Mitochondrial Disorders | The Massachusetts General Hospital Handbook of Neurology

Authors: Flaherty, Alice W.; Rost, Natalia S.

Title: Massachusetts General Hospital Handbook of Neurology, The, 2nd Edition

> Table of Contents > Adult Neurology > Mitochondrial Disorders

Mitochondrial Disorders

A. H&P

Stroke-like episodes, migraines, developmental delay, encephalopathy, failure to thrive, hypotonia, ataxia, weakness, exercise intolerance, lethargy, muscle cramps, hearing loss, blindness, glucose intolerance, seizures, constipation, GERD. Family history.

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B. Tests

1. For crisis: Infectious workup, brain MRI/MR spectroscopy, EEG, serum lactate, pyruvate, lytes, LFTs, NH₃, ABG (pH), U/A. CSF lactate, pyruvate, EKG.
2. Diagnostic workup: Above plus serum ketones, lactate and pyruvate (more sensitive after a crisis), quantitative amino acids, 3-methylglucaconic acid, carnitine, urine organic acids, very long chain fatty acids, WBC lysosomal enzymes. EMG, EKG, echocardiogram. Muscle biopsy (try weakest muscle), mitchondrial DNA analysis. CSF alanine, glycine.

C. Cause

Inherited or spontaneous mutations in mtDNA or nuclear DNA. Genocopies (extreme clinical heterogeneity with identical mutations) and phenocopies (different mutations with same disease) are the rule. MtDNA varies within cells and between cells (heteroplasmy).

Table 17. Symptoms of mitochondrial disorders. See text for abbreviations.

	CPEO	MERRF	MELAS
Weakness		+	+
Ragged red fibers	+	+	+
Short stature	+	+	+
Deafness	+	+	+
Dementia	+	+	+
Spongy brain degen.	+	+	+
Ophthalmoplegia	+
Retinal degeneration	+
Heart block	+
CSF protein >100 mg/dL	+
Myoclonus
Ataxia		+
Seizures		+	+
Vomiting			+
Cortical blindness			+
Hemiparesis			+

D. Congenital progressive external ophthalmoplegia (CPEO)

AKA Kearns-Sayre syndrome. See Table 17; also see bilateral ptosis, mild proximal myopathy.

E. Leber's hereditary optic neuropathy

Progressive blindness from optic atrophy.

F. Leigh's dz

(Subacute necrotizing encephalomyelopathy): Usually pediatric, with hypotonia, developmental delay, apneic episodes; sometimes seizures, ataxia, neuropathy, ophthalmoplegia.

G. MERRF

(myoclonic epilepsy with ragged red fibers): See Table 17.

H. MELAS

(mitochondrial encephalopathy with lactic acidosis and stroke-like episodes): See Table 17.

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I. Neuropathy, ataxia, and retinitis pigmentosa

Also see growth retardation, dementia.

J. Treatment

1. General: Avoid extreme temps, toxins (ETOH, cigarettes, ASA), meds that compromise mitochondria (DPH, phenobarbital, valproate, tetracycline). Coenzyme Q₁₀ 4 mg/kg/d, B50 complex (B₁, B₂, etc.), vitamin E 100-400 IU/d, L-carnitine 100 mg/kg/d.
2. Crisis: Hydrate, treat infection and seizures. Add vitamin C 1,000 mg/d, zinc 30 mg/d, biotin 10 mg/d, -lipoic acid 10 mg/kg/d.