Carbonic anhydrase II deficiency in three unrelated Japanese patients

Abstract

Three Japanese patients with carbonic anhydrase II (CAII) deficiency from three families were described. The parents of one patient were unrelated, the parents of each of the other two patients were first cousins. All the patients had renal tubular acidosis, osteopetrosis, symmetrical cerebral calcification and mental retardation. They exhibited poor activity and poor appetite in the neonatal period, and then developed psychomotor retardation. Two of them were diagnosed as having osteopetrosis at 10 months and 36 years of age, respectively, and the other as having osteomalacia at 28 years of age. All patients had recurrent episodes of muscle weakness. The CAII enzyme activity and protein levels in red blood cells in each of the three patients were deficient. Their parents exhibited approximately 50% normal levels of CAII activity and protein. This is the first report of patients with CAII deficiency in the Japanese population.

Unfolding a Folding Disease: Folding, Misfolding and Aggregation of the Marble Brain Syndrome-associated Mutant H107Y of Human Carbonic Anhydrase II

“…It is worth pointing out that HCA II generates cerebrospinal fluid (CSF) in the choroid plexus of the brain; however, the mechanism of cerebral calcification in MBS is unclear. 13 It is therefore possible that protein aggregate accumulation in the cytosol or aggregation in combination with the loss-of-function of HCA II can induce pathological mechanisms.…”

“…12 HCA II is known to generate cerebrospinal fluid (CSF) in the choroid plexus of the brain. Nevertheless, the mechanism of cerebral calcification is unclear 13 but is a manifest of the disease that gave it its original name, marble brain syndrome. Growth retardation seems to be the result of the osteopetrosis on bone elongation, whereas RTA is affecting the general health.…”

“…The parents appear normal, indicating that only half the normal concentration of HCA II is necessary to maintain the important functions. 13 Eleven different mutations in the HCA II gene have been reported to cause CADS. 14,15 In one of them, His107 is replaced with Tyr.…”

Carbonic anhydrase II deficiency in a Japanese patient produced by a nonsense mutation (TAT →TAG) at Tyr-40 in exon 2, (Y40X)

“…This syndrome has not previously been reported in the Japanese population except three patients including this patient (Aramaki et al, 1993). All of three patients were habitants in the northern part of Kyushu islands.…”

Nephrocalcinosis and urolithiasis in carbonic anhydrase II deficiency syndrome

“…The majority of patients come from North Africa and the Middle East, with nearly 75% being of Arabic descent. The disease was ®rst reported from Asia in 1993 when three unrelated patients from Japan were described [2]. The locus for the CA II gene has been mapped to chromosome 8q22 [12].…”