Mitochondrial DNA-associated Leigh syndrome

What it is

From: Orphanet

Maternally inherited Leigh syndrome is a rare subtype of Leigh syndrome characterized clinically by encephalopathy, lactic acidosis, seizures, cardiomyopathy, respiratory disorders and developmental delay, with onset in infancy or early childhood, and resulting from maternally-inherited mutations in mitochondrial DNA.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormality of Krebs cycle metabolism · Very frequent (99-80%)

An abnormality of the tricarboxylic acid cycle.

Increased CSF lactate · Very frequent (99-80%)

Increased concentration of lactate in the cerebrospinal fluid.

Ataxia · Frequent (79-30%)

Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).

Bilateral tonic-clonic seizure · Frequent (79-30%)

A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.

Chorea · Frequent (79-30%)

Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities.

Dyskinesia · Frequent (79-30%)

A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.

Dystonia · Frequent (79-30%)

An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.

Episodic vomiting · Frequent (79-30%)

Paroxysmal, recurrent episodes of vomiting.

Failure to thrive · Frequent (79-30%)

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Floppy infant · Frequent (79-30%)

Floppiness/hypotonia is defined as reduced resistance to passive movement of joints. Physical examination of floppy/hypotonic infants shows head lag, lack of shoulder and elbow muscle contraction on traction response, inability to tighten the shoulder girdle muscles (or slipping through) when held under the axillae, scarf sign (when the arm is pulled to the opposite side, the arm wraps around the neck with the elbow crossing midline), hyperdorsiflexion of the feet, easy apposition of the thumb against the forearm, feet touching the cheek with ease and without discomfort, frog leg position, and inverted U sign on ventral suspension (head, arms, and legs hanging down without elbow or knee flexion and the trunk rounded in a dome shape).

Focal T2 hyperintense basal ganglia lesion · Frequent (79-30%)

A lighter than expected T2 signal on magnetic resonance imaging (MRI) of the basal ganglia. This term refers to a localized hyperintensity affecting a particular region of the basal ganglia.

Gait ataxia · Frequent (79-30%)

A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.

Generalized myoclonic seizure · Frequent (79-30%)

A generalized myoclonic seizure is a type of generalized motor seizure characterized by bilateral, sudden, brief (<100 ms) involuntary single or multiple contraction of muscles or muscle groups of variable topography (axial, proximal limb, distal). Myoclonus is less regularly repetitive and less sustained than is clonus.

Hypertonia · Frequent (79-30%)

A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.

Other findings in the same source

From: Orphanet

Additional reported features include Increased circulating lactate concentration (Frequent (79-30%)); Lacticaciduria (Frequent (79-30%)); Muscle weakness (Frequent (79-30%)); Ophthalmoparesis (Frequent (79-30%)); Pigmentary retinopathy (Frequent (79-30%)); Seizure (Frequent (79-30%)); Severe global developmental delay (Frequent (79-30%)); Spasticity (Frequent (79-30%)); Sensorimotor neuropathy (Frequent (79-30%)); Abnormal renal tubule morphology (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Childhood; Infancy

Inheritance in the source

From: Orphanet

Mitochondrial inheritance

Frequency and the population described

From: Orphanet

Prevalence at birth: Unknown; Worldwide; Class only. Point prevalence: Unknown; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

Mitochondrial inheritance refers to changes in mitochondrial DNA, which is passed through egg cells. The pattern and expression of mitochondrial disease can be complex. Conditions involving mitochondrial function may also involve nuclear genes, so a specialist needs the exact molecular diagnosis before explaining family implications.

Which doctor should you see?

The suggested department for discussing Mitochondrial DNA-associated Leigh syndrome is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Mitochondrial DNA-associated Leigh syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.