Neuroimaging Findings in Carbonic Anhydrase VA Deficiency: A Case Series Highlighting Diagnostic and Prognostic Patterns in a Potentially Reversible Mitochondrial Dysfunction.

BACKGROUND AND PURPOSE: Imaging characteristics of the secondary urea cycle disorder caused by carbonic anhydrase VA (CA-VA) deficiency remain poorly understood. This study aimed to evaluate the neuroimaging features associated with CA-VA deficiency through a collaborative multicenter investigation.

MATERIALS AND

METHODS

A retrospective, longitudinal study with confirmed CA5A variants at 5 large centers was performed. MR studies were qualitatively reviewed according to a standardized reporting form at initial and follow-up MRI.

RESULTS

A total of 9 patients with CA-VA deficiency were included, 6 of whom were girls. The median age at symptom onset was 3 days (interquartile range: 2.5-48.5 days), and the median interval between symptom onset and brain MRI was 7 days. Seven patients (77%) had experienced a single metabolic crisis so far. A favorable clinical outcome, defined as the absence of notable neurologic impairment was observed in 5 patients (55.5%), while 4 (44.4%) exhibited moderate to severe neurologic long-term impairment. All patients demonstrated brain imaging abnormalities. In the favorable-outcome group (FOG), imaging findings demonstrated a urea cycle disorder (UCD)-like pattern, with selective involvement of the cortical and juxtacortical regions of the insular/peri-insular area, the Sylvian/peri-Sylvian fissures, and the perirolandic cortex. In contrast, the unfavorable-outcome group (UOG) exhibited either more extensive involvement of the aforementioned regions, extending to the thalamus, basal ganglia, and brainstem. Follow-up MRI was available for 3 patients; 2 showed near-complete resolution of brain abnormalities (FOG), while 1 displayed relatively extensive chronic gliotic changes (UOG).

CONCLUSIONS

MRI plays a key role in the early diagnosis of CA-VA deficiency, because brain abnormalities are expected and often exhibit features suggestive of an underlying UCD. Furthermore, neuroimaging may serve as a valuable prognostic marker, directly impacting clinical decision-making, management, and follow-up strategies.