L-2 Hydroxyglutaric Aciduria

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This disorder is caused by mutations in the L2HGDH gene. This gene makes an enzyme found in mitochondria which breaks down a compound in order to produce energy. Mutations cause a shortage in this enzyme, allowing the compound to build up. This can damage and destroy cells, with brain cells appearing to be the most vulnerable to this.

This condition had been reported in fewer than 150 individuals with no higher prevalence reported in either sex or any specific ethnicity.

One of three major types of 2-hydroxyglutaric aciduria, a condition causing progressive brain damage. Another type, D-2- hydroxyglutaric aciduria, affects muscle movement, speech, vision, emotion, thinking and memory. The third type is combined D,L-2- hydroxyglutaric aciduria, causing severe abnormalities. Those with the combined type rarely survive past early childhood.

So far, D2 form is associated with more of Grey matter involvement and other system involvement. From our knowledge, currently we think L-2 HGA affects white matter more than grey matter.

L-2-hydroxyglutaric aciduria symptoms are progressive brain damage, developmental delay, speech difficulties, seizures and macrocephaly (an enlarged skull). Problems with balance and muscle coordination are also common. By early adulthood, those with this condition will have severe disability.

Diagnosis may be determined by the acknowledgement of physical symptoms, a patient and family history, and a range of specialised tests including blood and urine analysis and brain MRI or CT scans. Genetic testing can confirm diagnosis.

There is no cure for this disorder. Treatment is currently based on alleviating and managing the individual symptoms which are present, avoiding complications, improving nutrition, limiting progression, and providing support for your child and your family as a whole.

Prognosis is poor, but most people with L-2 Hydroxyglutaric Aciduria reach adulthood.

Humans have chromosomes composed of DNA. Genes are pieces of DNA that carry the genetic instruction. Each chromosome may have several thousand genes.

The word mutation means a change or error in the genetic instruction.

We inherit particular chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instruction that determines characteristics, which are a combination of the parents.

This is an inherited condition. There is nothing that could have been done to prevent your baby from having this condition.

Everyone has a pair of L2HGDH genes. In children with this disorder, neither of these genes works correctly. These children inherit one non-working gene from each parent.

Parents of children with this disorder are termed as carriers of the condition. Carriers do not have the disorder because the other gene of this pair is working correctly. This disorder is autosomal recessive.

When both parents are carriers, in each pregnancy the risk to the baby is as follows:

• There is a 25% chance (1 in 4) of the baby having the disorder.
• There is a 50% chance (1 in 2) for the baby to be a carrier of the disorder.
• There is a 25% chance (1 in 4) for the baby to have two working genes and neither have the disorder nor be a carrier

Established in 2004, Alex TLC provides support for all those with a genetic leukodystrophy and are also an internationally recognised centre of excellence for those affected with adrenoleukodystrophy and adrenomyeloneuropathy.

Alex TLC Contact Details:

• Phone 020 7701 4388
• Email info@alextlc.org
• Website https://www.alextlc.org/

References are available on request. Please contact us on 0800 652 3181 or by emailing contact@metabolicsupport.org.

Please note calls to 0800 numbers are free from UK landlines and mobiles. Calls from business lines may be charged – please check with your provider.

This information about metabolic diseases is provided by Metabolic Support UK and is intended for educational purposes only. It should not be used for diagnostic or treatment purposes.

Should you require more detailed information please contact Metabolic Support UK by email (contact@metabolicsupport.org) or by telephone ( 0800 652 3181). For specific medical information regarding a disorder or individual please contact your GP or Paediatrician. Metabolic Support UK accepts no responsibility for any errors or omissions nor does Metabolic Support UK assume any liability of any kind for the content of any information contained within this summary or any use that you may make of it.