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 five 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 nine patients with CA-VA deficiency were included, six of whom were female. The median age at symptom onset was 3 days (interquartile range [IQR]: 2.5-48.5 days), and the median interval between symptom onset and brain MRI was 7 days. Seven patients (77%) experienced a single metabolic crisis so far. A favorable clinical outcome, defined as the absence of significant neurological impairment was observed in five patients (55.5%), while four (44.4%) exhibited moderate to severe neurological longterm impairment. All patients demonstrated brain imaging abnormalities. In the favorable-outcome group, imaging findings demonstrated a urea cycle disorder-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 exhibited either more extensive involvement of the aforementioned regions-extending to the thalamus, basal ganglia, and brainstem. Follow-up MRI was available for three patients: two of them showed near-complete resolution of brain abnormalities (favorable outcome group), while one displayed relatively extensive chronic gliotic changes (unfavorable outcome group).

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

Abbreviations: CA-VA＝ Carbonic Anhydrase VA; CA-VB＝ Carbonic Anhydrase VB; FOG＝ Favorable-outcome group; UOG＝ Unfavorable-outcome group; UCD＝ Urea cycle disorders.