Karlberg Niklas, Jalanko Hannu, Lipsanen-Nyman Marita
Hospital for Children and Adolescents, Department of Pediatric Endocrinology, University of Helsinki, 00290 Helsinki, Finland.
Pediatrics. 2007 Jul;120(1):e102-11. doi: 10.1542/peds.2006-2686. Epub 2007 Jun 4.
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.
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.
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.
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.
穆利布雷侏儒症是一种单基因疾病，具有产前生长受限、轻度畸形特征以及强烈的胰岛素抵抗倾向，但无严重神经功能障碍。生长激素治疗已被证明可促进小于胎龄儿出生后的短期生长，但长期治疗的经验不足。此前尚未对穆利布雷侏儒症患者的生长情况进行详细分析。
我们评估了迄今为止最大规模的穆利布雷侏儒症患者队列的自然生长模式以及生长激素治疗的长期影响。该研究纳入了72名存活受试者，随访时间长达30年。其中30名（18名女性）接受了重组人生长激素治疗，中位治疗时间为5.7年。在治疗期间，对患者进行基线评估以及每6至12个月的复查。评估内容包括身高、体重、青春期状态评估以及实验室分析。通过口服葡萄糖耐量试验评估葡萄糖代谢情况。
这些患者出生时为小于胎龄儿，颅面部特征不成熟。在婴儿期，他们的身高持续减速（中位下降1.1标准差分值），身高别体重也下降（中位降低17%），随后是持续至学龄期的不完全追赶生长。成年女性最终平均身高为136厘米，成年男性为150厘米。生长激素治疗改善了青春期前的生长，但对成年身高的影响很小（增加5厘米）。接受治疗的受试者骨成熟和生长停滞较早，但胰岛素抵抗没有显著增加。相反，接受生长激素治疗的受试者在年轻时更苗条，代谢综合征较少。
穆利布雷侏儒症患者呈现出独特的出生后生长模式。生长激素治疗安全且能产生良好的短期效果，但对成年身高的影响仍然有限。
