Table 6. [Mitochondrial DNA-Associated Leigh Syndrome Spectrum: Treatment of Manifestations]. - GeneReviews®

Manifestation/Concern	Treatment	Considerations/Other
Acute acidosis	Sodium bicarbonate or sodium citrate for significant acidosis Consider THAM if accompanying hypernatremia.	Avoid lactate containing solutions (e.g., Ringer lactate).
Epilepsy	Treatment w/ASM byexperienced neurologist	Sodium valproate should be avoided because of its inhibitory effects on mitochondrial respiratory chain. ¹ Education of parents/caregivers ²
Dystonia	Benzhexol, baclofen, tetrabenazine, & gabapentin may be useful, alone or in various combinations.	An initial low dose should be started & gradually ↑ until symptom control is achieved, or intolerable side effects occur.
Botulinum toxin injection has been used in persons w/LSS & severe intractable dystonia.	Use w/caution given potential side effects of exacerbating muscle weakness; & do not use in head & neck because of risk of adverse events (e.g., impaired swallow).
Pulmonology	Referral to pulmonologist as needed Ventilatory support for persons w/respiratory compromise
Feeding/Nutrition	Caloric & nutritional supplementation as needed (incl micronutrients) Feeding therapy as needed Gastrostomy tube placement may improve nutritional intake for those w/persistent feeding issues, choking, or aspiration risk due to dysphagia.	Low threshold for clinical feeding eval &/or radiographic swallowing study when showing clinical signs or symptoms of dysphagia
Development/Cognition	See Developmental Delay / Intellectual Disability Management Issues.
Myopathy &/or ataxia	PT & OT	Equipment to prevent falling & maintain independent mobility as appropriate
Eyes	Standard treatments for eye movement disorders as advised by ophthalmologist
Cardiomyopathy	Anticongestive therapy or antiarrhythmic therapy may be required & treatment should be managed by cardiologist.
Gastrointestinal	Stool softeners, laxatives for constipation as needed
Liver	Treatments for liver failure as advised by hepatologist
Renal	Electrolyte monitoring & replacement for renal tubular losses per nephrologist
Hearing	Hearing aids or cochlear implants for sensorineural hearing loss Referral to speech therapy Referral to hearing support services	Counsel to avoid excessive noise exposure, which can exacerbate hearing loss.
Endocrine	Treatment for diabetes mellitus or adrenal insufficiency managed by endocrinologist
Psychosocial	Standard treatments of anxiety &/or depression
Family/Community	Ensure appropriate social work involvement to connect families w/local resources, respite, & support. Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.	Ongoing assessment of need for palliative care involvement &/or home nursing

Manifestation/Concern

Treatment

Considerations/Other

Acute acidosis

Sodium bicarbonate or sodium citrate for significant acidosis
Consider THAM if accompanying hypernatremia.

Avoid lactate containing solutions (e.g., Ringer lactate).

Epilepsy

Treatment w/ASM byexperienced neurologist

Sodium valproate should be avoided because of its inhibitory effects on mitochondrial respiratory chain. ¹
Education of parents/caregivers ²

Dystonia

Benzhexol, baclofen, tetrabenazine, & gabapentin may be useful, alone or in various combinations.

An initial low dose should be started & gradually ↑ until symptom control is achieved, or intolerable side effects occur.

Botulinum toxin injection has been used in persons w/LSS & severe intractable dystonia.

Use w/caution given potential side effects of exacerbating muscle weakness; & do not use in head & neck because of risk of adverse events (e.g., impaired swallow).

Pulmonology

Referral to pulmonologist as needed
Ventilatory support for persons w/respiratory compromise

Feeding/Nutrition

Caloric & nutritional supplementation as needed (incl micronutrients)
Feeding therapy as needed
Gastrostomy tube placement may improve nutritional intake for those w/persistent feeding issues, choking, or aspiration risk due to dysphagia.

Low threshold for clinical feeding eval &/or radiographic swallowing study when showing clinical signs or symptoms of dysphagia

Development/Cognition

See Developmental Delay / Intellectual Disability Management Issues.

Myopathy &/or ataxia

PT & OT

Equipment to prevent falling & maintain independent mobility as appropriate

Eyes

Standard treatments for eye movement disorders as advised by ophthalmologist

Cardiomyopathy

Anticongestive therapy or antiarrhythmic therapy may be required & treatment should be managed by cardiologist.

Gastrointestinal

Stool softeners, laxatives for constipation as needed

Liver

Treatments for liver failure as advised by hepatologist

Renal

Electrolyte monitoring & replacement for renal tubular losses per nephrologist

Hearing

Hearing aids or cochlear implants for sensorineural hearing loss
Referral to speech therapy
Referral to hearing support services

Counsel to avoid excessive noise exposure, which can exacerbate hearing loss.

Endocrine

Treatment for diabetes mellitus or adrenal insufficiency managed by endocrinologist

Psychosocial

Standard treatments of anxiety &/or depression

Family/Community

Ensure appropriate social work involvement to connect families w/local resources, respite, & support.
Coordinate care to manage multiple subspecialty appointments, equipment, medications, & supplies.

Ongoing assessment of need for palliative care involvement &/or home nursing

From: Mitochondrial DNA-Associated Leigh Syndrome Spectrum

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

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