glutaric acidemia type 3

Glutaric acidemia type 3 (GA3) is a rare metabolic disorder characterized by the accumulation or excretion of glutaric acid in the urine due to a deficiency of succinate semialdehyde dehydrogenase, an enzyme involved in the breakdown of certain amino acids and fatty acids [5]. This condition leads to the increased excretion of glutaric acid in the urine, which is a hallmark of GA3 [6].

The symptoms of GA3 can vary widely among affected individuals, but may include developmental delays or intellectual disability, cardiac dysfunction, lethargy, coma, seizures, hypotonia (low muscle tone), and failure to thrive [7]. The prevalence of GA3 is unknown, and there is no distinctive phenotype associated with this condition.

Glutaric acidemia type 3 is a biochemical condition that results from the impaired degradation of lysine, hydroxylysine, and other amino acids, leading to the accumulation of glutaric acid in the body [6]. This condition is often diagnosed through the analysis of urine samples, which show elevated levels of glutaric acid.

It's worth noting that GA3 is a rare disorder, and more research is needed to fully understand its causes, symptoms, and treatment options. However, early diagnosis and management can help alleviate some of the symptoms associated with this condition.

References: [5] PJ Waters · 2018 · Cited by 17 — Glutaric aciduria type 3 (GA3) is associated with decreased conversion of free glutaric acid to glutaryl-coA, reflecting deficiency of succinate ... [6] by J Leandro · 2021 · Cited by 7 — Glutaric aciduria is a biochemical condition characterized by increased excretion of glutaric acid in the urine. Degradation of lysine, but also hydroxylysine ... [7] by NY Saral · 2019 · Cited by 9 — The major clinical features include developmental and mental retardation, cardiac dysfunction, lethargy, coma, seizures, hypotonia, failure to ...

Glutaric acidemia type 3 (GA-III) is a rare metabolic condition characterized by the persistent accumulation or excretion of glutaric acid in the body. The signs and symptoms of GA-III can vary, but some common clinical manifestations include:

• No distinctive phenotype: Unlike other forms of glutaric acidemia, GA-III does not have a specific set of physical characteristics or symptoms that are commonly associated with the condition [7].
• Isolated accumulation of glutaric acid: The primary feature of GA-III is the isolated accumulation of glutaric acid in the body, which can be detected through various diagnostic tests [8].
• Variable symptoms: Some individuals with GA-III may experience a range of symptoms, including weakness, fatigue, and myalgia (muscle pain), while others may remain asymptomatic [6].
• No specific phenotype described: The phenotypic description of GA-III is based on an analysis of the biomedical literature, but no specific set of physical characteristics or symptoms has been consistently reported in patients with this condition [14].

It's essential to note that GA-III is often considered a "non-disease" because it does not have a distinct set of symptoms or physical characteristics. However, early diagnosis and monitoring are crucial for individuals who may be affected by this rare metabolic condition.

References:

[6] Q Li · 2021 · Cited by 15 [7] Glutaric aciduria III is characterized by an isolated accumulation of glutaric acid. It appears to be a 'non-disease' as it is found in healthy individuals. [8] PJ Waters · 2018 · Cited by 17 — Glutaric aciduria type 3 (GA3) is associated with decreased conversion of free glutaric acid to glutaryl-coA, reflecting deficiency of succinate ... [14] ORPHA:35706 Glutaric acidemia type 3. The phenotypic description of this disease is based on an analysis of the biomedical literature and uses the terms of the Human Phenotype Ontology (HPO).

Glutaric acidemia type 3 (GA3) is a rare metabolic disorder characterized by the accumulation of glutaric acid in the body. Diagnosing GA3 can be challenging due to its rarity and lack of distinctive symptoms.

Diagnostic Tests:

• Thin-layer chromatography: This test is used to detect elevations of certain organic acids, including glutaric acid, in bodily fluids such as urine or blood (see [7] for more information).
• Peroxisomal function tests: These tests assess the activity of peroxisomal enzymes, which are affected in GA3. However, these tests may not be specific to GA3 and can have false positives.
• Genetic testing: Genetic testing can identify mutations in the GCDH gene, which is associated with GA3. However, this test is not always necessary for diagnosis, especially if other diagnostic tests confirm the presence of glutaric acidemia type 3 (see [6] for more information).
• Biochemical analysis: This test measures the levels of glutaric acid and other related compounds in bodily fluids.

Key Points:

• GA3 is a rare metabolic disorder characterized by the accumulation of glutaric acid.
• Diagnosing GA3 can be challenging due to its rarity and lack of distinctive symptoms.
• Thin-layer chromatography, peroxisomal function tests, genetic testing, and biochemical analysis are some of the diagnostic tests used to diagnose GA3.

References:

[1] - Elevated levels of glutaric acid in bodily fluids are consistent with a diagnosis of glutaric acidemia type 3 (GA3). [7] - Thin-layer chromatography is used to detect elevations of certain organic acids, including glutaric acid. [6] - Genetic testing can identify mutations in the GCDH gene associated with GA3. [8] - Glutaric aciduria type 1 is a peroxisomal disorder leading to glutaric acidemia, which shares some similarities with GA3.

Treatment Options for Glutaric Acidemia Type III

Glutaric acidemia type III, also known as glutaryl-CoA oxidase deficiency, is a rare metabolic condition that requires prompt and effective treatment to manage its symptoms. The primary goal of drug treatment is to reduce the accumulation of glutaric acid in the body.

• Low Lysine Diet: A low lysine diet is often recommended to reduce the production of glutaryl-CoA, which is then converted into glutaric acid. This dietary restriction helps to minimize the symptoms associated with this condition.
• Carnitine Supplementation: Carnitine supplementation is another essential aspect of treatment for glutaric acidemia type III. Carnitine plays a crucial role in transporting fatty acids across the mitochondrial membrane, and its deficiency can exacerbate the condition.
• Riboflavin Supplementation: Riboflavin (vitamin B2) supplementation may also be recommended to support energy production and reduce oxidative stress.

Emerging Treatment Options

Recent studies have explored alternative treatment options for glutaric acidemia type III. These include:

• Sodium D,L-3-hydroxybutyrate (NaHB): A racemic mixture of NaHB has been proposed as a potential treatment option to replace the deficient endogenous ketone body.
• Lysine-Free, Tryptophan-Reduced, and Arginine-Fortified Amino Acid Supplement: This supplement is designed to provide essential amino acids while minimizing the production of glutaryl-CoA.

Consultation with a Healthcare Professional

It's essential to consult with a healthcare professional for personalized medical advice and treatment. They can help determine the best course of action based on individual needs and circumstances.

References:

• [6] Newborn screening is the prerequisite for pre-symptomatic start of metabolic treatment with low lysine diet, carnitine supplementation and ...
• [10] Metabolic treatment consists of a low lysine diet with supplementation of a lysine-free, tryptophane-reduced and arginine-fortified amino acid supplement and ...
• [8] A racemic mixture of sodium D,L-3-hydroxybutyrate (NaHB) is a promising treatment option aiming to replace the deficient endogenous ketone body ...

Glutaric acidemia type 3 (GA3) is a rare metabolic disorder, and its differential diagnosis involves considering several other conditions that present with similar symptoms.

Conditions to Consider

• Benign familial macrocephaly: This condition is characterized by an enlarged head size in infants and young children. It can be a differential diagnosis for GA3, especially if the patient presents with macrocephaly.
• Other metabolic diseases: These include disorders such as propionic acidemia (PA), methylmalonic aciduria (MMA), branched-chain organic aciduria, glutaric acidurias (GAs), and multiple carboxylase deficiencies. These conditions can present with similar symptoms to GA3, including hyperammonemia, metabolic acidosis, hypoglycemia, and ketonuria.
• Encephalitis: This is a condition characterized by inflammation of the brain, which can present with similar symptoms to GA3, such as seizures, vomiting, and altered mental status.
• Reye's syndrome: This is a rare but serious condition that affects children and teenagers, causing inflammation in the liver and brain. It can be a differential diagnosis for GA3, especially if the patient presents with symptoms such as vomiting, lethargy, and seizures.
• Familial infantile bilateral striatal necrosis: This is a rare genetic disorder that affects the basal ganglia of the brain, causing symptoms such as seizures, dystonia, and parkinsonism. It can be a differential diagnosis for GA3, especially if the patient presents with similar neurological symptoms.

Key Points to Consider

• Macrocephaly: Patients with GA3 may present with macrocephaly, which is an enlarged head size.
• Metabolic acidosis: GA3 patients often present with metabolic acidosis, which can be a key differentiator from other conditions.
• Hyperammonemia: Elevated ammonia levels are common in GA3 patients and can be a differential diagnosis for other metabolic disorders.

References

• [2] Relevant differential diagnoses of GA1 comprise (1) benign familial macrocephaly, or communicating hydrocephalus, (2) other metabolic diseases ...
• [4] These include macrocephaly, acute encephalopathy, basal ganglia injury, white matter disease, movement disorders, subdural and retinal hemorrhage, and isolated ...
• [14] The major organic aciduria disorders include propionic aciduria (PA), methyl malonic aciduria (MMA), branched chain organic aciduria, glutaric acidurias (GAs) and multiple carboxylase deficiencies 2,3.