Leigh’s Disease: A Look into the Neurological Disease
Summary of Disease
Leigh’s disease is a genetic disorder affecting the nervous system. It normally becomes apparent within the first year of life, with signs and symptoms progressing rapidly.1 It is distinguished by the degeneration of the nervous system, specifically the brain and spinal cord, causing progressive loss of mental and movement abilities. In rare cases, this disease can occur in teenagers and adults.1
Etiology and Pathology
Leigh’s Disease is caused by mutations in mitochondrial or nuclear DNA, resulting in the deficiency of an enzyme present in the body called pyruvate dehydrogenase, which is responsible for regulating metabolism.2 This deficiency is caused by mutations in one or a couple of different disease genes, which are inherited in three different ways.
“Leigh’s Disease is caused by mutations in mitochondrial or nuclear DNA, resulting in the deficiency of an enzyme present in the body called pyruvate dehydrogenase, which is responsible for regulating metabolism.”
There are three different types of Leigh’s Disease, all with different inheritance patterns. One type has an autosomal recessive pattern, meaning that both copies of the responsible gene in each cell have mutations. The parents of someone with an autosomal recessive pattern each carry one copy of the mutated gene, but themselves do not display any symptoms of the disease.3 The second type of Leigh’s disease is inherited maternally, meaning that only mothers carry the mutated gene and can pass it along. In a few affected individuals, Leigh’s disease can also be inherited in an X-linked recessive pattern, meaning that the mutated gene is located on the X-chromosome, one of the two sex chromosomes.4
Symptoms
The earliest signs of Leigh’s disease in infants include diarrhea, vomiting, and difficulty swallowing, ultimately resulting in an inability to gain weight and grow at a normal rate. Other common symptoms in infants include loss of head control, uncontrollable crying, poor sucking ability, and seizures.3 If occurring later in childhood, children may experience difficulty in performing movements, such as walking and running, difficulty articulating words, and even diminishment of intellectual skills previously obtained. As the disease progresses over time, some symptoms may also include weakness, lack of muscle tone, and movement disorders.3 Complications may eventually lead to impairment of kidney, respiratory, and heart function.4 Respiratory problems normally develop later on, such as abnormal breathing patterns and difficulty breathing, as well as issues concerning the heart, such as abnormal enlargement of the heart and overgrowth of the membrane dividing the various heart chambers.3
Diagnosis
Leigh’s Disease can be confirmed by imaging tests. Diagnosis criteria include the presence of progressive neurological disease with motor and intellectual developmental delay, raised lactate concentration in the blood, nervous system tissue changes, as well as characteristic features on brain imaging,5 such as brainstem and basal ganglia lesions.6
Tests aside from brain imaging that may be useful in diagnosing Leigh’s Disease include measuring lactic acid concentrations in body fluids like blood or urine, genetic testing, muscle biopsy, and respiratory chain enzyme studies,4 which is a common diagnostic method used in children with a suspected mitochondrial disease, to see if mutations in a certain gene are causative or not. 7
Prognosis
There is currently no cure for Leigh’s Disease.6 Treatment options vary depending on symptoms present in an individual, as well as the type of Leigh’s disease they have. The most common treatment for Leigh’s Disease is thiamine or vitamin B1, as an inhibitor of thiamine triphosphate could be present in an affected individuals’ blood and urine.3 In patients with a pyruvate dehydrogenase deficiency, a high-fat, low-carbohydrate diet may be recommended,2 and this diet would be monitored by 6 Experimental drugs, such as dichloroacetate (DCA) are also being tested in some clinics6, which inhibits pyruvate dehydrogenase kinase, allowing pyruvate to flow into the mitochondria and promote glucose oxidation. 8
Treatment may require the joint effort of medical specialists, such as cardiologists, neurologists, audiologists, eye specialists, and others needed to effectively plan a child’s treatment. 4
Gayathiri Rajkumar
Works Cited
1. Leigh syndrome. MedlinePlus. https://medlineplus.gov/genetics/condition/leigh-syndrome/. Published September 8, 2020. Accessed May 2, 2021.
2. Leigh's Disease Information Page. National Institute of Neurological Disorders and Stroke.
https://www.ninds.nih.gov/Disorders/All-Disorders/Leighs-Disease-Information-Page3. Leigh Syndrome. NORD (National Organization for Rare Disorders). https://rarediseases.org/rare-diseases/leigh-syndrome/. Published August 1, 2017. Accessed May 2, 2021.
4. Leigh syndrome. Genetic and Rare Diseases Information Center. https://rarediseases.info.nih.gov/diseases/6877/leigh-syndrome. Accessed May 2, 2021.
5. Thomas DL. Leigh's Syndrome Diagnosis. News-Medical. https://www.news-medical.net/health/Leighs-Syndrome-Diagnosis.aspx. Published February 27, 2019. Accessed May 2, 2021.
6. Leigh Disease or syndrome. UMDF. https://www.umdf.org/mitochondrial-disease-types/leigh-disease-or-syndrome. Accessed May 2, 2021.
7. Arii J, Tanabe Y. Leigh Syndrome: Serial MR Imaging and Clinical Follow-up. American Journal of Neuroradiology. http://www.ajnr.org/content/21/8/1502. Published September 1, 2000. Accessed May 2, 2021.
8. Mito - Respiratory chain enzymes. VCGS. https://www.vcgs.org.au/order/tests/663. Accessed May 2, 2021.
9. Michelakis ED, Webster L, Mackey JR. Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer. British journal of cancer. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567082/. Published October 7, 2008. Accessed May 2, 2021.
Cite This Article:
Rajkumar G., Vytlingam K., Kozak A., Chharawala V., Ananthakrishnan O., Lombo L. Leigh’s Disease: A Look Into the Neurological Disease. Illustrated by V. Chharawala. Rare Disease Review. February 2022. DOI:10.13140/RG.2.2.18699.98088.
