2-aminoadipic 2-oxoadipic aciduria

What is 2-Aminoadipic 2-Oxoadipic Aciduria?

2-Aminoadipic 2-oxoadipic aciduria, also known as AAKAD or AMOXAD, is a rare genetic disorder that affects the metabolism of lysine and tryptophan. This condition is characterized by an accumulation of specific compounds in the urine and blood, leading to various clinical symptoms.

Key Features:

• Metabolic Disorder: 2-Aminoadipic 2-oxoadipic aciduria is a metabolic disorder that affects the breakdown and utilization of lysine and tryptophan.
• Accumulation of Compounds: The condition leads to an accumulation of 2-oxoadipate, 2-hydroxyadipate, and 2-aminoadipate in the urine and blood.
• Variable Clinical Presentation: Patients with this disorder may exhibit a range of clinical symptoms, including:
  • Hypotonia (low muscle tone)
  • Developmental delay
  • Mild to severe intellectual disability
  • Ataxia (loss of coordination)
  • Epilepsy
  • Behavioral disorders, such as attention deficit hyperactivity disorder (ADHD)

Causes and Genetics:

• Genetic Mutations: 2-Aminoadipic 2-oxoadipic aciduria is caused by genetic mutations that affect the metabolism of lysine and tryptophan.
• Hereditary and Random Mutations: These mutations can be inherited from parents or occur randomly during cell division.

References:

• [1] Uniprot Description
• [2] Monarch Initiative
• [3] Various medical articles and research papers (cited in the context)

Signs and Symptoms of 2-Aminoadipic 2-Oxoadipic Aciduria

2-Aminoadipic 2-oxoadipic aciduria is a rare metabolic disorder characterized by high levels of compounds known as 2-oxoadipate and 2-hydroxyadipate in the urine, and elevated levels of the compound 2-aminoadipate in the blood. The signs and symptoms of this condition can vary widely among individuals.

• Variable clinical presentation: Some people with 2-aminoadipic 2-oxoadipic aciduria may not show any symptoms (asymptomatic), while others may experience a range of symptoms, including:
  • Hypotonia (muscular weakness)
  • Developmental delay
  • Mild to severe intellectual disability
  • Ataxia (loss of coordination and balance)
  • Epilepsy
  • Behavioral disorders, most commonly attention deficit hyperactivity disorder (ADHD) [1][6][10][12]
• Asymptomatic cases: Over half of people who have this condition do not show any symptoms, making it difficult to diagnose. [1]

It's essential to note that the severity and presentation of symptoms can vary widely among individuals with 2-aminoadipic 2-oxoadipic aciduria.

References:

[1] Context result 1: "Over half of people who have this condition do not show any symptoms (asymptomatic)."

[6] Context result 6: "variable clinical presentation including hypotonia, developmental delay, mild to severe intellectual disability, ataxia, epilepsy and behavioral disorders, most commonly attention deficit hyperactivity disorder."

[10] Context result 10: "2-aminoadipic 2-oxoadipic aciduria is a rare disorder of lysine and hydroxylysine metabolism characterized by variable clinical presentation including hypotonia, developmental delay, mild to severe intellectual disability, ataxia, epilepsy and behavioral disorders, most commonly attention deficit hyperactivity disorder."

[12] Context result 12: "Patients can have mild to severe intellectual disability, muscular hypotonia, developmental delay, ataxia, and epilepsy."

Diagnostic Tests for 2-Aminoadipic 2-Oxoadipic Aciduria

2-Aminoadipic 2-oxoadipic aciduria is a rare metabolic disorder that can be diagnosed using various diagnostic tests. Here are some of the diagnostic tests used to diagnose this condition:

• Blood and Urine Tests: These tests can detect high levels of compounds known as 2-oxoadipate and 2-hydroxyadipate in the urine, and elevated levels of the compound 2-aminoadipate in the blood [6][11].
• Exome Sequencing: This test can confirm diagnosis by identifying mutations responsible for 2-aminoadipic and 2-oxoadipic aciduria in individual patients [7][9].
• Gas Chromatography-Mass Spectrometry (GC-MS): This test is used to detect the presence of specific metabolites in the urine, such as 2-oxoisocaproic acid and 2-hydroxyglutaric acid [12].

Clinical Genetic Tests

There are also clinical genetic tests available for diagnosing 2-aminoadipic 2-oxoadipic aciduria. These tests include:

• Intergen Clinical Genetic Test: This test is offered by Intergen and includes testing for the DHTKD1 gene [4].
• Quest Diagnostics Nichols Institute San Juan Capistrano Clinical Genetic Test: This test is offered by Quest Diagnostics Nichols Institute San Juan Capistrano and includes testing for conditions such as 2-aminoadipic 2-oxoadipic aciduria, propionic acidemia, and 2-hydroxyglutaric aciduria [12].

Diagnostic Teams

A diagnostic team for 2-aminoadipic 2-oxoadipic aciduria may include:

• Genetics: A geneticist can help diagnose the condition by identifying mutations responsible for the disorder [10][11].
• Metabolic Specialists: Metabolic specialists can also be involved in diagnosing and managing this condition.

References: [4] Clinical Genetic Test offered by Intergen [6] Blood and Urine Tests [7] Exome Sequencing [9] Exome sequencing can confirm diagnosis by identifying mutations responsible for 2-aminoadipic and 2-oxoadipic aciduria in individual patients [10] Diagnostic teams for 2-aminoadipic 2-oxoadipic aciduria may include: Genetics. [11] 2-Aminoadipic 2-Oxoadipic Aciduria is a rare metabolic disorder characterised by high levels of compounds known as 2-oxoadipate and 2-hydroxyadipate in the urine, and elevated levels of the compound 2-aminoadipate in the blood. [12] Clinical Genetic Test offered by Quest Diagnostics Nichols Institute San Juan Capistrano

Current Understanding of Drug Treatment for 2-Aminoadipic 2-Oxoadipic Aciduria

While there is no specific treatment or cure for 2-aminoadipic 2-oxoadipic aciduria, research has been conducted to explore potential therapeutic options. According to the available information [10][13], a substrate reduction therapy for the treatment of glutaric aciduria type I (GA1) by inhibition of DHTKD1 was evaluated.

Pharmacologic Inhibition of DHTKD1

Studies have shown that pharmacologic inhibition of DHTKD1 might be an interesting new drug target for GA1, as it converts this disease into 2-aminoadipate and 2-oxoadipate [7]. This suggests a potential therapeutic approach for 2-aminoadipic 2-oxoadipic aciduria.

Targeting the LKR Domain

Research has also highlighted the significance of saccharopine degradation in neurodevelopment, and targeting the LKR domain may hold promise as a potential treatment [9].

Current Treatment Guidelines

While specific treatment guidelines for 2-aminoadipic 2-oxoadipic aciduria are not well-established, it is essential to consult with a qualified specialist for personalized care and management of symptoms.

References:

[7] by K Danhauser · 2012 · Cited by 123 — Pharmacologic inhibition of DHTKD1 might be an interesting new drug target for glutaric aciduria type I in that it converts this disease into 2-aminoadipate and ...

[9] by K Danhauser · 2012 · Cited by 123 — These findings suggest the significance of saccharopine degradation in neurodevelopment, and targeting the LKR domain may hold promise as a potential treatment ...

[10] 2-aminoadipic 2-oxoadipic aciduria is a rare disorder of lysine and hydroxylysine metabolism characterized by variable clinical presentation including hypotonia, developmental delay, mild to severe intellectual disability, ataxia, epilepsy and behavioral disorders, most commonly attention deficit hyperactivity disorder. ... Up-to-date treatment ...

[13] 7 Drug Discovery Institute, Icahn School of Medicine at Mount ... The existence of this complex is based on the identification of mutations in DHTKD1 in individuals with 2-aminoadipic and 2-oxoadipic aciduria (AMOXAD, MIM ... A substrate reduction therapy for treatment of GA1 by inhibition of DHTKD1 was evaluated by knocking out DHTKD1 ...

Differential Diagnosis of 2-Aminoadipic 2-Oxoadipic Aciduria

2-Aminoadipic 2-oxoadipic aciduria is a rare metabolic disorder characterized by high levels of compounds known as 2-oxoadipate and 2-hydroxyadipate in the urine, and elevated levels of the compound 2-aminoadipate in the blood. When diagnosing this condition, it's essential to consider other possible causes that may present with similar symptoms.

Possible Differential Diagnoses:

• Charcot-Marie-Tooth (CMT) disease type 2: This genetic disorder affects the peripheral nerves and can cause muscle weakness, ataxia, and sensory loss. [10]
• Spinal Muscular Atrophy (SMA): A genetic disorder that affects the nerve cells responsible for controlling voluntary muscle movement, leading to muscle weakness and wasting. [5]
• Lipoic acid synthesis defects: These defects can cause a range of symptoms, including muscle weakness, ataxia, and developmental delay. [7]
• Other organic acidemias/acidurias: These are a group of rare genetic disorders that affect the metabolism of certain amino acids, leading to symptoms such as hypotonia, developmental delay, and