Sly W S, Whyte M P, Sundaram V, Tashian R E, Hewett-Emmett D, Guibaud P, Vainsel M, Baluarte H J, Gruskin A, Al-Mosawi M
N Engl J Med. 1985 Jul 18;313(3):139-45. doi: 10.1056/NEJM198507183130302.
Osteopetrosis with renal tubular acidosis and cerebral calcification was identified as a recessively inherited syndrome in 1972. In 1983, we reported a deficiency of carbonic anhydrase II, one of the isozymes of carbonic anhydrase, in three sisters with this disorder. We now describe our study of 18 similarly affected patients with this syndrome in 11 unrelated families of different geographic and ethnic origins. Virtual absence of the carbonic anhydrase II peak on high-performance liquid chromatography, of the esterase and carbon dioxide hydratase activities of carbonic anhydrase II, and of immunoprecipitable isozyme II was demonstrated on extracts of erythrocyte hemolysates from all patients studied. Reduced levels of isozyme II were found in obligate heterozygotes. These observations demonstrate the generality of the findings that we reported earlier in one family and provide further evidence that a deficiency of carbonic anhydrase II is the enzymatic basis for the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. We also summarize the clinical findings in these families, propose mechanisms by which a deficiency of carbonic anhydrase II could produce this metabolic disorder of bone, kidney, and brain, and discuss the clinical evidence for genetic heterogeneity in patients from different kindreds with this inborn error of metabolism.
1972年，骨硬化症伴肾小管酸中毒和脑钙化被确认为一种隐性遗传综合征。1983年，我们报道了3名患有这种疾病的姐妹中碳酸酐酶II（碳酸酐酶的同工酶之一）缺乏。我们现在描述我们对来自11个不同地理和种族起源的无关家庭中18名患有类似综合征患者的研究。在所有研究患者的红细胞溶血产物提取物中，通过高效液相色谱法证实碳酸酐酶II峰实际上不存在，碳酸酐酶II的酯酶和二氧化碳水合酶活性以及可免疫沉淀的同工酶II也不存在。在必然杂合子中发现同工酶II水平降低。这些观察结果证明了我们之前在一个家庭中报道的发现具有普遍性，并进一步证明碳酸酐酶II缺乏是骨硬化症伴肾小管酸中毒和脑钙化的常染色体隐性综合征的酶学基础。我们还总结了这些家庭中的临床发现，提出了碳酸酐酶II缺乏可能导致这种骨骼、肾脏和脑部代谢紊乱的机制，并讨论了来自不同家族的患有这种先天性代谢错误的患者中基因异质性的临床证据。
