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  • The carbonic anhydrase II deficiency syndrome is an autosomal recessive disorder that produces osteopetrosis, renal tubular acidosis, and cerebral calcification. Other features include mental retardation (seen in over 90 percent of reported cases), growth failure, and dental malocclusion.

  • Complications of osteopetrosis include increased susceptibility to fractures (which do, however, heal normally) and cranial nerve compression symptoms. Anemia and other hematologic manifestations of osteopetrosis are absent.

  • The renal tubular acidosis is usually a mixed type. A distal component is evident from inability to acidify the urine, and a proximal component is evident from a lowered transport maximum for bicarbonate. Impaired respiratory compensation for the metabolic acidosis has recently been recognized.

  • Over 110 patients have been reported, all of who have a quantitative deficiency of carbonic anhydrase II activity and immunoreactivity in erythrocytes. Heterozygous carriers can be identified by simple tests. Structural gene mutations have been identified in the CA II gene of every patient analyzed genetically.

  • The carbonic anhydrase II gene is 20 kb, contains seven exons, and maps to chromosome 8q22. Sixteen distinct mutations have been identified in 110 reported patients. Nearly 65 percent of affected patients are homozygous for a splice junction mutation at the 5′ end of exon 2. Because of its prevalence among families of Arabic descent from Kuwait, Saudi Arabia, and North Africa, this mutation has been designated the “Arabic mutation.” The second recurrent mutation, a frameshift in exon 7, is most prevalent in Caribbean Hispanic populations. The third recurrent mutation is His 107 → Tyr, the first reported mutation. This mutation is due to a C → T transition in exon 3 and has been found in Belgian, Italian, Japanese, and American patients. The three affected sisters in the American family were compound heterozygotes, having inherited the His 107 → Tyr mutation from their mother and a splice acceptor mutation in the 3′ end of intron 5 from their father. The remaining 13 mutations are private mutations seen in single families and all are detectable by PCR amplification and direct sequencing of various exons. Thus, PCR-based diagnosis and prenatal diagnosis are available for the 16 known mutations.

  • Symptoms of metabolic acidosis improve with treatment, but no specific treatment is available.


Albers-Schönberg first described osteopetrosis (marble bone disease) in 1904.1 Subsequently, over 300 cases have been reported.2 Among these, two principal types were distinguished. An autosomal dominant form was called the adult, benign form because of the relatively few symptoms and the benign course, which is compatible with normal life span. The diagnosis is often made incidentally in adults evaluated for other complaints. At the other extreme is the clinically severe, autosomal recessive form which has its onset in infancy and produces anemia, leukopenia, hepatomegaly, failure to thrive, cranial nerve symptoms, and early death. This form is often referred to as the infantile, malignant, or lethal form. Beighton and colleagues have pointed out the existence of ...

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