Growth outcomes following recombinant human growth hormone therapy in Zhu-Tokita-Takenouchi-Kim syndrome.
This case shows a significant growth response to rhGH therapy in a child with ZTTK syndrome, despite normal GH levels.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study reports on a female child with Zhu-Tokita-Takenouchi-Kim syndrome treated with recombinant human growth hormone (rhGH) at a dose of 0.035 mg/kg/day. Following treatment, there was a greater than 50% increase in height velocity from baseline over a two-year period. No adverse effects were observed during the treatment.
Abstract
Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is a rare multisystem developmental disorder caused by heterozygous pathogenic variants in SON. Short stature is common, but data on endocrine function and response to recombinant human growth hormone (rhGH) are limited. We describe a female child with genetically confirmed ZTTK syndrome presenting with profound proportionate short stature, hypotonia, and developmental delay. Insulin-like growth factor 1 (IGF-1) of 91 ng/mL (Systeme international [SI]: 11.9 nmol/L; reference range, 33.6-170.5 ng/mL [SI: 4.4-22.3 nmol/L]) was normal, and peak growth hormone (GH) concentration on arginine stimulation testing was 7.2 ng/mL (SI: 21.6 mIU/L], above the UK diagnostic cutoff for GH deficiency (<6.7 ng/mL [SI: <20.1 mIU/L]). Given severely impaired linear growth and declining height velocity, a monitored trial of rhGH was initiated. Treatment with rhGH (0.035 mg/kg/day) resulted in >50% increase in height velocity from baseline (4.3-7.2 cm/year), suggesting a good response to rhGH, with sustained improvement over 2 years (height standard deviation score -4.16 to -3.40). Insulin-like growth factor 1, thyroid function, glucose, and glycated hemoglobin A1c remained normal. No adverse effects were observed. This case demonstrates a clinically significant growth response to rhGH in ZTTK syndrome despite absence of biochemical GH deficiency, supporting a supervised 12-month therapeutic trial.
Background
Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome is a rare genetic disorder characterized by short stature and developmental delays. Previous literature has indicated that endocrine function in ZTTK syndrome is not well understood, particularly regarding the response to growth hormone therapy. This study is significant as it explores the effects of recombinant human growth hormone (rhGH) in a patient with ZTTK syndrome, providing insight into potential treatment options for similar cases.
Methods
This is a case report describing a female child with genetically confirmed ZTTK syndrome. The patient received rhGH at a dose of 0.035 mg/kg/day for a duration of 2 years. Primary outcome measures included height velocity and height standard deviation scores, with secondary measures assessing IGF-1 levels and other metabolic parameters.
Results
The primary endpoint showed a height velocity increase from 4.3 cm/year to 7.2 cm/year, indicating a >50% improvement. The height standard deviation score improved from -4.16 to -3.40 over the treatment period. No adverse effects were reported, and metabolic parameters remained within normal ranges.
Interpretation
The findings suggest that rhGH therapy may elicit a clinically significant growth response in patients with ZTTK syndrome, even in the absence of biochemical GH deficiency. However, the effect size, while statistically significant, may not be generalizable due to the limitations of a single case report. The absence of a control group and the small sample size further limit the conclusions that can be drawn from this study.
Key findings
- IGF-1 of 91 ng/mL, normal range 33.6-170.5 ng/mL.
- Peak GH concentration of 7.2 ng/mL, above cutoff of <6.7 ng/mL.
- >50% increase in height velocity from baseline (4.3-7.2 cm/year).
- Height standard deviation score improved from -4.16 to -3.40 over 2 years.
Limitations
- Single case report limits generalizability.
- No control group.
- Small sample size.
- Absence of biochemical GH deficiency complicates interpretation.