Clinical Guidance

MPV17-related mtDNA maintenance defect has been reported in 100 individuals [, , , , , , , , , , , , , , , , , , , , , , , , , ]. The vast majority of affected individuals (96/100) presented with an early-onset encephalohepatopathic (hepatocerebral) disease affecting mainly the nervous system and liver; mtDNA depletion is typically identified, particularly in liver. A later-onset neuromyopathic disease characterized by myopathy and neuropathy and associated with multiple mtDNA deletions in muscles has also rarely been described (4/100 affected individuals) . MPV17-related mtDNA maintenance defect, encephalohepatopathy form is typically an early-onset disease that presents during the neonatal period (36 out of 96; 38%) or infancy (56 out of 96; 58%). Childhood onset (2-18 years) has been reported on rare occasions (4 out of 96; 4%) . Clinical manifestations include hepatic and neurologic findings summarized in . Table 2. Clinical Manifestations of MPV17-Related Encephalohepatopathy Clinical Manifestations | Frequency Hepatic

Diagnostic Criteria

Suggestive Findings

MPV17-related mitochondrial DNA (mtDNA) maintenance defect should be suspected in individuals with the following clinical features, brain MRI findings, and supportive laboratory findings.

Clinical features

• Hepatic

• Liver dysfunction or failure

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with MPV17-related mtDNA maintenance defect, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 5. Recommended Evaluations Following Initial Diagnosis in Individuals with MPV17-Related mtDNA Maintenance Defect

Surveillance Guidelines

No clinical guidelines for surveillance are available. The following evaluations are suggested, with frequency varying according to the severity of the condition:

Table 7.

Recommended Surveillance for Individuals with MPV17-Related mtDNA Maintenance Defect

System/Concern | Evaluation | Frequency

Gastrointestinal