Glutaric acidemia type 1
Encyclopedia
Glutaric acidemia type 1 (or "Glutaric Aciduria", "GA1", or "GAT1") is an inherited disorder in which the body is unable to break down completely the amino acid
s lysine
, hydroxylysine and tryptophan
. Excessive levels of their intermediate breakdown products (glutaric acid
, glutaryl-CoA
, 3-hydroxyglutaric acid, glutaconic acid
) can accumulate and cause damage to the brain
(and also other organs), but particularly the basal ganglia
, which are regions that help regulate movement. GA1 causes secondary carnitine deficiency, as glutaric acid
, like other organic acid
s, is detoxified by carnitine
. Mental retardation
may also occur.
). Macrocephaly is amongst the earliest signs of GA1. It is thus important to investigate all cases of macrocephaly of unknown origins for GCDH deficiency, given the importance of the early diagnosis of GA1.
Macrocephaly is a "pivotal clinical sign" of many neurological diseases. Physicians and parents should be aware of the benefits of investigating for an underlying neurological disorder, particularly a neurometabolic one, in children with head circumferences in the highest percentiles.
s, jerking, rigidity or decreased muscle tone and muscle weakness (which may be the result of secondary carnitine deficiency). Glutaric aciduria type 1, in many cases, can be defined as a cerebral palsy
of genetic origins.
A common way to manage striatal necrosis is to provide special seating. These special wheelchairs are designed to limit abnormal movements. However, spasticity can be worsened by constraint.
Parents and caregivers can provide a more interactive occupational therapy by enabling the child to use his or her own excessive postural muscle tone to his or her own advantage (see picture; note the care with which minimal pressure is applied while ensuring safety).
The excessive tone can also be managed with "jolly jumpers" and other aids to the upright stance that do not constrain the child but help him or her gradually tone down the rigidity.
.
depletion. Whole-blood carnitine can be raised by oral supplementation. However, this does not significantly change blood concentrations of glutarylcarnitine or esterified carnitine, suggesting that oral supplementation is suboptimal in raising tissue levels of carnitine. In the field of clinical nutrition, researchers come to the same conclusion, that oral carnitine raises plasma levels but doesn't affect muscle carnitine, where most of it is stored and used.
Formulas such as XLys, XTrp Analog, XLys, XTrp Maxamaid, XLys, XTrp Maxamum or Glutarex 1 are designed to provide amino acids other than lysine and tryptophan, in order to tentatively prevent protein malnutrition.
The entry of tryptophan to the brain is crucial in the proper synthesis of the neurotransmitter serotonin
in the brain. One way to acutely cause depression or bulimia or anxiety in humans, in order to assess an individual's vulnerability to those disorders, is to supplement with a formula with all or most amino acids except tryptophan. The protein synthesis elicited by the amino acids leads circulating amino acids, including tryptophan, to be incorporated into proteins. Tryptophan thus lowers in the brain as a result of the protein synthesis enhancement (causing circulating tryptophan to lower more than other amino acids), and perhaps also competition of large neutral amino acids for transport across the blood-brain barrier
through the large neutral amino acid transporter 1 (LNAA1). The consequence is acute tryptophan depletion (ATD) in the brain and a consecutive lowering of serotonin
synthesis. ATD, which is basically a diagnostic procedure, is not a treatment for GA1.
In the Amish
community, where GA1 is overrepresented (Morton, 2003), patients with GA1 did not and still don't receive tryptophan-free formulas, neither as the sole source of amino acids, nor as a supplement to protein restriction. Doctor D. Holmes Morton
, the 1993 Albert Schweitzer Prize for Humanitarianism
laureate, is taking care of patients affected with GA1 and other metabolic diseases in this community in his Clinic for Special Children
.
5-hydroxytryptophan, the precursor of serotonin that is not metabolized to glutaryl-CoA, glutaric acid and secondary metabolites, could be used as an adjunct to selective tryptophan restriction, considering the risks associated with the procedure. However, the evidence in favour of selective tryptophan restriction remains insufficient and the consensus evolves towards the restriction of lysine only (Kolker & al. 2006).
Lysine restriction, as well as carnitine supplementation, are considered the best predictors of a good prognosis for GA1 (Kolker & al., 2006). This excludes, however, patients who already suffered an encephalopathic crisis, for whom the prognosis is more related to the treatment of their acquired disorder (striatal necrosis, frontotemporal atrophy).
and hydroxylysine degradation, as lysine is one of the most abundant amino acids and tryptophan is one the least abundant amino acids.
While GCDH deficiency is a rare disease, GLO deficiency is the most common of metabolic diseases affecting Humanity, limiting ascorbic acid biosynthesis to a minute fraction of what other non-primate species synthesize. It was thus called by OMIM (Online Mendeleian Inheritance in Man) a "public" error of metabolism. Ascorbic acid
(Vitamin C
) is a necessary cofactor for the utilization of lysine in collagen synthesis. Collagen, the most abundant protein in the human body, requires great amounts of lysine, the most abundant amino acids in proteins. Ascorbic acid, the main hydroxyl radical quencher, works as the cofactor providing the hydroxyl radical required to collagen cross-linking; lysine thus becomes hydroxylysine.
GA1 worsens during stresses and catabolic episodes, such as fasts and infections. Endogenous catabolism of proteins could be an important route for glutaric acid production. It thus follows that collagen breakdown (and protein breakdown in general) should be prevented by all possible means.
Ascorbic acid is used to prevent multiple organ failure and to lessen mortality and morbidity in intensive care units. It thus appears reasonable to include sufficient doses of ascorbic acid to the treatment protocol during stresses and other challenges to growth in order to stimulate collagen synthesis and thus prevent lysine breakdown.
. This enzyme is involved in degrading the amino acids lysine
, hydroxylysine and tryptophan
. Mutations in the GCDH gene prevent production of the enzyme or result in the production of a defective enzyme with very low residual activity, or an enzyme with relatively high residual activity but still phenotypic consequences. This enzyme deficiency allows glutaric acid, 3-hydroxyglutaric acid and (to a lesser extent) glutaconic acid to build up to abnormal levels, especially at times when the body is under stress. These intermediate breakdown products are particularly prone to affect the basal ganglia, causing many of the signs and symptoms of glutaric acidemia type 1.
Glutaric acidemia type 1 occurs in approximately 1 of every 30,000 to 40,000 births. It is much more common in the Amish
community and in the Ojibway population of Canada
, where up to 1 in 300 newborns may be affected.
Relatives of children with GA1 can have very low GCDH activity: in an early study of GA1, GCDH activity was found to be 38%, 42%, and 42% of controls in three of the four relatives tested. Those levels are close to those found by Christensen & al in some heavily symptomatic GA1-affected children.
This article incorporates public domain text from The U.S. National Library of Medicine
or a basal ganglia
disorder (it is also misdiagnosed as shaken baby syndrome
).
Depending on the paradigm adopted, GA1 will mostly be managed with precursor restriction or with neurorehabilitation (or with incarceration of the parents in the case of presumed shaken baby syndrome).
So-called "orphan diseases", such as GA1, can be adopted into wider groups of diseases (such as carnitine deficiency diseases, cerebral palsies of diverse origins, basal ganglia disorders, and others); Morton at al. (2003b) emphacize that acute striatal necrosis is a distinctive pathologic feature of at least 20 other disorders of very different etiologies (e.g. HIV encephalopathy-AIDS dementia complex
, pneumococcal meningitis
, hypoadrenal crisis, methylmalonic acidemia
, propionic acidemia
, middle cerebral artery
occlusion, hypertensive vasculopathy, acute mycoplasma pneumoniae
infection, 3-nitropropionic acid intoxication, late onset familial dystonia
, cerebrovascular abrupt and severe neonatal asphyxia ("selective neuronal necrosis")).
Amongst 279 patients who had been reported to have GA1, 185 were symptomatic (two thirds); being symptomatic was seen as an indication of "low treatment efficacy". High risk screening, neonatal screening and a diagnosis of macrocephaly
were the ways to identify bearers of the GCDH defective gene who weren't frankly symptomatic. Macrocephaly
remains the main sign of GA1 for those who aren't related to GA1 in any way or benefit from no screening program. GA1 was considered as a "treatable disease".
Two thirds of the patients who have GA1 will receive little benefit from the treatment for GA1 but can benefit from treatments given to victims of middle cerebral artery occlusion, AIDS dementia and other basal ganglia
disorders: brain implant
s, stem cell
neurorestauration, growth factor
s, monoaminergic agents, and many other neurorehabilitation strategies.
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
, hydroxylysine and tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
. Excessive levels of their intermediate breakdown products (glutaric acid
Glutaric acid
Glutaric acid is the organic compound with the formula HO2C3CO2H. Although the related "linear" dicarboxylic acids adipic and succinic acids are water-soluble only to a few percent at room temperature, the water-solubility of glutaric acid is over 50%....
, glutaryl-CoA
Glutaryl-CoA
Glutaryl-coenzyme A is an intermediate in the metabolism of lysine and tryptophan....
, 3-hydroxyglutaric acid, glutaconic acid
Glutaconic acid
trans-Glutaconic acid is an organic compound with formula HO2CCH=CHCH2CO2H. This dicarboxylic acid exists as a colorless solid and is related to the saturated chemical glutaric acid, HO2CC3CO2H. Esters and salts of glutaconic acid are called glutaconates.-Related compounds:The geometric isomer,...
) can accumulate and cause damage to the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
(and also other organs), but particularly the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
, which are regions that help regulate movement. GA1 causes secondary carnitine deficiency, as glutaric acid
Glutaric acid
Glutaric acid is the organic compound with the formula HO2C3CO2H. Although the related "linear" dicarboxylic acids adipic and succinic acids are water-soluble only to a few percent at room temperature, the water-solubility of glutaric acid is over 50%....
, like other organic acid
Organic acid
An organic acid is an organic compound with acidic properties. The most common organic acids are the carboxylic acids, whose acidity is associated with their carboxyl group –COOH. Sulfonic acids, containing the group –SO2OH, are relatively stronger acids. The relative stability of the conjugate...
s, is detoxified by carnitine
Carnitine
Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids for the generation of metabolic energy. It is widely...
. Mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
may also occur.
Signs and symptoms
The severity of glutaric acidemia type 1 varies widely; some individuals are only mildly affected, while others have severe problems. GA1 can be defined as two clinical entities: GA1 before the encephalopathic crisis and GA1 after the encephalopathic crisis.Macrocephaly
Babies with glutaric acidemia type 1 often are born with unusually large heads (macrocephalyMacrocephaly
Macrocephaly , occurs when the head is abnormally large; this includes the scalp, the cranial bone, and the contents of the cranium.-Causes:...
). Macrocephaly is amongst the earliest signs of GA1. It is thus important to investigate all cases of macrocephaly of unknown origins for GCDH deficiency, given the importance of the early diagnosis of GA1.
Macrocephaly is a "pivotal clinical sign" of many neurological diseases. Physicians and parents should be aware of the benefits of investigating for an underlying neurological disorder, particularly a neurometabolic one, in children with head circumferences in the highest percentiles.
Neuromotor aspects
Affected individuals may have difficulty moving and may experience spasmSpasm
In medicine a spasm is a sudden, involuntary contraction of a muscle, a group of muscles, or a hollow organ, or a similarly sudden contraction of an orifice. It is sometimes accompanied by a sudden burst of pain, but is usually harmless and ceases after a few minutes...
s, jerking, rigidity or decreased muscle tone and muscle weakness (which may be the result of secondary carnitine deficiency). Glutaric aciduria type 1, in many cases, can be defined as a cerebral palsy
Cerebral palsy
Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....
of genetic origins.
Occupational therapy
Parents and caregivers can provide a more interactive occupational therapy by enabling the child to use his or her own excessive postural muscle tone to his or her own advantage (see picture; note the care with which minimal pressure is applied while ensuring safety).
The excessive tone can also be managed with "jolly jumpers" and other aids to the upright stance that do not constrain the child but help him or her gradually tone down the rigidity.
Bleeding abnormalities
Some individuals with glutaric acidemia have developed bleeding in the brain or eyes that could be mistaken for the effects of child abuseChild abuse
Child abuse is the physical, sexual, emotional mistreatment, or neglect of a child. In the United States, the Centers for Disease Control and Prevention and the Department of Children And Families define child maltreatment as any act or series of acts of commission or omission by a parent or...
.
Correction of secondary carnitine depletion
Like many other organic acidemias, GA1 causes carnitineCarnitine
Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids for the generation of metabolic energy. It is widely...
depletion. Whole-blood carnitine can be raised by oral supplementation. However, this does not significantly change blood concentrations of glutarylcarnitine or esterified carnitine, suggesting that oral supplementation is suboptimal in raising tissue levels of carnitine. In the field of clinical nutrition, researchers come to the same conclusion, that oral carnitine raises plasma levels but doesn't affect muscle carnitine, where most of it is stored and used.
- In contrast, regular intravenous infusions of carnitine caused distinct clinical improvements: "decreased frequency of decompensations, improved growth, improved muscle strength and decreased reliance on medical foods with liberalization of protein intake."
- Choline increases carnitine uptake and retention. Choline supplements are inexpensive, safe (probably even in all children requiring anticholinergics) and can provide spectacular evidence of the suboptimal efficiency of carnitine supplementation by increasing exercise tolerance, truncal tone and general well-being.
Tryptophan
Formulas such as XLys, XTrp Analog, XLys, XTrp Maxamaid, XLys, XTrp Maxamum or Glutarex 1 are designed to provide amino acids other than lysine and tryptophan, in order to tentatively prevent protein malnutrition.
The entry of tryptophan to the brain is crucial in the proper synthesis of the neurotransmitter serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
in the brain. One way to acutely cause depression or bulimia or anxiety in humans, in order to assess an individual's vulnerability to those disorders, is to supplement with a formula with all or most amino acids except tryptophan. The protein synthesis elicited by the amino acids leads circulating amino acids, including tryptophan, to be incorporated into proteins. Tryptophan thus lowers in the brain as a result of the protein synthesis enhancement (causing circulating tryptophan to lower more than other amino acids), and perhaps also competition of large neutral amino acids for transport across the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
through the large neutral amino acid transporter 1 (LNAA1). The consequence is acute tryptophan depletion (ATD) in the brain and a consecutive lowering of serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
synthesis. ATD, which is basically a diagnostic procedure, is not a treatment for GA1.
In the Amish
Amish
The Amish , sometimes referred to as Amish Mennonites, are a group of Christian church fellowships that form a subgroup of the Mennonite churches...
community, where GA1 is overrepresented (Morton, 2003), patients with GA1 did not and still don't receive tryptophan-free formulas, neither as the sole source of amino acids, nor as a supplement to protein restriction. Doctor D. Holmes Morton
D. Holmes Morton
D. Holmes Morton is an American physician specializing in genetic disorders of Old Order Amish and Mennonite children. In 1989 he established the Clinic for Special Children in Strasburg, Pennsylvania to focus on these diseases....
, the 1993 Albert Schweitzer Prize for Humanitarianism
Albert Schweitzer Prize for Humanitarianism
The Albert Schweitzer Prize for Humanitarianism is a prize given to people who made exemplary contributions to humanity and the environment. The goal of the prize is to advance the cause of humanitarianism. The prize was established in 1986 by Albert Toepfer, an international grain merchant from...
laureate, is taking care of patients affected with GA1 and other metabolic diseases in this community in his Clinic for Special Children
Clinic for Special Children
The Clinic for Special Children is a gene research clinic located in Strasburg, Pennsylvania. The facility, established by Dr. D. Holmes Morton, specializes in genetic problems of the plain sects such as the Amish and Old Order Mennonites....
.
5-hydroxytryptophan, the precursor of serotonin that is not metabolized to glutaryl-CoA, glutaric acid and secondary metabolites, could be used as an adjunct to selective tryptophan restriction, considering the risks associated with the procedure. However, the evidence in favour of selective tryptophan restriction remains insufficient and the consensus evolves towards the restriction of lysine only (Kolker & al. 2006).
Lysine
Lysine restriction, as well as carnitine supplementation, are considered the best predictors of a good prognosis for GA1 (Kolker & al., 2006). This excludes, however, patients who already suffered an encephalopathic crisis, for whom the prognosis is more related to the treatment of their acquired disorder (striatal necrosis, frontotemporal atrophy).
Protein restriction
Vegetarian diets and, for younger children, breastfeeding are common ways to limit protein intake without endangering tryptophan transport to the brain.Lysine and hydroxylysine anabolic pathway enhancement
A possible way to prevent the build-up of metabolites is to limit lysineLysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
and hydroxylysine degradation, as lysine is one of the most abundant amino acids and tryptophan is one the least abundant amino acids.
Interaction of GCDH deficiency with GLO deficiency
While GCDH deficiency is a rare disease, GLO deficiency is the most common of metabolic diseases affecting Humanity, limiting ascorbic acid biosynthesis to a minute fraction of what other non-primate species synthesize. It was thus called by OMIM (Online Mendeleian Inheritance in Man) a "public" error of metabolism. Ascorbic acid
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
(Vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
) is a necessary cofactor for the utilization of lysine in collagen synthesis. Collagen, the most abundant protein in the human body, requires great amounts of lysine, the most abundant amino acids in proteins. Ascorbic acid, the main hydroxyl radical quencher, works as the cofactor providing the hydroxyl radical required to collagen cross-linking; lysine thus becomes hydroxylysine.
GA1 worsens during stresses and catabolic episodes, such as fasts and infections. Endogenous catabolism of proteins could be an important route for glutaric acid production. It thus follows that collagen breakdown (and protein breakdown in general) should be prevented by all possible means.
Ascorbic acid is used to prevent multiple organ failure and to lessen mortality and morbidity in intensive care units. It thus appears reasonable to include sufficient doses of ascorbic acid to the treatment protocol during stresses and other challenges to growth in order to stimulate collagen synthesis and thus prevent lysine breakdown.
Tryptophan anabolic pathway enhancement
The conversion of tryptophan to serotonin and other metabolites depends on vitamin B6. If tryptophan catabolism has any impact on brain glutaric acid and other catabolite levels, vitamin B6 levels should be routinely assayed and normalized in the course of the treatment of GA1.Management of intercurrent illnesses
Stress caused by infection, fever or other demands on the body may lead to worsening of the signs and symptoms, with only partial recovery.Genetics
The condition is inherited in an autosomal recessive pattern: mutated copies of the gene GCDH must be provided by both parents to cause glutaric acidemia type 1. The GCDH gene encodes the enzyme glutaryl-CoA dehydrogenaseGlutaryl-CoA dehydrogenase
Glutaryl-CoA dehydrogenase is an enzyme acting upon glutaryl-coenzyme A, creating crotonyl-coenzyme A.It plays a role in the metabolism of lysine, hydroxylysine and tryptophan.-Pathology:...
. This enzyme is involved in degrading the amino acids lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
, hydroxylysine and tryptophan
Tryptophan
Tryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
. Mutations in the GCDH gene prevent production of the enzyme or result in the production of a defective enzyme with very low residual activity, or an enzyme with relatively high residual activity but still phenotypic consequences. This enzyme deficiency allows glutaric acid, 3-hydroxyglutaric acid and (to a lesser extent) glutaconic acid to build up to abnormal levels, especially at times when the body is under stress. These intermediate breakdown products are particularly prone to affect the basal ganglia, causing many of the signs and symptoms of glutaric acidemia type 1.
Glutaric acidemia type 1 occurs in approximately 1 of every 30,000 to 40,000 births. It is much more common in the Amish
Amish
The Amish , sometimes referred to as Amish Mennonites, are a group of Christian church fellowships that form a subgroup of the Mennonite churches...
community and in the Ojibway population of Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
, where up to 1 in 300 newborns may be affected.
Relatives of children with GA1 can have very low GCDH activity: in an early study of GA1, GCDH activity was found to be 38%, 42%, and 42% of controls in three of the four relatives tested. Those levels are close to those found by Christensen & al in some heavily symptomatic GA1-affected children.
This article incorporates public domain text from The U.S. National Library of Medicine
Epistemology
GA1 can be described as a metabolic disease, a neurometabolic disease, a cerebral palsyCerebral palsy
Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....
or a basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
disorder (it is also misdiagnosed as shaken baby syndrome
Shaken baby syndrome
Shaken baby syndrome is a triad of medical symptoms: subdural hematoma, retinal hemorrhage, and brain swelling from which doctors, consistent with current medical understanding, infer child abuse caused by intentional shaking...
).
Depending on the paradigm adopted, GA1 will mostly be managed with precursor restriction or with neurorehabilitation (or with incarceration of the parents in the case of presumed shaken baby syndrome).
So-called "orphan diseases", such as GA1, can be adopted into wider groups of diseases (such as carnitine deficiency diseases, cerebral palsies of diverse origins, basal ganglia disorders, and others); Morton at al. (2003b) emphacize that acute striatal necrosis is a distinctive pathologic feature of at least 20 other disorders of very different etiologies (e.g. HIV encephalopathy-AIDS dementia complex
AIDS dementia complex
AIDS dementia complex is a common neurological disorder associated with HIV infection and AIDS. It is a metabolic encephalopathy induced by HIV infection and fueled by immune activation of brain macrophages and microglia...
, pneumococcal meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
, hypoadrenal crisis, methylmalonic acidemia
Methylmalonic acidemia
Methylmalonic acidemia , also called methylmalonic aciduria, is an autosomal recessive metabolic disorder. It is a classical type of organic acidemia....
, propionic acidemia
Propionic acidemia
Propionic acidemia, also known as propionic aciduria, propionyl-CoA carboxylase deficiency and ketotic glycinemia, is an autosomal recessive metabolic disorder, classified as a branched-chain organic acidemia....
, middle cerebral artery
Middle cerebral artery
-External links:*...
occlusion, hypertensive vasculopathy, acute mycoplasma pneumoniae
Mycoplasma pneumoniae
Mycoplasma pneumoniae is a very small bacterium in the class Mollicutes.It causes the disease mycoplasma pneumonia, a form of atypical bacterial pneumonia, and is related to cold agglutinin disease.-Cell wall/Treatment:...
infection, 3-nitropropionic acid intoxication, late onset familial dystonia
Dystonia
Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
, cerebrovascular abrupt and severe neonatal asphyxia ("selective neuronal necrosis")).
Amongst 279 patients who had been reported to have GA1, 185 were symptomatic (two thirds); being symptomatic was seen as an indication of "low treatment efficacy". High risk screening, neonatal screening and a diagnosis of macrocephaly
Macrocephaly
Macrocephaly , occurs when the head is abnormally large; this includes the scalp, the cranial bone, and the contents of the cranium.-Causes:...
were the ways to identify bearers of the GCDH defective gene who weren't frankly symptomatic. Macrocephaly
Macrocephaly
Macrocephaly , occurs when the head is abnormally large; this includes the scalp, the cranial bone, and the contents of the cranium.-Causes:...
remains the main sign of GA1 for those who aren't related to GA1 in any way or benefit from no screening program. GA1 was considered as a "treatable disease".
Two thirds of the patients who have GA1 will receive little benefit from the treatment for GA1 but can benefit from treatments given to victims of middle cerebral artery occlusion, AIDS dementia and other basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
disorders: brain implant
Brain implant
Brain implants, often referred to as neural implants, are technological devices that connect directly to a biological subject's brain - usually placed on the surface of the brain, or attached to the brain's cortex...
s, stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
neurorestauration, growth factor
Growth factor
A growth factor is a naturally occurring substance capable of stimulating cellular growth, proliferation and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes....
s, monoaminergic agents, and many other neurorehabilitation strategies.