Clinical features and treatment of methylmalonic acidemia complicated with Dandy-Walker syndrome: a report of four cases and review of literature.

PURPOSE

The clinical characteristics and treatment of the rare methylmalonic academia (MMA) with Dandy-Walker syndrome (DWS) are still unclear. This study aims to provide insights into this rare pediatric condition.

METHODS

A retrospective analysis was conducted on MMA cases from our pediatric ICU database (2006-2021), identifying those with concurrent DWS. Onset age, clinical features, genetic types, treatment, and prognosis were analyzed. MMA diagnosis was confirmed via blood and urine tandem mass spectrometry, while DWS was diagnosed through cranial MRI. Follow-up was conducted via phone or outpatient visits.

RESULTS

Of 198 MMA cases, four (three males, one female) had DWS, with an average onset age of 38 days (range: 4-60 days). Vomiting (3/4) was the most common symptom. Two patients had a small head circumference. Blood homocysteine levels ranged from 130.8-187.3 µmol/L, and urine MMA levels ranged from 24.5-236.1 mmol/mol·creatinine. Blood C3 and C3/C2 ratios were elevated in all patients. MRI showed cerebellar vermis dysplasia and fourth ventricle cystic dilatation. All patients received treatment with medications and specialized formula. Case 3 developed elevated intracranial pressure (ICP) and died from multi-organ failure. Cases 1, 2, and 4 had ventriculoperitoneal shunt (VPS) for ICP. Case 1 died of respiratory failure 10 months post-surgery, Case 2 from severe pneumonia 96 months post-surgery, and Case 4 remained stable at 32 months follow-up.

CONCLUSION

DWS may present as a clinical manifestation of MMA, often with early onset and severe symptoms. Elevated ICP and hydrocephalus are common, and VPS may effectively alleviate ICP and improve prognosis.

© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.