Background: Methylmalonic acidemia (MMA) is an inborn error of metabolism affecting the catabolism of essential amino acids: valine, isoleucine, methionine, and threonine. A great problem in these children is that of a growth abnormality with progressive slowing of the statural growth rate, in contrast with a normal or even accelerated weight gain. These abnormalities are accompanied by bone demineralization and muscle hypotonia.
Objective and hypotheses: We propose conducting a prospective study to determine the metabolic effects and effects on growth of 2-year treatment with recombinant human GH (rhGH) in five children presenting with vitamin B12 non-responsive methylmalonic aciduria in the age group of 212 (prepubertal) age. Course will be assessed longitudinally with each patient acting as his/her own control. The primary goal of this study is that rhGH treatment, by increasing protein anabolism, enables an improvement in growth rate and a gain of at least 1 S.D. in 1 year. The secondary goal is that rhGH treatment improves metabolic equilibrium due to enhanced protein synthesis.
Method: The children will receive rhGH at a dose of 0.05 mg/kg per day as a single s.c. injection daily, 7 days a week. A glucagon test for GH should be performed since an important proportion of patients with organic acidurias suffer from partial or total GH deficiency. The analysis will be conducted after 1 year. If the treatment is shown to be effective, the children will be treated with rhGH for a further period of 1 year. An extension should be provided for patients with a favourable response.
Results: Proof of concept for therapy with rhGH in children with methylmalonic aciduria has already been achieved by several authors, the largest cohort has been treated in Paris where the primary end point unfortunately was not the stimulation of growth in these patients but rather focused on improvement of the metabolic parameters. One patient of ours has received rhGH according to the protocol described above and manifested improvement of growth of 2 cm during a period of 3 months.
Conclusion: Patients affected by MMA are prone to growth abnormalities. Therapy with rhGH of these patients is promising, but should be studied in a prospective manner in order to get guidelines in starting this adjuvant treatment in this particular patient population.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology