Mitochondrial Disease Clinical Pathway — Emergency Department and Inpatient

Patients with Mitochondrial Disease

This pathway guides the ED care and inpatient care for patients of any age with:

Genetically confirmed, Primary (Definite) Mitochondrial Disease
Suspected Mitochondrial Disease

For individual patient information, refer to:

Metabolism/Mitochondrial Care Coordination notes
ED Patient Letter
Last Metabolism clinic note

Note: Patients may be followed at CHOP by Mitochondrial Medicine, Metabolism or Neurogenetics

Exclusions (see below)

Presence of other inborn errors of metabolism or primary genetic diseases that do not directly involve the mitochondria

Common Pediatric Mitochondrial Diseases: Acute and Chronic Symptoms

Disease	Symptoms of Acute Decompensation	Common (Chronic) Symptoms
Leigh Syndrome	Rapid progression to respiratory failure Dysphagia/drooling Profound (lactic) acidosis Cardiomyopathy Metabolic stroke: Increased weakness, seizures Hepatopathy Neuroregression	Global Developmental Delay Hypotonia/hypertonia Movement disorder Dysconjugate gaze Elevated lactate in blood and CSF Abnormal MRI brain Bilateral basal ganglia and/or brainstem lesions Eating & swallowing difficulties FTT Metabolic acidosis on bicarbonate supplementation
MELAS Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes	Stroke-like episodes: Focal neurological deficits Abnormal MRI brain with acute DWI+ Medically actionable with IV arginine Seizures: EPC (epilepsia partialis continua) or Status epilepticus	Migraine Vision loss Hemiplegia Seizures Short stature, FTT Deafness Diabetes Hyperglycemia, hypoglycemia Avoid over treating DM results from insulin deficiency and resistance Elevated lactate w/wo metabolic acidosis
POLG Polymerase gamma 1 Most common form in children: Alpers-Huttenlocher Syndrome	Seizures: Refractory status epilepticus Epilepsia partialis continua (EPC) Continuous focal seizure or myoclonus Fulminant liver failure: Avoid Valproic acid/Depakote and derivatives Provoked by fever, infection	Developmental regression Fluctuating LFTs Elevated CSF protein Cerebral folate deficiency Brain MRI may show global atrophy or stroke like lesions
PDH Pyruvate dehydrogenase deficiency	Seizures (infantile spasms) May be on KETOGENIC Diet	Lactic acidosis, high pyruvate Metabolic acidosis (may need sodium bicarb) Ataxia Growth delay, FTT Hypotonia Polyneuropathy Brain MRI: agenesis of the corpus callosum, cerebral cysts, Leigh syndrome
Kearns-Sayre Syndrome (KSS) due a single large scale mtDNA deletion	Hypocalcemia/hypoparathyroidism: Tetany, seizures, rickets Diabetes mellitus Pancreatitis/pancreatic insufficiency Stroke-like episodes	CPEO (chronic progressive external ophthalmoplegia) SNHL (sensorineural hearing loss) Elevated CSF protein Cerebral folate deficiency Ataxia FTT, short stature Renal failure Hepatopathy Brain MRI Leigh syndrome or white matter changes Cardiac conduction defects (some have pacemaker)

Exclusions

Disease Description	EXAMPLES
Inborn errors of metabolism: Metabolic diseases that involve non-respiratory chain mitochondrial proteins	Fatty acid oxidation defects Mitochondrial trifunctional protein (TFP, CPT2, CACT, LCHAD) Urea cycle defects (i.e. Ornithine Transcarbamylase Deficiency) Organic acidopathies e.g. MMA, PA, IVA, GA-1, cobalaminopathy Aminoacidopathies e.g. MSUD, PKU
Primary Genetic Disease that does not directly involve the mitochondria, but has been reported to have “secondary mitochondrial dysfunction”	Trisomy 21 22q11.2 microdeletion syndrome Cornelia de Lange syndrome Rett syndrome Cockayne syndrome Angelman syndrome STXBP1-related epilepsy NBIA disorders (i.e. PKAN, BPAN)

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The clinical pathways are based upon publicly available medical evidence and/or a consensus of medical practitioners at The Children’s Hospital of Philadelphia (“CHOP”) and are current at the time of publication. These clinical pathways are intended to be a guide for practitioners and may need to be adapted for each specific patient based on the practitioner’s professional judgment, consideration of any unique circumstances, the needs of each patient and their family, and/or the availability of various resources at the health care institution where the patient is located.

Accordingly, these clinical pathways are not intended to constitute medical advice or treatment, or to create a doctor-patient relationship between/among The Children’s Hospital of Philadelphia (“CHOP”), its physicians and the individual patients in question. CHOP does not represent or warrant that the clinical pathways are in every respect accurate or complete, or that one or more of them apply to a particular patient or medical condition. CHOP is not responsible for any errors or omissions in the clinical pathways, or for any outcomes a patient might experience where a clinician consulted one or more such pathways in connection with providing care for that patient.