Renal Tubular Acidosis, Osteopetrosis, and Cerebral Calcification: A Rare Syndrome Caused by Carbonic Anhydrase II Deficiency

A 7‐year, 10‐month‐old boy, product of a consanguineous marriage, presented with short stature and a recent fracture of left forearm following a trivial trauma. There was no significant family history. His height was 103 cm (−3.7 standard deviation) [Table 1]. He had dysmorphic facies such as prominent forehead, thick lower lip, and blue sclera. He had 24 teeth; his temporary teeth had not shed yet. There were no features of rickets or tetany. On investigation, he had normal complete blood count and liver and kidney function tests. Investigations also revealed hypocalcemia, systemic acidosis, and alkaline urine (systemic pH of 7.21 and urine pH of 6.5 in the presence of normal renal functions) [Table 1]. Radiological survey showed hyperdense bones in forearm and lower limbs with a fracture in the left forearm [Figure 1]. Non‐contrast computed tomography head showed bilateral basal ganglia calcification. Thus, in view of classical triad of osteopetrosis, RTA, and cerebral calcification, a diagnosis of carbonic anhydrase II deficiency was considered. Sanjad‐Sakati syndrome, Kenny‐Caffey syndrome, and Kirk‐Richardson syndrome may present with a similar phenotype, these usually are not associated with RTA. Carbonic anhydrase II deficiency is a rare disease with varied presentation and most commonly presents as a triad of RTA, osteopetrosis, and cerebral calcification.[1] Other manifestations include short stature, mental retardation, anemia with ovalocytosis, retinal changes, and multiple cranial nerve palsies.[2] These diverse manifestations are due to omnipresent location of the enzyme, and the degree of involvement depends on the extent of enzyme expression in a particular organ. RTA is usually a mixed type with features of both proximal and distal types.[3] Carbonic anhydrase II has important role in both proximal and distal tubules in kidney for generation of H+ and HCO3 −; thus, features of both proximal and distal RTA are found. Osteopetrosis results from decreased activity of osteoclasts.[4] Cerebral calcifications usually develop after 5 years of age and are more common in basal ganglia region and sometimes in periventricular subcortical white matter. Exact mechanism of the development of cerebral calcifications is not clear, but carbonic anhydrase II has a definite role in cerebrospinal fluid secretion.[2]