The correlation of intracranial parenchymal calcium score and the severity of neurological clinical presentation in carbonic anhydrase deficiency type 2

Basma AlFaris; Fahad B AlBader; Rawan AlSheikh; Fahad A Bashiri; Muddathir H Hamad; Amal Kentab; Malak Alghamdi

doi:10.1016/j.braindev.2024.104309

The correlation of intracranial parenchymal calcium score and the severity of neurological clinical presentation in carbonic anhydrase deficiency type 2

Brain Dev. 2024 Dec 11;47(1):104309. doi: 10.1016/j.braindev.2024.104309. Online ahead of print.

Authors

Basma AlFaris¹, Fahad B AlBader², Rawan AlSheikh³, Fahad A Bashiri⁴, Muddathir H Hamad⁵, Amal Kentab⁶, Malak Alghamdi⁷

Affiliations

¹ Division of Pediatric Neurology, Department of Pediatrics, King Fahad Medical City, Riyadh, Saudi Arabia. Electronic address: [email protected].
² Department of Radiology and Medical Imaging, King Saud University Medical City, College of Medicine, King Saud University, Riyadh, Saudi Arabia. Electronic address: [email protected].
³ Division of Pediatric Neurology, Department of Pediatrics, King Saud Medical City, Riyadh, Saudi Arabia. Electronic address: [email protected].
⁴ Division of Pediatric Neurology, Department of Pediatrics, King Saud University Medical City, Riyadh, Saudi Arabia; Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia. Electronic address: [email protected].
⁵ Division of Pediatric Neurology, Department of Pediatrics, King Saud University Medical City, Riyadh, Saudi Arabia; Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia. Electronic address: [email protected].
⁶ Division of Pediatric Neurology, Department of Pediatrics, King Saud University Medical City, Riyadh, Saudi Arabia; Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia. Electronic address: [email protected].
⁷ Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Division of Medical Genetics, Department of Pediatrics, King Saud University Medical City, Riyadh, Saudi Arabia. Electronic address: [email protected].

PMID: 39667299
DOI: 10.1016/j.braindev.2024.104309

Abstract

Background: Carbonic anhydrase type II deficiency (CAII-D) syndrome is a rare autosomal recessive genetic disorder characterized by osteopetrosis, renal tubular acidosis, and brain calcifications. Understanding the clinical and radiological features of CAII-D is key to effective management.

Aim: This study aimed to comprehensively analyze and measure intracranial parenchymal calcium score in pediatric CAII-D in relation to the severity of neurological clinical presentation.

Methods: A retrospective chart review at King Saud University Medical City included pediatric CAII-D patients diagnosed between June 2015 and December 2022. Study variables included age, gender, genetic results, developmental status, developmental quotient (DQ), CT findings, optic canal diameter, intracranial calcium score, and neuropsychiatric symptoms.

Results: Ten CAII-D patients, median age 10.5 years, were included. Most patients displayed homozygous pathogenic CA2 gene variants. For neurodevelopmental symptoms, 60.0 % of patients presented with global developmental delay, 20.0 % had intellectual disability, and the remaining 20.0 % had normal development. The median DQ score was 63.50, with 80.0 % categorized as delayed. Neuropsychiatric disorders were present in 20.0 %. Optic nerve atrophy was observed in 22.2 %, while brain calcifications were present in 70.0 % of cases. Correlation analysis revealed no significant associations between intracranial parenchymal calcium score and age, DQ score, or optic canal diameter. Neurodevelopmental symptoms, neuropsychiatric symptoms, and DQ were not associated with intracranial parenchymal calcium score.

Conclusion: Intraparenchymal calcifications in CAII-D are common but unrelated to developmental delay and neuropsychiatric symptoms, suggesting complex pathophysiology. Follow-up brain imaging may not aid in prognosis or severity assessment, highlighting the need for further research.

Keywords: Calcium metabolism; Carbonic anhydrase deficiency type 2; Disease severity; Intracranial calcification; Neurological disorders; Osteopetrosis.