D-2 Hydroxyglutaric Aciduria
What else is it called?
- D-2-hydroxyglutaric acidemia
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What causes it?
D-2-hydroxyglutaric aciduria is a condition that causes progressive damage to the brain. It is one of the main 2-hydroxyglutaric aciduria disorders along with L-2 Hydroxglutaric Aciduria. All of the subtype disorders profoundly and specifically affect development and functioning of the central nervous system.
The different types of 2-hydroxyglutaric aciduria disorders are caused by different genes. Moreover, the D-2-hydroxyglutaric aciduria version has two subtypes, D-2-hydroxyglutaric aciduria type I and D-2-hydroxyglutaric aciduria type II, where the first type is caused by a problem in the D2HGDH gene, and the second type is caused by the problem in the IDH2 gene.
The D2HGDH gene produces the enzyme required within the mitochondria of cells, which are known as the energy producing centres of cells. This condition, in particular, affects one area of the brain called the cerebrum which is involved in coordinating muscle movement, thinking, speech and vision.
The IDH2 gene under normal circumstances also produces the enzyme required within the mitochondria of cells. However, if there is a mutation in this gene, it produces different compound instead, which becomes toxic and damage brain cells.
How common is it?
D-2-hydroxyglutaric aciduria is a rare metabolic condition with fewer than 150 cases being reported worldwide. Due to the rarity of this condition, it is difficult to suggest whether this condition predominates more common in males or females or geographically.
What are the signs and symptoms?
Signs and symptoms for this condition may vary person to person, with some experiencing no symptoms at all [asymptomatic] some of the more common signs and symptoms experienced are:
- Delayed development
- Weakened muscle tone [hypotonia]
- Abnormalities in the largest part of the brain (the cerebrum) that may affect:
- Muscle movement
How is it diagnosed?
This disorder can be characterised biochemically by elevated D-2-hydroxyglutaric acid (D-2-HG) in the urine, plasma and cerebrospinal fluid. These samples therefore are either taken via urine collection, blood test or via lumbar puncture. MRI findings also help to diagnose this condition due to the part of the brain which is affected such as delayed cerebral maturation.
A lumbar puncture involves a thin needle being inserted between the bones in your lower spine to drain some of the cerebrospinal fluid to test for elevated metabolite levels. It shouldn’t be painful, but you may have a headache and some back pain for a few days.
Antenatal diagnosis through gene testing has also become possible for this condition if this is already present within your family history.
Can it be treated?
To date there is no specific treatment for this condition, treatment is solely aimed at managing the symptoms experienced by the individual such as the control of seizures for example.
Do my family need to be tested?
D-2-Hydroxyglutaric aciduria type I can only be passed on to a child if both parents have a copy of the faulty gene. This is called autosomal recessive inheritance. A person who has a copy of the faulty gene is known as a carrier.
If both parents are carriers, their child has a one in four (25%) chance of inheriting the disorder, and a one in two chance (50%) of being a carrier. This is the same for each child the parents have.
D-2-HGA type II is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. The disorder typically results from a new mutation in the IDH2 gene and occurs in people with no history of the condition in their family.
One mutated copy of the gene in each cell is sufficient for a person to be affected by an autosomal dominant disorder. In some cases, an affected person inherits the condition from an affected parent. In others, the condition may result from a new mutation in the gene and occur in people with no history of the disorder in their family.
If the child only inherits one copy of the faulty gene, they will be a carrier but will not have the disorder. In some rare cases, carriers have had mild symptoms of the disorder for which they carry the faulty gene.
Once you are diagnosed, you can speak to a genetic counsellor. They can explain how you may have inherited D-2-Hydroxyglutaric aciduria. They can also tell you about genetic testing for the rest of your family. They can provide advice and support if you go on to have children of your own. If you have previously had a child with D-2-Hydroxyglutaric aciduria and go on to have further children, their New-born Screening test should be carried out within 24-48 hours of birth.
References are available on request. Please contact us by phoning 0845 241 2173 or emailing firstname.lastname@example.org [Resource Library No: AAP002].