Clinical and molecular heterogeneity in carbonic anhydrase II deficiency and prenatal diagnosis in an Italian family,☆☆,

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Abstract

Carbonic anhydrase (CA) II deficiency is characterized by osteopetrosis, renal tubular acidosis, cerebral calcification, and usually severe mental retardation. We describe an Italian boy with this disease whose mental retardation was relatively mild and whose renal tubular acidosis had only a distal component. A novel mutation of a gt > tt change of splice donor site at the 5' end of intron 6 was demonstrated. Comparison of this patient with two previous Italian families with different mutations illustrates the clinical and molecular heterogeneity of this disease. The identification of the mutation in this family provided the opportunity for prenatal diagnosis in a subsequent pregnancy. (J Pediatr 1998;132:717-20)

Section snippets

CASE REPORT

A. M. was born to a 24-year-old woman after an uneventful term pregnancy and delivery. His birth weight was 2800 gm. His healthy parents were first cousins. Failure to thrive and hepatosplenomegaly were present in the first months of life, and soon afterward he exhibited delayed psychomotor development.

At the age of 3 years his weight was 11 kg (<5th percentile), his height was 85 cm (<5th percentile), and his head circumference was 49 cm (25 to 50th percentile). He had a prominent forehead and

METHODS

The levels of CA II in erythrocyte lysates were quantitated by measuring CO2 hydratase activity in the presence and absence of sodium iodide and bromopyruvic acid, both of which selectively inhibit CA I.7 DNA samples from the parents and the patient were isolated from leukocytes.8 Chorionic villi sampling was performed with the mother's informed consent after 8 weeks of a subsequent pregnancy. DNA was isolated by standard procedures. Individual exons and surrounding intronic sequences were

RESULTS AND DISCUSSION

The proband in this study was given the diagnosis of CA II deficient at the age of 3 years by the virtual absence of CA II activity in his erythrocyte lysate and the half-normal level of CA II activity in both parents. The mother was counseled that she had a 25% risk of recurrence in future pregnancies, and she chose to defer pregnancy. After subsequent cloning of the CA II cDNA and genomic sequences made prenatal diagnosis possible,2, 3 the mother of the proband became pregnant.

Direct

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From the Department of Pediatrics, Catanzaro, University of Reggio Calabria, Italy, and Edward A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, St. Louis, Missouri.

☆☆

Reprint requests: Pietro Strisciuglio, MD, Associate Professor of Pediatrics, Department of Pediatrics Faculty of Medicine, University of Reggio Calabria, c/o Ospedale “A. Pugliese” Via Pio X, 88100, Catanzaro, Italy.

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