477 - Clinical Manifestations and Genetic Mutations of Carbonic Anhydrase II Deficiency in a Consanguineous Population

Publication Number: 2465.477

Razan AlAttas, The Hospital for Sick Children, Riyadh, Ar Riyad, Saudi Arabia; Raghad Alhuthil, King Faisal Specialist Hospital and Research Centre, Riyadh, Ar Riyad, Saudi Arabia; Sarah Y. Alharthi, KFSH&RC, Riyadh, Ar Riyad, Saudi Arabia; Rand M. Almofreh, KFSH&RC, riyadh, Ar Riyad, Saudi Arabia; Afaf Alsagheir, King Faisal Specialist Hospital and Research Centre, Riyadh, Ar Riyad, Saudi Arabia; Abdulla Ehlayel, KFSHRC, Riyadh, Ar Riyad, Saudi Arabia

Background: Carbonic anhydrase II deficiency (CA2D) is a rare autosomal recessive disorder caused by mutations in the CA2 gene. Classical presentations include osteopetrosis, renal tubular acidosis (RTA), and intracranial calcifications. It may also involve developmental, neurological, and skeletal complications. Limited data is available in the literature on patients with this clinical condition.

Objective: To describe the clinical features, complications, and genetic variants among Saudi patients with CA2D.

Design/Methods: We retrospectively analyzed 44 patients with genetically confirmed CA2D followed at King Faisal Specialist Hospital and Research Center (KFSHRC), a major tertiary referral center in the country. Demographic, clinical, anthropometric, biochemical, radiologic, and genetic data were reviewed and recorded. Ethical approval for the study was obtained (KFSHRC Reference No. 2251224).

Results: Of the cohort, 54.5% were female, all Saudi nationals, and 34.1% had documented consanguinity. The median age at presentation was 7 years (IQR 2–15.5). The most frequent referral reasons were distal RTA (75%) and intracranial calcifications (65.9%). All tested patients were homozygous for the CA2 gene mutation. Among the 11 patients whose genetic testing reported a specific mutation variant, the predominant mutation was the splice-site variant c.232+1G>A (91%), while one patient carried the c.48+1G>A variant. Growth remained subnormal throughout follow-up (final height SDS -2.46, weight SDS -2.49). Electrolytes reflected chronic hyperchloremic metabolic acidosis, while creatinine and minerals remained within or near normal ranges. Neurological (58.5%) and skeletal (61.4%) complications were common, including developmental delay, fractures, and dental abnormalities.

Conclusion(s): To our knowledge, this is the largest cohort of genetically confirmed CA2D reported to date. The c.232+1G>A splice-site mutation predominates in Saudi patients, underscoring a regional founder effect. Persistent growth failure and multi-system complications highlight the need for early diagnosis, multidisciplinary management, and genetic counseling.

Table 1: Demographics & Referral (n=44)
(Table 1) CA2 Abstract.pdf

Table 2: Anthropometrics & Labs
(Table 2) CA2 Abstract.pdf

Table 3: Complications, Management & Imaging
(Table 3) CA2 Abstract.pdf