Tuesday, Oct 21, 2014 | 08:41 AM

Madisons Foundation - Moms And Dads In Search Of Needed Support

Leigh Disease
Sunday, 08 August 2004
Sunday, 08 August 2004
Subacute Necrotizing Encephalomyopathy

What

Leigh Disease is a rare, inherited, neurometabolic (affects the metabolism or internal workings of nerve cells) disorder. It most commonly occurs in children and is characterized by rapid, progressive break down of the function of the central nervous system (the brain and the spinal cord). This rapid break down of function is due to problems in the mitochondria. Mitochondria are tiny structures that act as the “powerhouse” in every cell in the body; they are the energy producing part of the cell. The mitochondria has enzymes that work together in a system called the electron transport chain, converting food and oxygen into the energy needed to fuel the cell’s functions and the body’s normal processes. In Leigh’s Disease, these enzymes in the mitochondria are either missing or do not work correctly.

Who

Leigh Disease typically affects children between 3 months and 2 years of age. However, in some rare cases the onset of the disease may be delayed until adolescence or adulthood. It occurs more commonly in males than in females and the reason for this is not known. Leigh Disease can affect people from all ethnic backgrounds.

Signs and Symptoms

Children with Leigh Disease may have the following features:

  • Feeding problems
  • Loss of appetite
  • Vomiting
  • Failure to thrive (a condition in which weight gain and growth are far below normal)
  • Irritability/continuous crying
  • Delayed motor and language milestones
  • Seizures
  • Generalized Weakness
  • Decreases muscle tone
  • Tremor
  • Problems with muscle coordination
  • Abnormal eye movements
  • Droopy eyelids
  • Vision problems
  • Respiratory and kidney problems (due to presence of lactic acid in the blood)
  • Heart problems

Possible Causes

Leigh Disease is a problem of the mitochondria. It is caused by defects in the enzymes of the mitochondrial electron transport chain. The electron transport chain is responsible for producing the energy our body needs to function properly. Two of the enzymes that are most commonly involved with this disease are called pyruvate dehydrogenase complex and cytochrome-c-oxidase. These enzymes do not work correctly because they are made from genes that carry a change (mutation). These changes can be inherited from the child’s parents or occur spontaneously only in the child. There are 3 ways in which Leigh Disease is inherited: 1. X-linked inheritance: Boys can inherit the disease from a mother who carries a mutated gene. Girls may inherit the carrier status. Males have one X and one Y chromosome and females have two X chromosomes. If males have a gene with a change on their X chromosome they will have the disease. If females have a gene with a change on their X chromosome they have another copy of the gene on their other X chromosome that is functioning normally and this will, “protect” them. 2. Autosomal recessive inheritance: In this case, a child needs two genes with a change to have the disease. Disease occurs when both parents have one copy of a gene with a change and they both pass that gene to their child. 3. Mutation of the Mitochondrial DNA: Mitochondria have their own DNA and mitochondria come only from the mother. In this case, if the mother is affected, all of her children are at risk of inheriting the disease.

Diagnosis

A diagnosis of Leigh Disease is made based on the presence of the above described signs and symptoms, laboratory testing and abnormal results on CT (computed tomography) or MRI (magnetic resonance imaging) scans. These scans provide visual images of structures inside the body. Scans of children with Leigh Disease reveal the changes in the brain that occur as nerve cells die. Genetic tests may be done to try and find the changes in the genes associated with this disease.

Treatment

There is no cure for Leigh Disease, however there are treatment options that can relieve some of the associated symptoms. The treatment is limited and only partially effective. The most common treatment is the administration of thiamine (a vitamin) and vitamin B1. Certain changes in diet may be recommended. Sodium bicarbonate and sodium citrate may be given to treat the lactic acidosis. Sedatives and pain killers may also be prescribed to provide relief from symptoms. Other drug treatments may be needed to treat the seizures, movement problems, and cardiac complications.

Prognosis

The overall outlook for children with Leigh Disease is poor, but a few patients experience prolonged periods of remission. Leigh’s disease usually progress rapidly once the first signs and symptoms appear. Unfortunately, death usually occurs by 6 or 7 years of age, although a few children have survived into their teens.

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

United Mitochondrial Disease Foundation
This site contains general information on mitochondrial diseases, current research, events and activities, online support groups, and local area resources.

CLIMB (Children Living with Inherited Metabolic Diseases)
UK based website featuring information and support services.

NIH/NINDS Brain Resources and Information Network
This site contains information on Leigh Disease, and links to other resources.

Google Search for Leigh Disease

References and Sources

1. Behrman, R (2004), Nelson Textbook of Pediatrics 17th Ed., p.2027 2. Tsao, C (Jan 2003), Leigh Disease with mitochondrial DNA mutation: case report and brief review, J Child Neurol. 18(1):62-64 3. www.ninds.nih.gov/health_and_medical/disorders/leighsdisease_doc.htm