Leigh syndrome: symptoms, causes, diagnosis and care in the UK

Leigh syndrome is named after the British neuropsychiatrist Archibald Denis Leigh, who first described it in 1951, according to the Lily Foundation. It is also called Leigh’s disease, subacute necrotising encephalomyelopathy or mitochondrial Leigh disease. The charity describes it as the most common form of mitochondrial disease in childhood.

Mitochondria are the structures within cells that make energy. When they fail, tissues with high energy demands, particularly the brain and muscles, are affected first. In Leigh syndrome, the Lily Foundation says, mutations in mitochondrial DNA or nuclear DNA impair the body’s ability to produce energy, and the condition is progressive, with symptoms worsening over time.

Contact, a UK charity for families with disabled children, describes it as a disease that affects the brain and gets worse over time, with changes in the cell’s pathway for producing energy as the underlying cause.

Symptoms vary with the age of onset and the specific gene involved. The Lily Foundation says one of the key features is loss of previously acquired motor or intellectual skills, often triggered by a minor illness such as a cold, cough or tummy bug. Contact says the first problems in young children are often poor weight gain and floppiness, and that later problems commonly include stiffness or tremor, abnormal eye movements and difficulty swallowing.

• Delayed development, or loss of skills already gained (regression).

• Poor muscle tone (hypotonia).

• Movement disorders such as dystonia, or difficulty with co-ordination (ataxia).

• Trouble breathing or swallowing, and feeding difficulties.

• Seizures.

• Lactic acidosis, meaning excess lactic acid in the body.

• Vision and hearing loss.

Contact explains that most patients start having problems by the age of two years, and that there is typically a stepwise downhill course: patients may deteriorate rapidly and then partly recover over a few weeks, followed by periods of stability. It also says that others have their first problems later in childhood and often survive into adulthood.

The Lily Foundation says that, as one of the most severe forms of mitochondrial disease, Leigh syndrome generally results in a limited life expectancy and usually needs specialised care and support. It quotes research using global patient data in which children were usually diagnosed at an average age of 2.8 years, with time to diagnosis often taking 6 months to a year, and in which the average life expectancy was around 3.5 years. Those figures describe a group of patients in studies, and individual courses differ widely, so they should be discussed with the child’s own specialist team.

The same page notes that as the disease progresses, neurological functions become more severely impaired, with outcomes in one Newcastle report including wheelchair use, tube feeding and one-to-one support. The adult-onset form is described as very rare, with neurological problems that progress slowly.

The Lily Foundation says Leigh syndrome can be caused by mutations in more than 75 different genes affecting mitochondrial function, either nuclear genes or mitochondrial genes. In confirmed cases it reports that nuclear DNA mutations were the most common cause in one study and that mitochondrial DNA mutations were also common, with the most frequent individual genes including SURF1, ECHS1, NDUFV1 and MT-ATP6.

Inheritance therefore differs between families. Contact says the patterns include autosomal recessive inheritance and “maternal inheritance”, which is due to mutations in mitochondrial DNA, and that other cases are caused by new mutations with a very low recurrence risk. Prenatal diagnosis is available in some cases of Leigh syndrome but not all.

The Lily Foundation estimates incidence at approximately 1 in 77,000 births, or 1 in 40,000 when including Leigh-like disease, and adds that this may be an underestimate because mitochondrial diseases are frequently under-diagnosed or misdiagnosed.

Contact says diagnosis of Leigh syndrome is difficult. Scans usually show changes in parts of the brain called the brainstem and basal ganglia, and there tends to be a high level of lactic acid in the cerebrospinal fluid. Tests on muscle and skin biopsies can usually identify the underlying biochemical abnormality and lead to molecular tests.

The Lily Foundation describes the same process in more general terms: identifying typical symptoms such as developmental regression, muscle weakness and poor weight gain, together with laboratory tests for high lactic acid, blood tests and often an MRI. Sometimes a muscle or skin biopsy is done, while panel testing or genetic sequencing is used to confirm the diagnosis and identify the exact gene.

Identifying the gene matters because it informs inheritance and family planning. The Lily Foundation notes that genetic counselling is available through NHS services to help families understand inheritance patterns.

Contact says that in the vast majority of patients there is no effective treatment, and that supportive measures are important and may include physiotherapy, muscle relaxants and tube feeding through a gastrostomy. The Lily Foundation similarly says that specialised care and support are usually needed.

The Lily Foundation says specialist mitochondrial clinics across the UK provide expert care, including diagnosis, ongoing monitoring and symptom management. It reports that its content was reviewed by Professor Robert McFarland, Director of the NHS Highly Specialised Service for Rare Mitochondrial Disorders. Contact points families to Metabolic Support UK for information and support.

Because illness can trigger setbacks, families often find it helpful to agree a plan with the metabolic team for what to do during infections. The sources used for this page do not give specific illness-management protocols, so those should come from the child’s own clinicians.

Diagnosis and care for Leigh syndrome in the UK are provided through NHS paediatric neurology and metabolic services, with highly specialised mitochondrial services for rarer conditions. Families are usually referred by a paediatrician or GP and followed up by a multidisciplinary team.

Some families seek an additional opinion privately or abroad, particularly for research opportunities. It is sensible to share any outside advice with the NHS team so that care remains co-ordinated.