We appreciate the discussion by Hussain concerning our article on the administration of DL sodium β-hydroxybutyrate in two cases with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) as published in Pediatric Research (1).

The idea behind administration of DL sodium β-hydroxybutyrate was to provide an alternative energy fuel to protect the brain from damage potentially caused by recurrent hypoglycemic events. This is a neuroprotective approach, which is not expected to alter the natural history of hyperinsulinism. Therefore, with respect to insulin secretion and glucose homeostasis, preexisting treatment with octreotide and feeding schedules remained unchanged over the whole observational period.

The particular subject of this study was to show that oral DL sodium β-hydroxybutyrate accumulates in blood and crosses the blood brain barrier. The longer than necessary observation period allowed us to additionally evaluate possible side effects of DL sodium β-hydroxybutyrate. During the 5- to 7-month treatment period, octreotide demand and the frequency and degree of hypoglycemic episodes did not change. This strongly suggests that additional insulin secretion was not induced as a possible side effect of DL sodium β-hydroxybutyrate. Cardiocirculatory changes did not occur and preexisting ultrasonographic signs of hypertrophic cardiomyopathy even improved during the time course of observation in both patients. Cardiotoxicity as possible side effect of DL sodium β-hydroxybutyrate is thus unlikely. Vomiting or loss of “orality” was preexisting to the administration of DL sodium β-hydroxybutyrate and did not deteriorate upon treatment.

In our observational study, DL sodium β-hydroxybutyrate was administered as an ultima ratio in two infants with PHHI who suffered from recurrent hypoglycemic events despite extensive conventional treatment. Results are preliminary and further experimental and clinical studies are needed prior to general clinical application. In the light of the fact that short chain fatty acid oxidation defects such as SCAD and SCHAD deficiency may be associated with PHHI, we fully agree with Hussain et al. that patients who might potentially benefit from this treatment have to be selected carefully. Administration of DL sodium β-hydroxybutyrate in PHHI is complementary and is not a substitute of conventional therapy.