| Acatalasia | |
|---|---|
| Other names | Acatalasemia, or Takahara's disease [1] : 809 |
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| Basic structure of a peroxisome | |
| Specialty | Endocrinology  |
Acatalasia is an autosomal recessive peroxisomal disorder caused by absent or very low levels of the enzyme catalase. [2] Catalase breaks down hydrogen peroxide in cells into water and oxygen. Low levels of catalase can cause hydrogen peroxide to build up, causing damage to cells.
The disorder is relatively benign, although it causes an increased incidence of oral ulcers, and can under rare circumstances lead to gangrene. [3] [2] Symptoms primarily affect children. [4]
Acatalasia is often the result of mutations in both copies of the CAT gene which codes for the enzyme catalase. [5] There are multiple types of mutation that can cause this condition. Inheriting a single CAT mutation results in hypocatalasia, in which catalase levels are reduced, but still at functional levels. [6]
This disorder is commonly diagnosed pouring hydrogen peroxide on the patient's blood sample. Instead of a very bubbling reaction, blood turns brown-colored, which means the patient suffers from acatalasia. [ citation needed ]
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In parts of Japan, this condition has been found in approximately 1.4% of people. [4] Researchers estimate that the condition occurs in 1 in 20,000 people in Hungary and Switzerland. [5]
In 1948, Dr. Shigeo Takahara (1908–1994), a Japanese otolaryngologist first reported this new disease. [7] He had examined a patient with an oral ulcer. He had spread hydrogen peroxide on the diseased part, but oxygen was not generated due to the lack of catalase. [8]
Catalase is a common enzyme found in nearly all living organisms exposed to oxygen which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting the cell from oxidative damage by reactive oxygen species (ROS). Catalase has one of the highest turnover numbers of all enzymes; one catalase molecule can convert millions of hydrogen peroxide molecules to water and oxygen each second.
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 the age of three to six months of age, with the baby losing the ability to turn over, sit, or crawl. This is then followed by seizures, hearing loss, and inability to move, with death usually occurring by the age of three to five. Less commonly, the disease may occur later in childhood, adolescence, or adulthood. These forms tend to be less severe, but the juvenile form typically results in death by age 15.
Abetalipoproteinemia is a disorder characterized by abnormal absorption of fat and fat-soluble vitamins from food. It is caused by a mutation in microsomal triglyceride transfer protein resulting in deficiencies in the apolipoproteins B-48 and B-100, which are used in the synthesis and exportation of chylomicrons and VLDL respectively. It is not to be confused with familial dysbetalipoproteinemia.
Porphyria cutanea tarda is the most common subtype of porphyria. The disease is named because it is a porphyria that often presents with skin manifestations later in life. The disorder results from low levels of the enzyme responsible for the fifth step in heme production. Heme is a vital molecule for all of the body's organs. It is a component of hemoglobin, the molecule that carries oxygen in the blood.
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.
Chronic granulomatous disease (CGD), also known as Bridges–Good syndrome, chronic granulomatous disorder, and Quie syndrome, is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds used to kill certain ingested pathogens. This leads to the formation of granulomas in many organs. CGD affects about 1 in 200,000 people in the United States, with about 20 new cases diagnosed each year.
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.
Phosphofructokinase deficiency is a rare muscular metabolic disorder, with an autosomal recessive inheritance pattern.
Pyruvate kinase deficiency is an inherited metabolic disorder of the enzyme pyruvate kinase which affects the survival of red blood cells. Both autosomal dominant and recessive inheritance have been observed with the disorder; classically, and more commonly, the inheritance is autosomal recessive. Pyruvate kinase deficiency is the second most common cause of enzyme-deficient hemolytic anemia, following G6PD deficiency.
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, its derivative GA2, the glycolipid globoside in visceral tissues, and some oligosaccharides. Accumulation of these metabolites leads to a progressive destruction of the central nervous system and eventually to death. The rare autosomal recessive neurodegenerative disorder is clinically almost indistinguishable from Tay–Sachs disease, another genetic disorder that disrupts beta-hexosaminidases A and S. There are three subsets of Sandhoff disease based on when first symptoms appear: classic infantile, juvenile and adult late onset.
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the family of mitochondrial diseases, which also include MIDD, MERRF syndrome, and Leber's hereditary optic neuropathy. It was first characterized under this name in 1984. A feature of these diseases is that they are caused by defects in the mitochondrial genome which is inherited purely from the female parent. The most common MELAS mutation is mitochondrial mutation, mtDNA, referred to as m.3243A>G.
Alström syndrome (AS), also called Alström–Hallgren syndrome, is a very rare autosomal recessive genetic disorder characterised by childhood obesity and multiple organ dysfunction. Symptoms include early-onset type 2 diabetes, cone-rod dystrophy resulting in blindness, sensorineural hearing loss and dilated cardiomyopathy. Endocrine disorders typically also occur, such as hypergonadotrophic hypogonadism and hypothyroidism, as well as acanthosis nigricans resulting from hyperinsulinemia. Developmental delay is seen in almost half of people with Alström syndrome.
Ethylmalonic encephalopathy (EE) is a rare autosomal recessive inborn error of metabolism. Patients affected with EE are typically identified shortly after birth, with symptoms including diarrhea, petechiae and seizures. The genetic defect in EE is thought to involve an impairment in the degradation of sulfide intermediates in the body. Hydrogen sulfide then builds up to toxic levels. EE was initially described in 1994. Most cases of EE have been described in individuals of Mediterranean or Arabic origin.
Prolidase deficiency (PD) is an extremely uncommon autosomal recessive disorder associated with collagen metabolism that affects connective tissues and thus a diverse array of organ systems more broadly, though it is extremely inconsistent in its expression.
Congenital hemolytic anemia (CHA) is a diverse group of rare hereditary conditions marked by decreased life expectancy and premature removal of erythrocytes from blood flow. Defects in erythrocyte membrane proteins and red cell enzyme metabolism, as well as changes at the level of erythrocyte precursors, lead to impaired bone marrow erythropoiesis. CAH is distinguished by variable anemia, chronic extravascular hemolysis, decreased erythrocyte life span, splenomegaly, jaundice, biliary lithiasis, and iron overload. Immune-mediated mechanisms may play a role in the pathogenesis of these uncommon diseases, despite the paucity of data regarding the immune system's involvement in CHAs.
Congenital generalized lipodystrophy is an extremely rare autosomal recessive condition, characterized by an extreme scarcity of fat in the subcutaneous tissues. It is a type of lipodystrophy disorder where the magnitude of fat loss determines the severity of metabolic complications. Only 250 cases of the condition have been reported, and it is estimated that it occurs in 1 in 10 million people worldwide.
JAK3 deficiency is a dysfunction in cytokine receptor signalling and their production of cytokines.
Donohue syndrome is an extremely rare and severe genetic disorder. Leprechaunism derives its name from the hallmark elvish features exhibited by the affected individuals. The disease is caused by a mutation in the INSR gene, which contains the genetic information for the formation of insulin receptors. As a result, affected individuals have either a decreased number of insulin receptors, or insulin receptor with greatly impaired functionality. The lack and impairment of insulin receptor functionality leads to an inability to regulate blood glucose levels through severe insulin resistance. This will ultimately lead to affected development of tissues and organs throughout the body. In addition to the physical abnormalities, leprechaunism is also characterized by endocrine system abnormalities that can lead to conditions such as hyperglycemia, hypoglycemia, hyperinsulemia, and the enlargement of certain sex organs such as the penis in males, and the clitoris in females.
Sepiapterin reductase deficiency is an inherited pediatric disorder characterized by movement problems, and most commonly displayed as a pattern of involuntary sustained muscle contractions known as dystonia. Symptoms are usually present within the first year of age, but diagnosis is delayed due to physicians lack of awareness and the specialized diagnostic procedures. Individuals with this disorder also have delayed motor skills development including sitting, crawling, and need assistance when walking. Additional symptoms of this disorder include intellectual disability, excessive sleeping, mood swings, and an abnormally small head size. SR deficiency is a very rare condition. The first case was diagnosed in 2001, and since then there have been approximately 30 reported cases. At this time, the condition seems to be treatable, but the lack of overall awareness and the need for a series of atypical procedures used to diagnose this condition pose a dilemma.
Tyrosinemia type I is a genetic disorder that disrupts the metabolism of the amino acid tyrosine, resulting in damage primarily to the liver along with the kidneys and peripheral nerves. The inability of cells to process tyrosine can lead to chronic liver damage ending in liver failure, as well as renal disease and rickets. Symptoms such as poor growth and enlarged liver are associated with the clinical presentation of the disease. If not detected via newborn screening and management not begun before symptoms appear, clinical manifestation of disease occurs typically within the first two years of life. The severity of the disease is correlated with the timing of onset of symptoms, earlier being more severe. If diagnosed through newborn screening prior to clinical manifestation, and well managed with diet and medication, normal growth and development is possible.