlargement of the liver and spleen, and is caused by a hereditary deficiency of the enzyme glucocerebrosidase, which acts on glucocerebroside. When the enzyme is defective, glucocerebroside accumulates, particularly in white blood cells and especially in macrophages. Glucocerebroside can collect in the spleen, liver, kidneys, lungs, brain, and bone marrow.
Lysosomal storage diseases are a group of over 70 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomes 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.
Alpha-mannosidosis is a lysosomal storage disorder, first described by Swedish physician Okerman in 1967. In humans it is known to be caused by an autosomal recessive genetic mutation in the gene MAN2B1, located on chromosome 19, affecting the production of the enzyme alpha-D-mannosidase, resulting in its deficiency. Consequently, if both parents are carriers, there will be a 25% chance with each pregnancy that the defective gene from both parents will be inherited, and the child will develop the disease. There is a two in three chance that unaffected siblings will be carriers. In livestock alpha-mannosidosis is caused by chronic poisoning with swainsonine from locoweed.
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 and in females who are homozygous for the gene mutation, see zygosity. Females with one copy of the mutated gene are carriers.
Mulibrey nanism is a rare autosomal recessive congenital disorder. It causes severe growth failure along with abnormalities of the heart, muscle, liver, brain and eye. TRIM37 is responsible for various cellular functions including developmental patterning.
Isovaleric acidemia is a rare autosomal recessive metabolic disorder which disrupts or prevents normal metabolism of the branched-chain amino acid leucine. It is a classical type of organic acidemia.
Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia. The condition gets its name from the distinctive sweet odor of affected infants' urine and earwax, particularly prior to diagnosis and during times of acute illness.
Glycogen storage disease type III (GSD III) is an autosomal recessive metabolic disorder and inborn error of metabolism (specifically of carbohydrates) characterized by a deficiency in glycogen debranching enzymes. It is also known as Cori's disease in honor of the 1947 Nobel laureates Carl Cori and Gerty Cori. Other names include Forbes disease in honor of clinician Gilbert Burnett Forbes (1915–2003), an American physician who further described the features of the disorder, or limit dextrinosis, due to the limit dextrin-like structures in cytosol. Limit dextrin is the remaining polymer produced after hydrolysis of glycogen. Without glycogen debranching enzymes to further convert these branched glycogen polymers to glucose, limit dextrinosis abnormally accumulates in the cytoplasm.
Glycine encephalopathy is a rare autosomal recessive disorder of glycine metabolism. After phenylketonuria, glycine encephalopathy is the second most common disorder of amino acid metabolism. The disease is caused by defects in the glycine cleavage system, an enzyme responsible for glycine catabolism. There are several forms of the disease, with varying severity of symptoms and time of onset. The symptoms are exclusively neurological in nature, and clinically this disorder is characterized by abnormally high levels of the amino acid glycine in bodily fluids and tissues, especially the cerebrospinal fluid.
Congenital muscular dystrophies are autosomal recessively-inherited muscle diseases. They are a group of heterogeneous disorders characterized by muscle weakness which is present at birth and the different changes on muscle biopsy that ranges from myopathic to overtly dystrophic due to the age at which the biopsy takes place.
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 to death. Fucosidosis is one of nine identified glycoprotein storage diseases. The gene encoding the alpha-fucosidase, FUCA 1, was found to be located to the short arm of chromosome 1p36 - p34, by Carrit and co-workers, in 1982.
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.
Peters-plus syndrome or Krause–Kivlin syndrome is a hereditary syndrome defined by Peters' anomaly, dwarfism and intellectual disability.
Hyperprolinemia is a condition which occurs when the amino acid proline is not broken down properly by the enzymes proline oxidase or pyrroline-5-carboxylate dehydrogenase, causing a buildup of proline in the body.
Beta-mannosidase is an enzyme with systematic name beta-D-mannoside mannohydrolase, which is in humans encoded by the MANBA gene. This enzyme catalyses the following chemical reaction
Galactosialidosis, also known as neuraminidase deficiency with beta-galactosidase deficiency, is a genetic lysosomal storage disease. It is caused by a mutation in the CTSA gene which leads to a deficiency of enzymes β-galactosidase and neuraminidase. This deficiency inhibits the lysosomes of cells from functioning properly, resulting in the accumulation of toxic matter within the cell. Hallmark symptoms include abnormal spinal structure, vision problems, coarse facial features, hearing impairment, and intellectual disability. Because galactosialidosis involves the lysosomes of all cells, it can affect various areas of the body, including the brain, eyes, bones, and muscles. Depending on the patient's age at the onset of symptoms, the disease consists of three subtypes: early infantile, late infantile, and juvenile/adult. This condition is considered rare, with most cases having been in the juvenile/adult group of patients.
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), attributable to mutations in the NAGA gene on chromosome 22, which leads to excessive lysosomal accumulation of glycoproteins. A deficiency of the alpha-NAGA enzyme leads to an accumulation of glycosphingolipids throughout the body. This accumulation of sugars gives rise to the clinical features associated with this disorder. Schindler disease is an autosomal recessive disorder, meaning that one must inherit an abnormal allele from both parents in order to have the disease.
Argininemia is an autosomal recessive urea cycle disorder where a deficiency of the enzyme arginase causes a buildup of arginine and ammonia in the blood. Ammonia, which is formed when proteins are broken down in the body, is toxic if levels become too high; the nervous system is especially sensitive to the effects of excess ammonia.
