Diagnostic Criteria

No consensus clinical diagnostic criteria for SUCLA2-related mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (SUCLA2-related mtDNA depletion syndrome) have been published.

Suggestive Findings

SUCLA2-related mtDNA depletion syndrome typically manifests during early infancy and should be suspected in a proband with a combination of the following clinical, brain MRI, and supportive laboratory findings and family history.

Clinical findings

• Developmental delay (DD)/ intellectual disability (ID). Mild-to-profound developmental delay and intellectual disability

• Neuromuscular features

• Hypotonia, axial or generalized

• Dystonia

• Muscle atrophy

• Sensorineural hearing impairment

• Feeding and growth issues

Source: GeneReviews — "SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria"

Differential Diagnosis

SUCLA2-related mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (SUCLA2-related mtDNA depletion syndrome) needs to be differentiated from other mtDNA depletion syndromes, a genetically and clinically heterogeneous group of primarily autosomal recessive disorders that are characterized by a severe reduction in mtDNA content leading to impaired energy production in affected tissues and organs . Mitochondrial DNA depletion syndromes occur as a result of defects in mtDNA maintenance caused by pathogenic variants in nuclear genes that function in either mitochondrial nucleotide synthesis (TK2, SUCLA2, SUCLG1, RRM2B, DGUOK, and TYMP) or mtDNA replication (POLG, TWNK, TFAM, RNASEH1, MGME1) and are phenotypically classified into hepatocerebral, encephalomyopathic, encephaloneuropathic, neurogastrointestinal, and myopathic forms . See also the Mitochondrial DNA Maintenance Defects Overview. The phenotype of SUCLG1-related mtDNA depletion syndrome may be difficult to distinguish from SUCLA2-related mtDNA depletion syndrome. SUCLG1-related mtDNA depletion syndrome is characterized by developmental delay, intellectual disability, hypotonia, muscle atrophy, feeding difficulties, growth restriction, dystonia, hearing loss, lactic acidosis, elevated urine and plasma methylmalonic acid, and mtDNA depletion. However, hepatopathy and cardiomyopathy occur in SUCLG1-related mtDNA depletion only. Table 3. Mitochondrial DNA Depletion Syndromes

Management Guidelines

No clinical practice guidelines for SUCLA2-related mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (SUCLA2-related mtDNA depletion syndrome) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with SUCLA2-related mtDNA depletion syndrome, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria: Recommended Evaluations Following Initial Diagnosis

Source: GeneReviews — "SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 6. SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria: Recommended Surveillance

Source: GeneReviews — "SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic Form with Methylmalonic Aciduria"