Leigh syndrome spectrum

Leigh syndrome spectrum (LSS) is a group of mitochondrial energy disorders with overlapping neurologic and systemic features. It can result from pathogenic variants in mitochondrial DNA or in many different nuclear genes. Onset is often in infancy or childhood but can occur from the prenatal period through adulthood. Course, organs affected, inheritance, and treatment implications depend heavily on the molecular cause.1

Urgent safety

People with LSS should have an individualized emergency plan from their metabolic or mitochondrial team. Seek emergency care for new breathing difficulty, blue or gray color, reduced consciousness, a prolonged or repeated seizure meeting the plan's threshold, sudden weakness or loss of skills, or inability to maintain hydration.13

Illness, persistent vomiting, surgery, anesthesia, or prolonged fasting can precipitate metabolic decompensation. Contact the specialist team early when intake falls or illness develops and bring the emergency plan to urgent care. Do not improvise fasting, fluid, glucose, supplement, or rescue protocols from a general webpage because gene-specific exceptions matter.3

Clinical pattern and diagnosis

Possible features include:

• developmental delay, episodic or sustained regression, weakness, hypotonia, spasticity, dystonia, or ataxia;
• brainstem involvement affecting breathing, swallowing, eye movement, hearing, or alertness;
• seizures, movement disorders, optic atrophy, nystagmus, or peripheral neuropathy;
• poor growth, feeding difficulty, recurrent vomiting, and exercise intolerance;
• cardiac, liver, kidney, endocrine, blood, or other systemic involvement in some molecular forms.

Diagnosis combines the clinical course with brain MRI, laboratory evaluation, and molecular testing. Characteristic bilateral basal-ganglia or brainstem lesions support LSS, but imaging varies. Elevated blood or cerebrospinal-fluid lactate can support a mitochondrial diagnosis; normal lactate does not exclude LSS. Broad nuclear and mitochondrial DNA testing may be needed, and tissue testing is sometimes considered by specialists.1

“Leigh-like syndrome” is older terminology now included within Leigh syndrome spectrum. A molecular diagnosis is important because inheritance may be autosomal recessive, mitochondrial, X-linked, or rarely autosomal dominant, and recurrence counseling differs accordingly.1

Treatment and planning

There is no single treatment for LSS. Some molecular causes have targeted vitamin, cofactor, dietary, or other treatments, while the same approach may be ineffective or inappropriate for another cause. Do not start a “mitochondrial cocktail,” restrictive diet, or medication change without metabolic or mitochondrial specialist review.13

Care may include neurology, metabolic medicine, respiratory and sleep care, cardiology, gastroenterology and nutrition, hearing and vision, rehabilitation, palliative care, and other specialties according to findings and goals. Procedures and anesthesia need advance planning with the mitochondrial team. Mobility, exercise, seating, and feeding plans should adapt to current endurance and the possibility of fluctuation or regression.

Swallowing and communication

Urgent swallowing review is needed for new choking, wet or changed voice, inability to clear secretions, recurrent respiratory symptoms, dehydration, or rapid decline in eating. Texture, posture, pacing, equipment, and tube-feeding decisions require direct assessment coordinated with respiratory, nutrition, and metabolic care.1

Communication may change with fatigue, illness, seizures, motor impairment, vision or hearing loss, respiratory support, or regression. Preserve the person's established language and decision-making role. Use extra response time, reduce effort and competing demands, and confirm the intended message.

AAC may be temporary, part-time, or long-term. Options include writing, alphabet or topic boards, stored messages, text-to-speech, partner-assisted scanning, switches, and speech-generating systems. Trial access from current vision, hearing, movement, posture, alertness, and endurance rather than the diagnosis. Keep urgent messages and an agreed yes/no response available, train partners, and maintain a low-tech backup.4 For evaluation, trials, funding, and implementation, use the AAC device acquisition guide.

Coding

• ICD-10-CM G31.82: Leigh's disease.

The descriptor does not identify the molecular cause, inheritance, manifestations, or current metabolic state. Code associated conditions only when documented and supported by current local rules.5

Sources

1. Rahman, Thorburn, and Ball. Nuclear Gene-Encoded Leigh Syndrome Spectrum Overview, GeneReviews — current terminology, diagnosis, molecular diversity, management, and inheritance (updated 2025).
2. Rahman, Thorburn, and Ball. Mitochondrial DNA-Associated Leigh Syndrome Spectrum, GeneReviews — mitochondrial-DNA causes, diagnosis, management, and maternal inheritance.
3. Parikh et al. Patient care standards for primary mitochondrial disease — Mitochondrial Medicine Society consensus on illness, emergency, medication, fasting, procedures, and multisystem care (PMID 28749475).
4. American Speech-Language-Hearing Association: Augmentative and Alternative Communication — individualized, multimodal AAC assessment.
5. Centers for Medicare & Medicaid Services: FY2026 ICD-10-CM definitions — G31.82 descriptor.

Review boundary

This page cannot diagnose LSS, interpret genetic or metabolic results, or supply an emergency, fasting, anesthesia, medication, supplement, or nutrition protocol. Emergencies require immediate local assessment. All treatment, diet, procedure, mobility, feeding, and communication decisions require direct review with the specialist team and the person or family.