Clinical characteristics: SUCLG1-related mitochondrial DNA (mtDNA) depletion syndrome, encephalomyopathic form with methylmalonic aciduria is characterized in the majority of affected newborns by hypotonia, muscle atrophy, feeding difficulties, and lactic acidosis. Affected infants commonly manifest developmental delay / cognitive impairment, growth retardation / failure to thrive, hepatopathy, sensorineural hearing impairment, dystonia, and hypertonia. Notable findings in some affected individuals include hypertrophic cardiomyopathy, epilepsy, myoclonus, microcephaly, sleep disturbance, rhabdomyolysis, contractures, hypothermia, and/or hypoglycemia. Life span is shortened, with median survival of 20 months.
Diagnosis/testing: The diagnosis of SUCLG1-related mtDNA depletion syndrome is established in a proband by the identification of biallelic pathogenic variants in SUCLG1 on molecular genetic testing.
Management: Treatment of manifestations: Management is supportive and is best provided by a multidisciplinary team. Treatment may include physical therapy to help maintain muscle function and prevent joint contractures, nutritional support by a dietitian, use of a nasogastric tube or gastrostomy tube feedings, chest physiotherapy, and aggressive antibiotic treatment of chest infections. When present, seizures are treated using standard anti-seizure medication.
Surveillance: The suggested evaluations (with frequency varying according to the needs of the child) can include developmental and neurologic assessment, nutritional and growth assessment, echocardiogram, liver function tests, hearing evaluation, and ophthalmologic examination.
Genetic counseling: SUCLG1-related mtDNA depletion syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the SUCLG1 pathogenic variants have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible.
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