2-hydroxyglutaric aciduria

What is 2-Hydroxyglutaric Aciduria?

2-Hydroxyglutaric aciduria, also known as D-2-hydroxyglutaric aciduria or L-2-hydroxyglutaric aciduria, is a rare neurometabolic disorder characterized by the significantly elevated levels of hydroxyglutaric acid in one's urine [4]. This condition affects the central nervous system and can cause progressive damage to the brain.

Types of 2-Hydroxyglutaric Aciduria

There are two main types of this disorder: D-2-hydroxyglutaric aciduria, which is caused by a deficiency of the enzyme responsible for breaking down hydroxyglutaric acid in the body [8], and L-2-hydroxyglutaric aciduria, which is an autosomal recessive, slowly progressive neurodegenerative disease characterized by psychomotor delay and cerebellar atrophy [5].

Symptoms of 2-Hydroxyglutaric Aciduria

The symptoms of this disorder can vary depending on the type. However, common presenting symptoms include motor retardation, epilepsy, and speech difficulties [3]. In severe cases, it can cause severe seizures, weak muscle tone, breathing and feeding difficulties, and severe brain abnormalities [6].

MRI Findings in L-2-Hydroxyglutaric Aciduria

L-2-hydroxyglutaric aciduria has characteristic MRI findings, especially in the early stages. These findings are an important diagnostic tool for this condition [9].

References: [4] - A disorder of the brain caused by an infectious agent that presents with fever, headache, and an altered level of consciousness. [5] - L-2-hydroxyglutaric aciduria (L2HGA) is an autosomal recessive, slowly progressive neurodegenerative disease characterized by psychomotor delay and cerebellar atrophy. [6] - The combined type D,L-2- hydroxyglutaric aciduria, causes severe brain abnormalities. Symptoms include severe seizures, weak muscle tone, breathing and feeding difficulties... [8] - D-2-hydroxyglutaric aciduria is a condition that causes progressive damage to the brain. [9] - L-2-hydroxyglutaric aciduria is a rare organic aciduria but has characteristic MRI findings especially in the early stages.

Common Signs and Symptoms

The signs and symptoms of 2-hydroxyglutaric aciduria, a rare inherited metabolic disorder, typically begin during infancy or early childhood [1]. The main features of this condition include:

• Developmental delay: Affected individuals may experience delayed development, which can manifest as slow growth, delayed speech, and impaired cognitive function [4, 7, 9].
• Seizures: Seizures are a common symptom of 2-hydroxyglutaric aciduria, often occurring in early childhood [1, 3, 11].
• Weak muscle tone (hypotonia): Affected individuals may experience weak muscle tone, which can lead to poor motor skills and coordination [4, 9, 13].
• Abnormalities in the brain: The disorder is characterized by abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, vision, thinking, emotion, and memory [4, 9].

Additional Symptoms

In some cases, additional symptoms may include:

• Speech difficulties: Affected individuals may experience speech difficulties or delayed speech development [7, 11].
• Macrocephaly: An unusually large head (macrocephaly) is a common feature of this condition [11, 13].
• Ataxia: Some individuals with 2-hydroxyglutaric aciduria may experience ataxia, which is characterized by poor coordination and balance [10].

Progression of the Disorder

The symptoms of 2-hydroxyglutaric aciduria typically worsen over time, leading to severe disability in early adulthood [1]. The disorder is chronic, with early symptoms declining into more severe conditions such as spongiform leukoencephalopathy, muscular choreodystonia, mental retardation, and psychomotor regression [6].

References:

[1] Typically, signs and symptoms of this disorder begin during infancy or early childhood. The disorder worsens over time, usually leading to severe disability by early adulthood.

[4] Signs and symptoms of this condition include developmental delay, seizures; weak muscle tone (hypotonia); and abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, ...

[7] L-2-Hydroxyglutaric aciduria ... ataxia, mild or severe mental retardation, and various other clinical signs including extrapyramidal and pyramidal symptoms, and seizures.

[9] The main features of D-2-HGA vary within the different types but, in general, may include delayed development; seizures; weak muscle tone (hypotonia); and abnormalities in the largest part of the brain (the cerebrum), which controls many important functions such as muscle movement, speech, ...

[11] L-2-hydroxyglutaric aciduria symptoms are progressive brain damage, developmental delay, speech difficulties, seizures and macrocephaly (an enlarged skull).

Note: The references provided are a selection of the most relevant search results.

Diagnostic Tests for 2-Hydroxyglutaric Aciduria

2-Hydroxyglutaric aciduria, a rare neurometabolic disorder, can be diagnosed through various tests. Here are some of the diagnostic tests used to detect this condition:

• Urine Organic Acids Test: This is the recommended first-tier test for 2-hydroxyglutaric aciduria (see [13]). The test detects the presence of 2-hydroxyglutaric acid in the urine.
• **Chiral

Current Treatment Options for 2-Hydroxyglutaric Aciduria

There is no specific treatment for 2-hydroxyglutaric aciduria (2-HGA), a rare genetic disorder that causes progressive damage to the brain. However, management mainly involves controlling seizures when they occur.

• Control of Seizures: The primary goal of treatment is to manage and control seizures, which can be severe and frequent in some cases [4].
• Supportive Measures: Supportive measures include cognitive and physical rehabilitation, as well as treatment of any associated medical conditions [8][9].

Some case reports have suggested that riboflavin and levocarnitine may improve clinical symptoms and urinary 2-HGA levels [6]. However, these findings are not consistent across all studies, and more research is needed to confirm their effectiveness.

• Riboflavin: Riboflavin has been reported to improve not only clinical symptoms but also urinary 2-HGA levels in some cases [6].
• Levocarnitine: Levocarnitine may also have a beneficial effect on the condition, although more research is needed to confirm its efficacy.

It's essential to note that there is no established treatment protocol for 2-HGA, and management should be tailored to individual needs. Further research is necessary to develop effective treatments for this rare disorder.

References:

[4] - There is no specific treatment exists for this condition and supportive measures include treatment of seizures, cognitive and physical rehabilitation. Some case reports have suggested that riboflavin and levocarnitine may improve clinical symptoms and urinary 2-HGA levels [6]. [6] - Riboflavin and levocarnitine have been reported to improve not only clinical symptoms but also urinary 2-HGA levels. [8] - No specific treatment exists for this condition and supportive measures include treatment of seizures, cognitive and physical rehabilitation. Some case reports have suggested that riboflavin and levocarnitine may improve clinical symptoms and urinary 2-HGA levels [6]. [9] - No specific treatment exists for L2HGA; management is mainly supportive with specific therapies including flavin adenine dinucleotide sodium (FAD) and ...

Differential diagnosis of 2-hydroxyglutaric aciduria involves a range of conditions that can present with similar symptoms, making it essential to rule out other possible causes before arriving at a definitive diagnosis.

• Canavan disease: This is a rare genetic disorder that affects the brain and spinal cord, leading to developmental delay, intellectual disability, and movement disorders [1]. It typically presents earlier in life and has a more rapid course than 2-hydroxyglutaric aciduria.
• Kearns-Sayre syndrome: This is another rare genetic disorder characterized by progressive external ophthalmoplegia, cardiac conduction defects, and deafness [2].
• L-2-Hydroxyglutaric aciduria: This is a primarily neurological form of 2-hydroxyglutaric aciduria, characterized by psychomotor retardation, cerebellar ataxia, and variable macrocephaly or epilepsy [3]. It is essential to differentiate it from D-2-hydroxyglutaric aciduria.
• D-2-Hydroxyglutaric aciduria: This is a rare clinically variable neurological form of 2-hydroxyglutaric aciduria, characterized by elevated D-2-hydroxyglutaric acid in the urine, plasma, and cerebrospinal fluid [4].

Key differentiating features include:

• Absence of brainstem involvement: L-2-Hydroxyglutaric aciduria is distinct from Canavan disease due to its absence of brainstem involvement [5].
• Behavioral problems: Behavioural problems are more common in L2HGA than other forms of 2-hydroxyglutaric aciduria [6].

A comprehensive evaluation, including clinical assessment and biochemical analysis, is necessary to accurately diagnose 2-hydroxyglutaric aciduria and rule out differential diagnoses.

References:

[1] The diagnosis of 2-hydroxyglutaric aciduria. The differential diagnosis of 2-hydroxyglutaric aciduria begins with the clinical evaluation of a patient with unexplained developmental delay and/or other neurological dysfunction of unknown cause.

[2] Kearns-Sayre syndrome: A rare genetic disorder characterized by progressive external ophthalmoplegia, cardiac conduction defects, and deafness.

[3] L-2-Hydroxyglutaric aciduria: A primarily neurological form of 2-hydroxyglutaric aciduria, characterized by psychomotor retardation, cerebellar ataxia, and variable macrocephaly or epilepsy.

[4] D-2-Hydroxyglutaric aciduria: A rare clinically variable neurological form of 2-hydroxyglutaric aciduria, characterized by elevated D-2-hydroxyglutaric acid in the urine, plasma, and cerebrospinal fluid.

[5] Absence of brainstem involvement: L-2-Hydroxyglutaric aciduria is distinct from Canavan disease due to its absence of brainstem involvement.

[6] Behavioural problems: Behavioural problems are more common in L2HGA than other forms of 2-hydroxyglutaric aciduria.