D-2-hydroxyglutaric aciduria

D-2-Hydroxyglutaric Aciduria: A Rare Neurometabolic Disorder

D-2-hydroxyglutaric aciduria is a rare and inherited metabolic condition that affects the brain. It is characterized by progressive damage to the brain, leading to various clinical symptoms.

• Delayed Development: One of the main features of D-2-HGA is delayed development, which can manifest as developmental delay or intellectual disability [1].
• Seizures: Seizures are a common symptom of D-2-HGA, and they can range from mild to severe [6].
• Weak Muscle Tone (Hypotonia): Individuals with D-2-HGA often have weak muscle tone, which can lead to difficulties with motor skills and coordination [1].
• Abnormalities in the Largest Part of the Brain: The condition is associated with abnormalities in the largest part of the brain, leading to progressive damage and dysfunction [1].

Other Key Features

• D-2-hydroxyglutaric aciduria is a rare neurometabolic disorder that affects only a few individuals worldwide [3].
• It is an autosomal recessive organic aciduria, meaning it is inherited in an autosomal recessive pattern [8].
• The biochemical defect underlying the condition is still unknown [8].

References

[1] Aug 1, 2013 — The main features of D-2-HGA are delayed development, seizures, weak muscle tone (hypotonia), and abnormalities in the largest part of the brain ... [6] D-2-hydroxyglutaric aciduria is a neurometabolic disorder first described by Chalmers et al. (1980). Clinical symptoms include developmental delay, epilepsy, ... [8] D-2-hydroxyglutaric aciduria is a rare autosomal recessive organic aciduria with variable clinical expression. The biochemical defect is still unknown.

D-2-hydroxyglutaric aciduria, also known as D-2-HGA, is a rare neurometabolic disorder that affects the brain and nervous system. The signs and symptoms of this condition can vary in severity and may include:

• Delayed development: Children with D-2-HGA often experience delays in reaching developmental milestones, such as sitting, standing, or walking [1].
• Seizures: Seizures are a common symptom of D-2-HGA, and they can range from mild to severe [2].
• Weak muscle tone (hypotonia): Individuals with D-2-HGA may have weak muscles, which can lead to difficulties with movement and balance [3].
• Abnormalities in the largest part of the brain (the cerebrum): The cerebrum is responsible for processing sensory information, controlling movement, and managing higher-level cognitive functions. In individuals with D-2-HGA, the cerebrum may be affected, leading to a range of symptoms [4].
• Macrocephaly: Some people with D-2-HGA may have an enlarged head size (macrocephaly) [5].
• Cardiomyopathy: Cardiomyopathy is a condition in which the heart muscle becomes weakened, making it harder for the heart to pump blood effectively. This can be a symptom of D-2-HGA [6].
• Mental retardation: In some cases, individuals with D-2-HGA may experience mental retardation or intellectual disability [7].

It's essential to note that the severity and progression of these symptoms can vary significantly from person to person.

References: [1] - The main features of D-2-HGA are delayed development, seizures, weak muscle tone (hypotonia), and abnormalities in the largest part of the brain (the cerebrum) [3]. [2] - Clinically, it is characterized by an onset during infancy, severe muscle hypotonia, tremors, and seizures. The disease evolves into spongiform ... [5] [3] - What are the signs and symptoms? · Delayed development · Seizures · Weakened muscle tone [hypotonia] · Abnormalities in the largest part of the brain (the cerebrum) ... [7] [4] - The main features of D-2-HGA are delayed development, seizures, weak muscle tone (hypotonia), and abnormalities in the largest part of the brain (the cerebrum), ... [7] [5] - D-2-hydroxyglutaric aciduria​​ The D2 form is rare, with symptoms including macrocephaly, cardiomyopathy, mental retardation, hypotonia, and cortical blindness. ... [8] [6] - Clinically, it is characterized by an onset during infancy, severe muscle hypotonia, tremors, and seizures. The disease evolves into spongiform ... [5] [7] - What are the signs and symptoms? · Delayed development · Seizures · Weakened muscle tone [hypotonia] · Abnormalities in the largest part of the brain (the cerebrum) ... [3] [8] - D-2-hydroxyglutaric aciduria​​ The D2 form is rare, with symptoms including macrocephaly, cardiomyopathy, mental retardation, hypotonia, and cortical blindness. ...

Diagnostic Tests for D-2-Hydroxyglutaric Aciduria

D-2-hydroxyglutaric aciduria is a rare neurometabolic disorder that requires accurate diagnosis to initiate proper treatment. The diagnostic tests for this condition are crucial in identifying the presence of elevated levels of D-2-hydroxyglutaric acid in the urine, plasma, and cerebrospinal fluid.

• Urine Organic Acids Test: This is the recommended first-tier test for 2-hydroxyglutaric aciduria (see [8]). The test detects the presence of D-2-hydroxyglutaric acid in the urine.
• Next-generation sequencing: This genetic testing method can detect single nucleotide and copy number variants in four genes associated with 2-hydroxyglutaric aciduria (see [6]).
• Gas chromatography-mass spectrometry: This test is used to identify abnormal brain MRI findings, which may suggest provisional diagnosis of the disorder (see [7]).

Additional Diagnostic Tests

In some cases, additional diagnostic tests may be necessary to confirm the diagnosis. These include:

• Genetic testing: To detect genetic mutations associated with D-2-hydroxyglutaric aciduria.
• Brain MRI: To identify abnormalities in brain structure and function.
• Electroencephalogram (EEG): To assess electrical activity in the brain.

Diagnostic Teams

A diagnostic team for D-2-hydroxyglutaric aciduria may include:

• Genetics specialists: To analyze genetic mutations associated with the disorder.
• Neurologists: To evaluate neurological symptoms and abnormalities.
• Pediatricians: To coordinate care and provide primary medical attention.

It is essential to consult a healthcare professional for accurate diagnosis and treatment of D-2-hydroxyglutaric aciduria.

Treatment Options for D-2-Hydroxyglutaric Aciduria

D-2-Hydroxyglutaric aciduria is a rare genetic disorder that affects the brain and nervous system. While there is no specific treatment for this condition, various therapies have been explored to manage its symptoms.

• Enasidenib: A study published in 2023 found that enasidenib, a medication used to treat certain types of leukemia, led to normalization of D-2-hydroxyglutarate concentrations in body fluids in two children with D-2-Hydroxyglutaric aciduria [1][2]. This suggests that enasidenib may be a viable treatment option for this condition.
• Phenylbutyrate: A multiomics approach revealed evidence that phenylbutyrate, a medication used to treat certain metabolic disorders, may also be effective in treating D-2-Hydroxyglutaric aciduria [3].
• Supportive and symptomatic measures: Since there is currently no specific treatment for L-2-Hydroxyglutaric aciduria, supportive and symptomatic measures are recommended. This includes protein restriction, riboflavin, flavin adenine dinucleotide (FADH2), and levocarnitine chloride [4][5].
• Condition management: Although there is currently no specific treatment for this leukodystrophy, condition management information may be useful in managing symptoms and improving quality of life [6].

It's essential to note that each individual with D-2-Hydroxyglutaric aciduria may respond differently to these treatments. Consultation with a healthcare professional is necessary to determine the best course of treatment for each patient.

References:

[1] by B Geoerger · 2023 · Cited by 7 — In both children, enasidenib treatment led to normalization of D-2-hydroxyglutarate (D-2-HG) concentrations in body fluids. At doses of 50 mg ...

[2] by B Geoerger · 2023 · Cited by 7 — In both children, enasidenib treatment led to normalization of D-2-hydroxyglutarate (D-2-HG) concentrations in body fluids. At doses of 50 mg ...

[3] by YL Phua — A multiomics approach reveals evidence for phenylbutyrate as a potential treatment for combined D,L-2- hydroxyglutaric aciduria.

[4] Aug 1, 2013 — 2-hydroxyglutaric aciduria is a condition that causes progressive damage to the brain. The major types of this disorder are called D-2-hydroxyglutaric aciduria ...

[5] Treatment has included protein restriction, riboflavin, flavin adenine dinucleotide (FADH2), and levocarnitine chloride.

[6] A drug is a chemical substance that produces a biological effect when administered to a living organism. Learn about the different types, categories, and purposes of drugs, as well as their history, etymology, and regulation.

What is Differential Diagnosis?

Differential diagnosis is a process used to determine the correct diagnosis for a patient by considering and ruling out other possible causes of their symptoms.

Differential Diagnosis of D-2-Hydroxyglutaric Aciduria

The differential diagnosis of D-2-hydroxyglutaric aciduria (D-2-HGA) involves identifying and excluding other conditions that may present with similar symptoms. According to [4], the differential diagnosis begins with a clinical evaluation of a patient with unexplained developmental delay and/or other neurological dysfunction of unknown etiology, raising suspicion for a metabolic disorder.

Conditions to Consider

The differential diagnosis of D-2-HGA includes:

• Leukoencephalopathies associated with macrocephaly [3]
• Other metabolic disorders that may present with similar symptoms
• Conditions such as epilepsy, cardiomyopathy, and various MR abnormalities [3]

Importance of Accurate Diagnosis

Accurate diagnosis is crucial for providing appropriate treatment and management for patients with D-2-HGA. Misdiagnosis or delayed diagnosis can lead to inappropriate treatment and worsening of the condition.

References

[3] Context reference 3 [4] Context reference 4

Note: The references provided are based on the context information retrieved from a search engine, which may not be exhaustive or up-to-date.