medwireNews: Recombinant human growth hormone (rhGH) appears to have a positive effect on growth in children with Kabuki Syndrome, shows an open-label study.
“The cause of the short stature in [Kabuki Syndrome] remains unclear”, say Dina Schott (Zuyderland Medical Centre, Heerlen, the Netherlands) and co-researchers.
Among 18 prepubertal children (nine boys and nine girls) with genetically confirmed Kabuki Syndrome in the team’s study, just four were GH deficient.
All were treated with a standard dose of rhGH (average of 0.96 mg/m2 per day) for 2 years, however, during which time their average height standard deviation score (SDS) improved from –2.40 at baseline to –1.30 at the end of treatment.
Thirteen (72%) children achieved at least an improvement in height SDS of 0.5 by the end of the first year of treatment, as did 16 (89%) by the end of the second.
The two nonresponders achieved height SDS improvements of 0.28 and 0.36. One had their rhGH dose reduced because of ongoing headaches during treatment, and the other was “somewhat older” than the cohort on average, being aged 9.5 years at baseline compared with approximately 6–7 years, and was growing normally prior to treatment.
The researchers note that younger age at baseline was associated with a larger gain in height SDS during treatment. Treatment response did not differ according to the underlying Kabuki Syndrome mutation, or whether the children had short stature or were within the normal range at baseline.
Only three patients, who had a guideline-compliant indication, continued rhGH after the 2-year study period. The 15 patients who stopped treatment had a decline in average height SDS from –1.32 to –1.60 over the following year.
Bone age was delayed by around 1 year at baseline, and increased from an average of 5.9 to 8.5 years during treatment, reducing the delay to about 6 months.
The researchers note that obesity is common in children with Kabuki Syndrome later in childhood, and that fat storage tends to be primarily abdominal.
“Therefore, we hypothesized that [Kabuki Syndrome] patients are predisposed to an elevated risk for developing metabolic syndrome in adulthood”, they write in Hormone Research in Paediatrics.
In this study cohort the average baseline BMI SDS was 0.56, which reduced to 0.18 during treatment but rose again to an average of 0.49 in the year after its cessation.
Four children were obese at baseline and experienced a borderline significant reduction in average BMI SDS during treatment, from 3.01 to 1.74. There was a significant reduction in waist-to-height ratio in the cohort overall, from 0.50 to 0.47, and a nonsignificant reduction in the subgroup with obesity, from 0.58 to 0.51.
“Despite the small study size, this indication is clinically important with regard to the prevention of truncal obesity and therefore the eventual risk on the development of the metabolic syndrome”, say Schott and team.
They also found that low-density lipoprotein (LDL) cholesterol levels decreased during rhGH treatment, along with levels of apolipoprotein B100, suggesting that “not only LDL cholesterol concentrations, but also the number of LDL particles was reduced.”
The researchers say: “This finding points to a preventative intervention against cardiovascular problems later in life”, adding that longer-term follow-up is needed to confirm this.
By Eleanor McDermid
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