National Organization for Rare Disorders, Inc.
It is possible that the main title of the report Acidemia Isovaleric is not the name you expected.
Isovaleric Acidemia is a hereditary metabolic disorder. It is characterized by a deficiency of the enzyme isovaleryl CoA dehydrogenase. The disorder occurs in both an acute and a chronic intermittent form. In the acute form of Isovaleric Acidemia, vomiting, refusal to eat, and listlessness usually occur. With treatment and low protein diet, the disorder becomes chronically intermittent, and a nearly normal life is possible.
Isovaleric Acidemia is a rare metabolic disorder that occurs in an acute and a chronic intermittent form. The disorder may start any time between the first week of life and adolescence. It is characterized by attacks of vomiting, lack of appetite and listlessness. Infants with Isovaleric Acidemia become increasingly listless, and they sometimes shake or tremble. They often have a lower than normal body temperature (hypothermia). In most cases, a strong odor like that of "sweaty feet" occurs. Intermittent episodes are usually triggered by upper respiratory infections or excessive eating of high protein foods. Severe acidity and the presence of ketone bodies in blood and body tissues (ketoacidosis) usually follows and patients may lapse into a coma.
Ketoacidotic episodes tend to occur frequently in early infancy and young childhood, but their frequency usually diminishes as the patient grows older. Children with Isovaleric Acidemia often show a natural aversion to protein foods, even at a young age.
Isovaleric Acidemia is a genetic disorder inherited through autosomal recessive genes. Symptoms are the result of a deficiency of the enzyme isovaleric co-enzyme A (CoA) dehydrogenase, which is needed for the breakdown of the amino acid leucine. Human traits, including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but generally will not show symptoms of the disorder. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. On average, fifty percent of their children will be carriers of the disease, while 25 percent will receive a normal copy of the gene from each parent for that trait. The risks are the same for each pregnancy.
Isovaleric Acidemia is a rare disorder affecting males and females in equal numbers, usually beginning during infancy.
Methylmalonic Acidemias are a group of organic acidemias. All known organic acidemias are inherited as autosomal recessive traits. Each is caused by an enzymatic defect in the metabolism of one amino acid. Without treatment, this may result in an abnormally high level of acid in the blood and body tissues (acidosis). In acute cases, drowsiness, coma, seizures and mental retardation may occur. Methylmalonic Acidemias may be caused either by a deficiency of the enzyme methylmalonyl CoA mutase, methylmalonyl racemase, or of adenosylcobalamin (a vitamin B12 derivative) synthetic enzymes. Excretion of methylmalonate (a product of amino acid metabolism) in the urine is abnormally high. (For more information, choose Methylmalonic Acidemia" as your search term in the Rare Disease Database.)
Glutaricaciduria II (Glutaric Acidemia II) occurs in two forms during two different stages of life. Both forms are organic acidemias, a group of metabolic disorders characterized by the presence of excess acid in the blood and urine.
Glutaricaciduria IIA (Glutaric Acidemia IIA), the neonatal onset form of Glutaricaciduria, is a very rare, sex-linked hereditary disorder. It is characterized by large amounts of glutaric and other acids in blood and urine. Some researchers believe the disorder is caused by a defect in the breakdown of acyl-CoA compounds.
Glutaricaciduria IIB (Glutaric Acidemia IIB; Ethylmalonic Adipicaciduria), the milder adult onset form of the disorder, is inherited as an autosomal recessive trait. Symptoms may include acidity of the body tissues (acidosis), and a low blood sugar level (hypoglycemia) without an elevated level of ketones in body tissues (ketosis). Large amounts of glutaric acid in the blood and urine are caused by a deficiency of the enzyme "multiple acyl-CoA dehydrogenase". (For more information on this disorder, choose "Glutaricaciduria II" as your search term in the Rare Disease Database").
Maple Syrup Urine Disease is a hereditary disorder resulting from abnormal metabolism of the four "branched chain" amino acids (protein building blocks), leucine, isoleucine, valine, and alloisoleucine. Without treatment, spasticity alternating with poor muscle tone, convulsions, and coma characterize the disorder. It derives its name from the odor of the patients' urine and sweat. (For more information on this disorder, choose "Maple Syrup Urine" as your search term in the Rare Disease Database.)
Non-Ketotic Hyperglycinemia is a genetic disorder characterized as an inborn error of amino acid metabolism. Large amounts of the amino acid glycine tend to accumulate in body fluids, particularly in the cerebrospinal fluid. After severe illness beginning soon after birth, most patients become severely mentally retarded and may develop seizures. (For more information on this disorder, choose "Non-Ketotic Hyperglycinemia" as your search term in the Rare Disease Database.)
Propionic Acidemia is a very rare genetic form of Ketotic Hyperglycinemia. The disorder is characterized by a deficiency of the coenzyme propionyl CoA carboxylase, one of the enzymes necessary in the process of breaking down amino acids. Propionic Acidemia occurs in two forms. One form begins at birth and the other is milder, occurring less frequently, with symptoms starting during later infancy. Without treatment, dehydration, drowsiness, lethargy, vomiting, and in some cases coma may develop. (For more information on this disorder, choose "Propionic Acidemia" as your search term in the Rare Disease Database.)
In some cases, Isovaleric Acidemia may be diagnosed before birth (prenatally) by measuring the concentration of abnormal metabolites in amniotic fluid or the activity of the isovaleryl-CoA dehydrogenase enzyme in fluid or tissue samples obtained from the fetus or uterus during pregnancy (amniocentesis or chorionic villus sampling [CVS]. During amniocentesis, a sample of fluid surrounding the developing fetus is removed and analyzed. CVS involves the removal and examination of tissue from a portion of the placenta. The disorder can be identified at birth through expanded newborn screening with tandem mass spectrometry.
In most affected infants, the disorder is diagnosed or confirmed in the first weeks of life, based upon a thorough clinical evaluation, a detailed patient and family history, and a variety of specialized tests. Laboratory studies (assays) are typically conducted on certain white blood cells (leukocytes) or cultured skin cells (fibroblasts) to confirm deficient activity of the isovaleryl-CoA dehydrogenase enzyme. Additional laboratory studies may reveal excessive levels of acids and increased accumulations of ketone bodies in bodily tissues and fluids (ketoacidosis); increased levels of glycine in the blood and urine (hyperglycinemia and hyperglycinuria); high levels of ammonia in the blood (hyperammonemia); and/or decreased levels of circulating platelets and white blood cells (thrombocytopenia and neutropenia).
The disorder is treated by a diet with moderate restriction of the amino acid leucine and supplementation of L-carnitine. Administration of glycine at 150-300 mg/day is life-saving and may permit normal growth and development. Other treatment is symptomatic and supportive. Genetic counseling is recommended for families of children with Isovaleric Acidemia.
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Sweetman L, Williams JD. Branched chain organic acidurias in The Metabolic and Molecular Basis of Inherited Disease. Scriver C, Beaudet AL, Sly W, Valle D, eds. (McGraw-Hill, New York, 2001), pp. 2125-64.
Mohsen A-W, Vockley J. Biochemical characteristics of recombinant human isovaleryl-CoA dehydrogenase pre-treated with ethylenediaminetetraacetate in Flabins and Flavoproteins. Rudolf Weber, New York, 1999: 515-18.
Vockley J, Rogan PK, Anderson BD, et al. Exon skipping in IVD RNA processing in isovaleric academia caused by point mutations in the coding region of the IVD gene. Am J Hum Genet. 2000;66:356-67.
Mohsen AW, Anderson BD, Volchenboum SL, et al. Characterization of molecular defects in isovaleryl-CoA dehydrogenase in patients with isovaleric academia. Biochemistry. 1998;37:10325-35.
Vockley J, Parimoo B, Tanaka K. Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric academia. Am J Hum Genet. 1991;40:147-57.
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Hine DG, Tanaka K. The identification and the excretion pattern of isovaleryl glucuronide in the urine of patients with isovaleric academia. Pediatr Res. 1984;18:508-12.
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McKusick VA, ed. Online Mendelian Inehritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 243500; Last Update: 4/10/2000.
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