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Autosomal Dominant GTP Cyclohydrolase I Deficiency
Autosomal dominant GTP cyclohydrolase I deficiency (AD-GTPCHD) is a disease caused by dysfunction of GTP cyclohydrolase I, an enzyme that plays an important role in the synthesis of tetrahydrobiopterin, and, as a consequence, of dopamine. This condition is one of the six known causes of tetrahydrobiopterin deficiency and is the most frequently-reported cause of dopa-responsive dystonia. Symptoms In more than half the cases, the clinical picture is dominated by postural or action-induced dystonia of one or both lower limbs manifesting as gait difficulties. Dystonia gradually worsens during the day and becomes less pronounced after a period of rest. The fluctuating pattern is highly typical of this disease, especially in the first 30 years, after which this diurnal variation becomes less prominent. The typical age at onset is during the first decade of life, although an onset in the second decade of life is also common, and in rare cases the disease may present itself in the first 12 ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GTP Cyclohydrolase I
GTP cyclohydrolase I (GTPCH) () is a member of the GTP cyclohydrolase family of enzymes. GTPCH is part of the folate and biopterin biosynthesis pathways. It is responsible for the hydrolysis of guanosine triphosphate (GTP) to form 7,8-dihydroneopterin triphosphate (7,8-DHNP-3'-TP, 7,8-NH2-3'-TP). Gene GTPCH is encoded by the gene ''GCH1''. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all of the variants give rise to a functional enzyme. Clinical significance At least 94 disease-causing mutations in this gene have been discovered. Mutations in this gene are associated with two disorders: autosomal recessive GTP cyclohydrolase I deficiency and autosomal dominant GTP cyclohydrolase I deficiency. These may present with malignant phenylketonuria (PKU) and hyperphenylalaninemia (HPA) and lead to a lack of certain neurotransmitters (dopamine, norepinephrine, epinephrine and serotonin). The dominant form, with m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Dopamine Agonist
A dopamine agonist (DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D2-like and D1-like, and they are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the D2-like family includes D2, D3 and D4 receptors. Dopamine agonists are primarily used to treat Parkinson's disease. They are also used, to a far lesser extent, in treating hyperprolactinemia and restless legs syndrome. They are not intended for treatment of clinical depression, and studies have shown severe detrimental side effects resulting from off-label use of dopamine agonists in treating depression, particularly in their tendency to produce impulse control disorders and extreme cases of withdrawal syndrome. Medical uses Parkinson's disease Dopamine agonists are mainly used in the treatment of Parkinson's disease. The cause of Parkinson's is not fully known but genetic factors, for example specific genetic mutations, and environmen ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Autosomal Dominant Disorders
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 (''de novo'') 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 (see Sex linkage). 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 d ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Online Mendelian Inheritance In Man
Online Mendelian Inheritance in Man (OMIM) is a continuously updated catalog of human genes and genetic disorders and traits, with a particular focus on the gene-phenotype relationship. , approximately 9,000 of the over 25,000 entries in OMIM represented phenotypes; the rest represented genes, many of which were related to known phenotypes. Versions and history OMIM is the online continuation of Dr. Victor A. McKusick's ''Mendelian Inheritance in Man'' (MIM), which was published in 12 editions between 1966 and 1998.McKusick, V. A. ''Mendelian Inheritance in Man. Catalogs of Autosomal Dominant, Autosomal Recessive and X-Linked Phenotypes.'' Baltimore, MD: Johns Hopkins University Press, 1st ed, 1996; 2nd ed, 1969; 3rd ed, 1971; 4th ed, 1975; 5th ed, 1978; 6th ed, 1983; 7th ed, 1986; 8th ed, 1988; 9th ed, 1990; 10th ed, 1992. Nearly all of the 1,486 entries in the first edition of MIM discussed phenotypes. MIM/OMIM is produced and curated at the Johns Hopkins School of Medicine ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Autosomal Recessive GTP Cyclohydrolase I Deficiency
Autosomal recessive GTP cyclohydrolase I deficiency (AR-GTPCHD) is a disorder associated with the deficient operation of the enzyme GTP cyclohydrolase I. The condition leads to insufficient production of the cofactor tetrahydrobiopterin necessary for the proper synthesis of dopamine and serotonin and for maintenance of adequate levels of phenylalanine. As of 2020, autosomal recessive GTP cyclohydrolase I deficiency was one of the six known causes of tetrahydrobiopterin deficiency. It is also considered part of the spectrum of dopa-responsive dystonias. Symptoms Patients may present with developmental delay, axial hypotonia, delayed development of speech, or dysarthria. The list of possible motor disturbances includes dystonia, oculogyric crises, parkinsonism/hypokinesia. Patients may have a number of psychiatric symptoms. Biochemically, patients present with hyperphenylalaninemia, and usually have decreased levels of biopterin and neopterin in urine and in dry blood spots. Treatme ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
International Parkinson And Movement Disorder Society
International is an adjective (also used as a noun) meaning "between nations". International may also refer to: Music Albums * ''International'' (Kevin Michael album), 2011 * ''International'' (New Order album), 2002 * ''International'' (The Three Degrees album), 1975 *''International'', 2018 album by L'Algérino Songs * The Internationale, the left-wing anthem * "International" (Chase & Status song), 2014 * "International", by Adventures in Stereo from ''Monomania'', 2000 * "International", by Brass Construction from ''Renegades'', 1984 * "International", by Thomas Leer from ''The Scale of Ten'', 1985 * "International", by Kevin Michael from ''International'' (Kevin Michael album), 2011 * "International", by McGuinness Flint from ''McGuinness Flint'', 1970 * "International", by Orchestral Manoeuvres in the Dark from '' Dazzle Ships'', 1983 * "International (Serious)", by Estelle from '' All of Me'', 2012 Politics * Political international, any transnational organization of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tyrosine Hydroxylase
Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA). It does so using molecular oxygen (O2), as well as iron (Fe2+) and tetrahydrobiopterin as cofactors. L-DOPA is a precursor for dopamine, which, in turn, is a precursor for the important neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). Tyrosine hydroxylase catalyzes the rate limiting step in this synthesis of catecholamines. In humans, tyrosine hydroxylase is encoded by the ''TH'' gene, and the enzyme is present in the central nervous system (CNS), peripheral sympathetic neurons and the adrenal medulla. Tyrosine hydroxylase, phenylalanine hydroxylase and tryptophan hydroxylase together make up the family of aromatic amino acid hydroxylases (AAAHs). Reaction Tyrosine hydroxylase catalyzes the reaction in which L-tyrosine is hydroxylated in the meta position to obtain L- ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tyrosine Hydroxylase Deficiency
Tyrosine hydroxylase deficiency (THD) is a disorder caused by disfunction of tyrosine hydroxylase, an enzyme involved in the biosynthesis of dopamine. This condition is one of the causes of dopa-responsive dystonia. Symptoms Patients present with symptoms reflecting the decreased production of dopamine: hypokinetic-rigid syndrome, dystonia, complex encephalopathy. Symptom severity and age at onset are highly variable. A review published on GeneReviews and last updated in 2017 suggests the approximate subdivision of patients into three groups based on differences in severity of symptoms, nature of symptoms, and age at onset. A review published more recently, in 2021, suggests that the disease may have a more gradual and overlapping spectrum, and categorization may be imprecise. According to the classification on GeneReviews, three approximate phenotypes could be discerned: * 1. TH-deficient dopa-responsive dystonia - the mildest phenotype with onset between 1 and 12 years of age, w ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
COMT Inhibitors
A catechol-''O''-methyltransferase (COMT) inhibitor is a drug that inhibits the enzyme catechol-''O''-methyltransferase. This enzyme methylates catecholamines such as dopamine, norepinephrine and epinephrine. It also methylates levodopa. COMT inhibitors are indicated for the treatment of Parkinson's disease in combination with levodopa and an aromatic L-amino acid decarboxylase inhibitor (e.g. carbidopa or benserazide). The therapeutic benefit of using a COMT inhibitor is based on its ability to prevent the methylation of levodopa to 3-''O''-methyldopa, thus increasing the bioavailability of levodopa. COMT inhibitors significantly decrease off time in people with Parkinson's disease also taking carbidopa/levodopa. List of COMT inhibitors * entacapone (Comtan, Comtess, Stalevo) *nebicapone * nitecapone * opicapone (Ongentys) * tolcapone (Tasmar) Entacapone and opicapone are peripheral inhibitors, unable to cross the blood-brain barrier. Tolcapone is able to cross the blood-b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Anticholinergic Drug
Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system. These agents inhibit the parasympathetic nervous system by selectively blocking the binding of ACh to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movement of smooth muscles present in the gastrointestinal tract, urinary tract, lungs, sweat glands, and many other parts of the body. In broad terms, anticholinergics are divided into two categories in accordance with their specific targets in the central and peripheral nervous system and at the neuromuscular junction: antimuscarinic agents, and antinicotinic agents ( ganglionic blockers, neuromuscular blockers). The term "anticholinergic" is typically used to refer to antimuscarinics which competitively inhibit the binding of ACh to muscarinic acetylcholine receptors; such agent ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bromocriptine
Bromocriptine, originally marketed as Parlodel and subsequently under many brand names, is an ergoline derivative and dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease, hyperprolactinaemia, neuroleptic malignant syndrome, and, as an adjunct, type 2 diabetes. It was patented in 1968 and approved for medical use in 1975. Medical uses Bromocriptine is used to treat acromegaly and conditions associated with hyperprolactinemia like amenorrhea, infertility, hypogonadism, and prolactin-secreting adenomas. It is also used to prevent ovarian hyperstimulation syndrome For label updates seFDA index page for NDA 017962 and to treat Parkinson's disease. Since the late 1980s it has been used, off-label, to reduce the symptoms of cocaine withdrawal but the evidence for this use is poor. A quick-release formulation of bromocriptine, Cycloset, is also used to treat type 2 diabetes.. For label updates seFDA index page for NDA 020866 When administered within ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pramipexole
Pramipexole, sold under the brand Mirapex among others, is medication used to treat Parkinson's disease (PD) and restless legs syndrome (RLS). In Parkinson's disease it may be used alone or together with levodopa. It is taken by mouth. Pramipexole is a dopamine agonist of the non-ergoline class. Studies have shown detrimental side effects resulting from off-label use of pramipexole or other dopamine agonists in treating clinical depression. Pramipexole was approved for medical use in the United States in 1997. Use in pregnancy and breastfeeding is of unclear safety. It is available as a generic medication. In 2020, it was the 193rd most commonly prescribed medication in the United States, with more than 2million prescriptions. Medical uses Pramipexole is used in the treatment of Parkinson's disease (PD) and restless legs syndrome (RLS). Use in pregnancy and breastfeeding is of unclear safety. It is occasionally prescribed off-label for depression. Its effectiveness as an an ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
