Growth and growth hormone therapy in subjects with mulibrey nanism.

OBJECTIVES: Mulibrey nanism is a monogenic disorder with prenatal-onset growth restriction, mild dysmorphic features, and a strong tendency for insulin resistance but no major neurologic handicap. Growth hormone therapy has been shown to promote short-term growth in children born small for gestational age, but the experience with long-term therapy is insufficient. Growth in patients with mulibrey nanism has not been analyzed previously in detail.
METHODS: We evaluated the natural growth pattern and long-term impact of growth hormone treatment in the largest cohort of subjects with mulibrey nanism to date. The study included 72 living subjects followed up to 30 years. Thirty (18 female) were treated with recombinant human growth hormone for a median period of 5.7 years. Patients were reviewed at baseline and every 6 to 12 months during the therapy. Evaluation included assessment of height, weight, and pubertal status and laboratory analyses. Glucose metabolism was evaluated by oral glucose-tolerance test.
RESULTS: The patients were born small for gestational age with immature craniofacial features. They experienced a continuous deceleration in height (median decrement of 1.1 SDS) and weight for height (median reduction of 17%) in infancy followed by an incomplete catch-up growth lasting up to school age. The final adult height averaged 136 cm in girls and 150 cm in boys. Growth hormone treatment improved the prepubertal growth but had only little impact on adult height (+5 cm). The treated subjects showed earlier bone maturation and growth arrest but not a significant increase in insulin resistance. On the contrary, the subjects who were treated with growth hormone were slimmer and had less metabolic syndrome as young adults.
CONCLUSIONS: The patients with mulibrey nanism showed a distinct postnatal growth pattern. The growth hormone treatment was safe and induced a good short-term effect, but the impact on the adult height remained modest.