Oxford Patient Information Event 2017

Mitochondrial Disease in Children: Practical Advice & Current Drug Studies

Dr Victoria NesbittSenior Paediatric Registrar

John Radcliffe Hospital, Oxford

Overview

• Mitochondrial disease in children

• Practical advice

• Current studies–EPI‐743–MitoCohort UK

Phenotypic spectrum of mitochondrial disease

Adapted from Khan et al. Mitochondrial disorders: Challenges in diagnosis & treatment 2015

Eyes: ophthalmoplegia, ptosis, retinitis pigmentosa, optic atrophy, cataracts

Thyroid: hypothyroidism, hypoparathyroidism

GI system: dysphagia, vomiting, constipation, chronic diarrhoea, pseudo‐obstruction

Pancreas: diabetes

Reproductive system (female): delayed puberty, infertility, miscarriage

Skeletal muscle: fatigue, myopathy, exercise intolerance, myalgia, cramps, myoglobinuria

Growth: short stature

Nervous system: developmental delay / regression, abnormal tone, ataxia, deafness, dementia, depression, encephalopathy, migraine, myoclonus, peripheral neuropathy, seizures, stroke

Heart: cardiomyopathy, conduction block, Wolff‐Parkinson White syndrome, sudden death

Liver: failure, hepatic stenosis

Kidneys:  Fanconi syndrome, nephroticsyndrome

Reproductive system (male): delayed puberty, infertility

Used with kind permission

Mitochondrial disease in childhood

Mitochondrial Syndromes in Children

Mitochondrial disease

Leigh’sAlper’s

MDDS 

MNGIE

GRACILE

MEGDELSenger’s

NARP

CPEO

Pearson’s

KSS

MELAS

mtDNA disease in childhood

0 5 10 15 20 25 30

Developmental delayConstipation

Hearing impairedFatigue

DysphagiaSeizuresAtaxia

Abnormal toneProximal myopathy

RetinopathySOBOE

Low moodMigraine

PtosisCardiac arrhythmia

Supplementary feedsEncephalopathyOpthalmoplegiaCardiomyopathy

LVHMyalgia

Reduced exercise toleranceBradykinesia

SLEsScoliosis

Peripheral neuropathyAspiration pneumonia

Delayed pubertyDiabetesAnorexia

HyperactivityNystagmus

Movement disorderHyponatraemia

CRFPseudo‐obstruction

Any organAny ageAny time

Practical Advice Overview

Education

Holidays

Operations Meds toavoid

Illnesses

Diet & nutrition

Exercise

Imms & vaccines

Exercise• Exercise:

– Improves energy production

– Helps maintain muscle strength

– Improves mood

– Decreases risk of heart disease & diabetes

– Promotes independence

• Research suggests:– Better use of oxygen

– More efficient metabolism

– Increased numbers of healthy mitochondria

– Increased enzyme complex levels

– Lower mutation load & increased functional mitochondrial load

– Improved quality of life

Exercise

• What is the best exercise?– Can be done easily– Low impact– Does not cause excess fatigue– Still allows ‘routine’ activity

Diet & Nutrition• Balanced diet

– Slow release carbohydrates– Balanced with protein, vegetables/fruit

• Good hydration

• Avoid fasting and dehydration

• Small, little, often!

• Multi‐vitamin

• Ubiquinone trial if fatigued

• Riboflavin +/‐ thiamine for specific patients

Medications to avoid• Sodium valproate

• Metformin

• Linezolid

• Zidovudine

• Gentamicin (m.1555A>G)

• Statins (blood monitoring)

• Check interactions with regular medications

Immunisations & vaccinations

• Continue with routine immunisations• Annual ‘flu’ and pneumococcal vaccine

• Holiday vaccines:– Discuss with your mitochondrial team– Given well in advance– Caution with anti‐malarials and anti‐epileptics

Intercurrent illnesses

• Personal information sheet• Direct access to local DGH

• Ensure hydration– Dioralyte / electrolade

• Eat little and often if possible• Regular paracetamol* if febrile• Continue regular medication

– diabetics to contact local team for advice

* unless contraindicated

Operations• Inform your mitochondrial team!

• May need additional pre‐op investigations

• Anaesthetist to be aware

• Minimise fasting period

• Continue regular medications

• May need PICU / PHDU bed post‐op

Education• Important socially!

• Regular fluids, snacks pre‐exercise,awareness of condition / needs / illness

• Statement of Special Educational Needs

• Education Health Care Plan– Children & young people <25yrs who need more support than that available through SEN

– Identifies educational, health and social needs and sets out additional support to meet those needs

Coping with mitochondrial diseaseStress related to ambiguityStress related to ambiguity

Uncertain geneticsUncertain genetics

PrognosisPrognosis

Coping with uncertaintyCoping with uncertainty

GriefGrief

Lack of awarenessLack of 

awareness

Re‐thinking expetctationsRe‐thinking expetctations

Educating others

Educating others

Practical Advice Summary

Education

Holidays

Operations Meds toavoid

Illnesses

Diet & nutrition

Exercise

Imms & vaccines

EPI‐743

• Vincerinone (Edison Pharmaceuticals)– Type of CoEnzyme Q10

• Anti‐oxidant• More potent & more highly absorbed

– ? Increase the amount of energy mitochondria can produce & therefore ? reduce symptoms of mitochondrial disease

– US trial (2012) 10 patients exhibited reversal or slowing of disease progression and no obvious adverse effects to the drug• ? placebo effect

– Extended trial (invitation only) ending April 2017– Currently no UK licence

MRC Mitochondrial Disease Patient Cohort Study (UK)

Questions?