A recent review provides advice for the evaluation of the child with suspected mitochondrial liver disease (JPGN 2013; 57: 269-79).
- Acute in a child with no history of hepatic dysfunction
- Chronic liver and CNS dysfunction
- Onset of liver disease in patient with known CNS disorder
Suggested Tiered Diagnostic Evaluation: Table 1 provides extensive suggestions.
- 1st tier: CMP, INR, AFP, CPK, Phos, CBC/d, ammonia, Lactate/pyruvate (preferably 1 hour after feeding), serum ketone bodies, serum acylcarnitine profile, carnitine profile, urine organic acids, serum amino acids, urine acylglycines and 2-ethylmalonic acid quantification, plasma thymidine (especially if intestinal dysmotility), quantitative serum methylmalonic acid, CSF analysis (lactate and pyruvate, amino acids, protein)
- 2nd tier: genotyping for more common genes (eg. panel with POLG1, DGUOK, MPV17), other genetic tests based on tier 1 testing (see table for details)
- 3rd tier: liver biopsy, skin biopsy, and muscle biopsy (see table for details)
- 4th tier: additional genetic tests based on 1st three tiers
Table 2 describes potential evaluations in other organs. For example, for brain, MRI, EEG and CSF.
Table 3 lists ~27 mutation/syndromes and clinical features.
The last three words from the conclusion of the publication are not supported by the review. The authors state that this systematic approach “can aid in making a timely, accurate, and cost-effective diagnosis.” While the authors do not provide estimates of the expense of these tests, they are probably very expensive, though less costly than a failed liver transplantation.
Bottomline: “Available technology to aid in diagnosis has improved substantially. Nonetheless, diagnosis of suspected mitochondrial disease in children is complicated.”
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