Clinical and molecular spectrum of patients with methylmalonic acidemia and homocysteinemia complicated by cardiovascular manifestations.

Background: To investigate the clinical characteristics, treatment response, and prognosis of patients with methylmalonic acidemia (MMA) and homocysteinemia complicated by cardiovascular manifestations and to raise awareness regarding MMA and homocysteinemia.

Methods: A total of 16 children diagnosed with MMA and homocysteinemia with cardiovascular manifestations who were admitted to the Department of Pediatrics of the Second Hospital of Hebei Medical University from June 2018 to October 2024 were retrospectively analyzed.

Results: All 16 patients had varying degrees of neurological manifestations, and all had cardiovascular manifestations, 3 patients were diagnosed with MMA and homocysteinemia by newborn screening and received conventional treatment, the remaining 13 patients had nausea, vomiting, anemia, recurrent pneumonitis, respiratory distress, and lethargy as their first symptoms. Cardiovascular complications were found between the ages of 2 months and 12 years, with 9 patients having pulmonary hypertension, 7 having hypertension, and 5 having non-compaction of ventricular myocardium. Fourteen of these cases were confirmed to have CblC-type methylmalonic acidemia caused by mutations in the MMACHC gene by genetic testing. The most common mutations were c.80A > G (p.Q27R) (8 cases) and c.609G > A (p.W203X) (8 cases).

Conclusion: Cardiovascular manifestation is uncommon in patients with MMA and homocysteinemia, but it is usually critical cause of death. When unexplained pulmonary hypertension or hypertension occurs, MMA and homocysteinemia should be suspected, especially when accompanied by manifestations of other systems.