OBJECTIVE

To analyze the clinical characteristics of patients with hydrocephalus secondary to cobalamin C (cblC) deficiency and to discuss the optimal strategies for assessing and treating such patients by performing clinical and laboratory studies in 70 patients.

METHODS

A total of 1,211 patients were clinically diagnosed with methylmalonic acidemia (MMA) from 1998 to 2019. Among them, cblC deficiency was confirmed in 70 patients with hydrocephalus by brain imaging and biochemical and genetic analysis.

RESULTS

Of the 70 patients, 67 (95.7%) had early-onset MMA and homocystinuria. The patients typically had high blood propionylcarnitine and total homocysteine, low methionine, and methylmalonic aciduria. Signs of intracranial hypertension were relatively rare. We measured ventricular dilatation early in the disease by cranial ultrasound and MRI and/or CT. Eighteen different mutations, including 4 novel mutations (c.427C>T, c.568insT, c.599G>A, and c.615C>A), were identified biallelically in all 70 patients. c.609G>A was the most frequent mutation, followed by c.658_660del, c.217C>T, and c.567dupT. Three cases were diagnosed by postmortem study. Metabolic therapy, including cobalamin injections supplemented with oral l-carnitine and betaine, was administered in the remaining 67 cases. A ventriculoperitoneal shunt was performed in 36 cases. During the follow-up, psychomotor development, nystagmus, impaired vision, and sunset eyes improved gradually.

CONCLUSION

Hydrocephalus is a severe condition with several different causes. In this study, ventriculomegaly was found in 70 patients with cblC deficiency. Early diagnosis, etiologic treatment, and prompt surgical intervention are crucial to improve the prognosis of patients.