Growth outcomes following recombinant human growth hormone therapy in Zhu-Tokita-Takenouchi-Kim syndrome.
This case demonstrates a significant growth response to rhGH therapy in a child with ZTTK syndrome, despite normal GH levels, highlighting the need for supervised trials in similar cases.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This case report describes a female child with Zhu-Tokita-Takenouchi-Kim syndrome who underwent treatment with recombinant human growth hormone (rhGH) at a dose of 0.035 mg/kg/day. The treatment resulted in a greater than 50% increase in height velocity from baseline over a 2-year period. No adverse effects were reported 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 developmental disorder associated with short stature, but limited data exist on the endocrine function and response to growth hormone therapy. Previous studies have shown variable responses to recombinant human growth hormone (rhGH) in children with short stature due to genetic conditions. This study aims to provide insights into the growth outcomes following rhGH therapy in a child with genetically confirmed ZTTK syndrome.
Methods
This is a case report involving a female child diagnosed with ZTTK syndrome. The child received rhGH at a dose of 0.035 mg/kg/day. The primary outcome measure was height velocity, assessed over a 2-year period.
Results
The treatment resulted in a greater than 50% increase in height velocity from baseline, improving from 4.3 cm/year to 7.2 cm/year. The height standard deviation score improved from -4.16 to -3.40. Insulin-like growth factor 1, thyroid function, glucose, and glycated hemoglobin A1c remained normal throughout the treatment.
Interpretation
The findings suggest a clinically significant growth response to rhGH in this case, despite the absence of biochemical GH deficiency. However, the single case design and lack of a control group limit the ability to generalize these results. Further studies are needed to confirm the efficacy of rhGH in similar populations and to assess long-term outcomes.
Key findings
- Insulin-like growth factor 1 (IGF-1) of 91 ng/mL, normal range 33.6-170.5 ng/mL.
- Peak growth hormone (GH) concentration of 7.2 ng/mL, above the cutoff for GH deficiency 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.
- No adverse effects were observed.
Limitations
- Single case report limits generalizability.
- No long-term follow-up data provided.
- No control group for comparison.