6 GROWTH HORMONE GENE DELETION WITHOUT GROWTH ARREST

Abstract

Isolated growth hormone deficiency type 1A (IGHD 1A) is caused by deletion of the hGH-N gene. As described in Swiss pedigrees, antibody development and growth arrest complicate hGH treatment. We used restriction endonuclease analysis to detect hGH-N deletion among Oriental Jewish children with IGHD and then examined responses to hGH treatment. Patients in 4 families were products of consanguinous matings. They were homozygous for deletion of the hGH-N gene as shown by absence of characteristic, hybridizing, Bam HI and Hinc II fragments. Abnormal size Hind III fragments indicated deletions of 7.5 kb. Polymorphic Bgl II and Msp I patterns differed in patient 4, suggesting that at least 2 different events had produced deletions of similar size. Growth data are shown below: Despite extreme pre-Rx height deficits, growth responses to hGH treatment were good. Antibodies did not appear or did not impede growth. We conclude that factors other than gene deletion contribute to formation of blocking antibodies to hGH. Growth failure during treatment is not a sensitive marker for IGHD 1A. Diagnosis requires study of patients' GH genes.