Hydrocephalus Caused by Methylmalonic Acidemia: Clinical Characteristics, Optimal Timing of Surgical Intervention and Health-Related Quality of Life.

Abstract

Hydrocephalus is a rare and potentially fatal complication of methylmalonic acidemia (MMA) and is associated with a poor prognosis, requiring prompt clinical decision making. The aim of our study was to evaluate the clinical characteristics and quality of life of infants with hydrocephalus caused by MMA and to determine the optimal timing of surgery. This is a retrospective observational study. We reviewed 77 MMA-related hydrocephalus cases from 1671 hydrocephalus patients admitted between June 2012 and March 2022. Data collected included clinical characteristics, surgical data, and health-related quality of life assessed using the Pediatric Quality of Life Inventory (PedsQL™) 4.0 generic core scales. The most common clinical manifestations were developmental retardation, poor appetite, and altered consciousness. The most frequent mutation was c.609G>A in MMACHC gene (70%). Sixty-six patients (85.7%) underwent ventriculoperitoneal shunting with higher Evans index than the non-VPS group ( P < .001). An Evans index cutoff point of 0.45 was identified. The non-VPS group scored better on all PedsQL™ domains. Of the 66 cases in the ventriculoperitoneal shunting group, 19 (24.7%) needed revision surgery. They had a shorter duration of drug treatment ( P = .002) and underwent surgery at a younger age ( P = .049) than those in the nonrevision group. Optimal cutoff points were duration of drug treatment >1 month and age of surgical treatment >4.5 months. The revision group had lower psychosocial health and school functional scores. Our study provides insights into the clinical profile and health-related quality of life of patients with hydrocephalus caused by MMA. Those with severe hydrocephalus had lower PedsQL™ scores and need surgery. The optimal timing for surgery in these patients is Evans index >0.45, duration of drug treatment >1 month, and age of surgical treatment >4.5 months after birth to reduce surgical complications and improve quality of life.