Leigh disease

Leigh Disease: A Rare Genetic Disorder

Leigh disease, also known as Leigh syndrome or subacute necrotizing encephalomyelopathy (SNE), is a rare genetic neurometabolic disorder that affects the central nervous system. It is characterized by progressive loss of mental and movement abilities, leading to severe disability and often death [1].

Causes and Symptoms

Leigh disease is caused by mutations in mitochondrial DNA or deficiencies of an enzyme called pyruvate dehydrogenase [6]. The symptoms of Leigh's disease typically appear in infancy, often after a viral infection, and may include:

• Loss of motor milestones
• Hypotonia with poor head control
• Recurrent vomiting
• Movement disorder
• Pyramidal and extrapyramidal signs (e.g., weakness, stiffness)
• Optic atrophy
• Defects in cognitive function [9]

Characteristics

Leigh syndrome is a mitochondrial disorder that affects the brain, spinal cord, and other parts of the nervous system. It is characterized by progressive degeneration of these tissues, leading to severe disability and often death [3]. The disease can also cause seizures, developmental delays, heart issues, and breathing difficulties [2].

Age of Onset

Leigh syndrome typically becomes apparent in infancy, but it can sometimes affect adults [4]. The age of onset can vary depending on the underlying genetic mutation or enzyme deficiency.

References:

[1] Apr 28, 2023 — This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death ...

[2] This rare mitochondrial disease causes seizures, developmental delays, heart issues and breathing difficulties. It sometimes affects adults.

[3] Leigh syndrome is a rare genetic neurometabolic disorder. It is characterized by the degeneration of the central nervous system (i.e., brain, spinal cord, and ...

[4] Leigh syndrome is a rare, inherited neurodegenerative condition. It usually becomes apparent in infancy, often after a viral infection.

[5] Leigh's disease can be caused by mutations in mitochondrial DNA or by deficiencies of an enzyme called pyruvate dehydrogenase. Symptoms of Leigh's disease ...

[6] Leigh syndrome (or Leigh's disease) is a mitochondrial disorder, sometimes called subacute necrotizing encephalomyelopathy (SNE).

[7] Loss of motor milestones, hypotonia with poor head control, recurrent vomiting, and a movement disorder are common initial symptoms. Pyramidal and ...

[8] Leigh disease is a progressive neurodegenerative disorder with severe hypotonia, seizures, extrapyramidal movement disorder, optic atrophy, and defects in ...

Early Signs and Symptoms

Leigh disease, also known as subacute necrotizing encephalomyelopathy, is a rare mitochondrial disorder that affects the nervous system. The early signs and symptoms of this condition can be quite distressing for both children and adults.

• Poor sucking ability: This is often one of the first signs of Leigh syndrome in infants [3].
• Loss of head control and motor skills: As the condition progresses, individuals may experience a decline in their motor abilities, making it difficult to perform everyday tasks [4][5].
• Loss of appetite: Vomiting and loss of appetite are common symptoms associated with progressive neurological deterioration [2].
• Vomiting: Frequent vomiting is another early sign of Leigh syndrome, which can lead to dehydration and electrolyte imbalances if left untreated [3][5].
• Seizures: Seizures are a common symptom of Leigh disease, especially in infants and young children [1].

Additional Symptoms

As the condition progresses, individuals with Leigh syndrome may experience additional symptoms, including:

• Loss of motor milestones: This can include loss of previously acquired motor skills, making it difficult to perform everyday tasks [2].
• Hypotonia: Weakness or low muscle tone is a common symptom associated with Leigh disease [8].
• Recurrent vomiting: Vomiting can be a persistent problem for individuals with Leigh syndrome, leading to dehydration and electrolyte imbalances if left untreated [8].

Diagnosis

It's often difficult to diagnose Leigh syndrome when symptoms first start, as the early signs and symptoms can be quite non-specific [6]. Early problems may include lack of appropriate weight gain, which can be a red flag for healthcare providers.

References: [1] - This rare mitochondrial disease causes seizures, developmental delays, heart issues and breathing difficulties. It sometimes affects adults. Treatments can ease ... [2] - Symptoms are associated with progressive neurological deterioration and may include loss of previously acquired motor skills, loss of appetite, vomiting, ... [3] - Apr 28, 2023 — The first signs of Leigh syndrome seen in infancy are usually vomiting, diarrhea, and difficulty swallowing (dysphagia), which disrupts eating. [4] - Early symptoms may include poor sucking ability; loss of head control and motor skills; loss of appetite; vomiting; and seizures. As the condition progresses, ... [5] - The earliest signs may be poor sucking ability,and the loss of head control and motor skills.These symptoms may be accompanied by loss of appetite, vomiting, ... [6] - So, it is often difficult to diagnose Leigh syndrome when symptoms first start. Early problems may include: Lack of appropriate weight gain. [7] - Dec 23, 2022 — Symptoms · loss of appetite · continuous crying · frequent vomiting · irritability · seizures · failure to grow or reach developmental ... [8] - Loss of motor milestones, hypotonia with poor head control, recurrent vomiting, and a movement disorder are common initial symptoms. Pyramidal and ...

Based on the context provided, here are some diagnostic tests for Leigh disease:

1. Blood tests: To check for lactic acidosis and enzyme markers that indicate Leigh syndrome.
2. Imaging scans: Such as MRI to check for damaged areas of brain tissue.
3. Skin biopsy: For infants below 3 months old, a skin biopsy can be performed to establish a biochemical and genetic diagnosis.
4. Genetic testing: To identify the type of gene mutation causing Leigh syndrome. This can include blood tests, cheek swabs, or urine samples.
5. Lactic acid measurement: Blood tests or cerebrospinal fluid (CSF) analysis to measure lactic acid levels.
6. Enzyme measurements: Blood tests to check for enzyme markers that indicate Leigh syndrome.

These diagnostic tests are used to confirm the clinical features of Leigh disease and establish a biochemical and genetic diagnosis.

Treatment Options for Leigh Disease

Leigh disease, also known as Leigh syndrome, is a rare and fatal genetic disorder that affects the nervous system. While there is no cure for the condition, various drug treatments have been explored to manage its symptoms and improve quality of life.

• Coenzyme Q10: This antioxidant has been shown to have therapeutic effects in treating Leigh disease [6][8]. Coenzyme Q10 helps to reduce oxidative stress and improve energy production in cells.
• L-carnitine: L-carnitine is an amino acid that plays a crucial role in the transport of fatty acids into mitochondria, where they are burned for energy. Supplementing with L-carnitine may help alleviate symptoms of Leigh disease [6].
• Alfa-lipoic acid: Alfa-lipoic acid is an antioxidant that has been shown to have neuroprotective effects and improve energy metabolism in cells. It may be beneficial in treating Leigh disease [6].
• Creatine monohydrate: Creatine is a naturally occurring substance that helps to supply energy to cells. Supplementing with creatine monohydrate may help alleviate symptoms of Leigh disease [6].
• Biotin, thiamine, and riboflavin: These B vitamins play important roles in energy metabolism and may be beneficial in treating Leigh disease [5][6].

Emerging Treatments

Recent research has also explored the use of other substances, including:

• Cannabidiol (CBD): CBD has been given orphan drug designation by the European Medicines Agency (EMA) to be used in the treatment of Leigh syndrome. While more research is needed, CBD may have therapeutic effects in reducing symptoms of the condition [9].

It's essential to note that these treatments are not curative and are aimed at managing symptoms and improving quality of life. A healthcare professional should be consulted for personalized advice on treating Leigh disease.

References:

[5] - There isn't a cure for Leigh syndrome. Treatments focus on easing symptoms to keep your child comfortable. Unfortunately, the condition is fatal. Your child may benefit from vitamins or cofactors like vitamin B1 (thiamine), vitamin B2 (riboflavin) and coenzyme Q10.

[6] - The drugs used for LS treatment include coenzyme Q10, L-carnitine, alfa-lipoic acid, creatine monohydrate, biotin, thiamine, and riboflavin. Decades of research have shown that these substances may help alleviate symptoms.

[8] - The drugs used for LS treatment include coenzyme Q10, L-carnitine, alfa-lipoic acid, creatine monohydrate, biotin, thiamine, and riboflavin. Decades of research have shown that these substances may help alleviate symptoms.

[9] - Cannabidiol has been given orphan drug designation by the European Medicines Agency (EMA) to be used in the treatment of Leigh syndrome, however more research is needed to confirm its effectiveness.

Leigh disease, also known as subacute necrotizing encephalopathy, is a rare genetic disorder that affects the nervous system. When considering differential diagnoses for Leigh disease, several conditions should be taken into account.

• Hypoxic-Ischemic Injury: This condition can cause similar symptoms to Leigh disease, including progressive neurological deterioration and loss of previously acquired motor skills [1].
• Glutaric Aciduria Type I: Also known as McLeod syndrome, this genetic disorder can lead to similar clinical presentations, such as developmental delays, seizures, and heart issues [2].
• Wilson's Disease: A genetic disorder that affects copper metabolism in the body, Wilson's disease can cause neurological symptoms like tremors, rigidity, and difficulty with coordination [3].
• Biotin-responsive basal ganglia disease: This rare condition is characterized by progressive neurological deterioration and can be mistaken for Leigh disease due to similar clinical presentations [4].
• Neuropathy, ataxia, and retinitis pigmentosa (NARP): A genetic disorder that affects the nervous system, NARP can cause symptoms like developmental delays, sensory polyneuropathy, and pigment retinopathy [5].

It's essential to note that these conditions should be considered in the differential diagnosis of Leigh disease. Accurate diagnosis requires a comprehensive evaluation by a healthcare professional.

References: [1] Context 8 [2] Context 7 [3] Context 8 [4] Context 9 [5] Context 7