"L-2-Hydroxyglutaric Aciduria" – What Is It?
L-2-hydroxyglutaric aciduria (L2HGA) is a metabolic disorder that affects the nervous system. It is caused by mutations, i.e., genetic changes in the L2HGDH gene. It is characterized by coordination disorders caused by cerebellar damage, developmental delay, epilepsy, and an above-average head circumference of varying degrees.
How Is "L-2-Hydroxyglutaric Aciduria" Diagnosed?
Laboratory Chemical Diagnostics
Screening for organic acids reveals massively elevated levels of L-2-hydroxyglutaric acid in urine, blood, and cerebrospinal fluid. Further laboratory tests can then confirm the diagnosis of L2HGA biochemically.
Imaging Diagnostics
CT and MRI of the head show a constellation of findings typical of L2HGA, including a reduced cerebellum size.
Genetic Diagnostics
The diagnosis of “L-2-hydroxyglutaric aciduria” is considered confirmed if a mutation, i.e., genetic change, is detected in the L2HGDH gene.
What Is the Risk of Cancer?
Patients with L-2-hydroxyglutaric aciduria have an increased risk of various brain tumors (ependymomas, primitive neuroectodermal tumors, low- and high-grade gliomas, medulloblastomas and oligodendrogliomas). However, it is not yet possible to quantify precisely how high the risk is.
Clinically, L2HGA usually manifests itself within the first year of life through developmental delay, epileptic seizures, or coordination disorders. Around half of patients have an above-average head circumference. Other symptoms include muscular weakness, usually at an earlier stage of the disease, movement disorders, behavioral problems, and spasticity (muscle cramps), which tend to occur later in the course of the disease. Overall, the disease progresses slowly, and most sufferers reach adulthood. However, complete loss of motor skills (e.g., loss of the ability to walk) and speech problems can occur in the course of the disease.
Regarding laboratory chemistry, L2HGA is characterized by high levels of L-2-hydroxyglutaric acid in the urine, blood, and cerebrospinal fluid.
What Is Known About the Development of "L-2-Hydroxyglutaric Aciduria"?
L-2-hydroxyglutaric aciduria is caused by mutations, i.e., genetic changes in the L2HGDH gene. This gene codes for the protein L-2-hydroxyglutarate dehydrogenase, which is involved in metabolic processes in the brain, among other things.
If the L2HGDH gene is present in an altered form, the corresponding protein is also not produced correctly and can no longer fulfill its actual function. This leads to an accumulation of L-2-hydroxyglutaric acid and, thus, to brain damage.
L2HGA is a rare disease with an incidence of 1:1,000,000 and can be passed on from parents to their children. The inheritance is autosomal recessive, so the disease occurs significantly more frequently in children of blood-related parents than in the general population.
Is There Any Form of Treatment Available?
To date, no causative therapy is known, so treatment is limited to supportive, symptom-oriented therapy.
Diagnosis of " L-2-Hydroxyglutaric Aciduria" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Diagnosis of " L-2-Hydroxyglutaric Aciduria" What's Next?
If you have been diagnosed with this cancer predisposition syndrome, it is important to see a specialist. The following section explains whether cancer screening tests or other measures are needed and how they should be carried out. We also give you some valuable tips on what you can do yourself. If you have any questions, please do not hesitate to contact us or your doctor.
Medical Measures for Early Detection
Given the increased risk of brain tumors, a clinical and neurological examination should be carried out every 3-6 months. In addition, an annual MRI of the head is recommended (initially with a contrast medium, then without a contrast medium as long as no abnormalities are found).
L-2-Hydroxyglutaric Aciduria- What You Can Do Yourself
You Should Pay Attention to This
You should consult a doctor as soon as changes in movement or coordination, speech disorders, or epileptic seizures occur. Delays in development should also be noted and reported to a doctor. You should also consult a doctor if you notice any new abnormalities or complaints, such as headaches, nausea, or dizziness.
Further Information
Patients can also register for the CPS registry at any time or have this done by the doctors looking after them.
Any further questions?
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