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.
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. | |||||||||||
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