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An immunologically anomalous but considerably bioactive growth hormone produced by a novel GH1 mutation (p.D116E)

S Dateki, Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo, Japan
K Hizukuri, Pediatrics, Kagoshima University School of Medicine, Kagoshima, Japan
T Tanaka, Tanaka Growth Clinic, Tokyo, Japan
N Katsumata, Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo, Japan
P Katavetin, Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo, Japan
T Ogata, Endocrinology and Metabolism, National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan

Correspondence: Tsutomu Ogata, Email: tomogata{at}nch.go.jp

Context: Although growth hormone (GH) values measured by an immunoassay usually reflect GH bioactivities, discrepancy exists between immunoactivity and bioactivity in a rare condition known as "bioinactive GH".

Objective: To report an immunologically anomalous but considerably bioactive GH.

Methods: We performed mutational and functional analyses of GH1 in a seven-year-old Japanese boy with short stature (-3.0 SD) in whom serum GH values measured with a Tosoh immunoassay kit were all undetectable in three provocation tests, whereas urine GH value measured with a Hitachi immunoassay kit was within the normal range. Serum insulin-like growth factor-1 was at a low-normal range, and insulin-like growth factor binding protein-3 was below the normal range.

Results: Mutation analysis showed a missense mutation (p.D116E) of paternal origin and a frameshift mutation (p.Q68fsX106) of maternal origin. Genotype-phenotype correlations in this family and in vitro functional studies indicated that the p.D116E-GH was immeasurable with the Tosoh kit but was measurable, though may not be precise, with a Daiichi kit, and had a reduced in vivo bioactivity. The p.Q68fsX106 yielded no GH protein.

Conclusions: The results suggest that the p.D116E affects the GH epitope primarily recognized by the Tosoh kit but not by the Hitachi or the Daiichi kits, thereby producing an immunologically anomalous but considerably bioactive GH. The presence of such a hormone discordant for immunoactivity and bioactivity should be kept in mind, to allow for an appropriate assessment of endocrine data.