The monitoring and treatment of children with IKH should be individualized according to severity, frequency and response. While physiological KH only will need attention in case of acute illness or prolonged fasting, pathological KH may need everyday monitoring and treatment. POC glucometers have different diagnostic performances and are less reliable in the lower range.
Moreover, finger-prick capillary PG concentrations derive from the optimal venous PG concentration, and the automatic 1.1 conversion factor from whole blood POC glucometers to report PG concentrations may not reflect the actual erythrocyte volume fraction of an infant. Despite these limitations, home monitoring with POC testing for PG and ketones should be used in monitoring KH in its severe forms. POCT for blood BOHB should be preferred from the less precise urine stix AcAc.
As the frequency and severity of KH episodes vary, the need for home monitoring must be individualized for each patient. Severely affected children may benefit from CGM, although low glucose values or decreasing trend alarms should be controlled with a glucometer to improve precision.. As hyperketonemia may be of clinical significance without simultaneous hypoglycemia, blood ketone monitoring may be recommended for normoglycemic patients exhibiting signs and symptoms of illness.
Point of Care
POC monitoring may be an economic burden on the family, as well as a logistical challenge for custodial daycare and school personnel. On the other hand, POC testing may facilitate the correct identification of episodic behavioral changes as symptoms of KH instead of general “bad behavior”, psychosocial reactions, or ADHD, which had occurred according to the anecdotal experience in the new patient organization, KHI. Still, the need of monitoring should be evaluated regularly to avoid both “over”- and “under”-monitoring.
The Pediatric Endocrine Society recommends maintaining a PG concentration of > 70 mg/dL (3.9 mmol/L) as goal of treatment for hypoglycemia in infants and children, however allowing for an individualized, tailored approach to management. To the authors´ experience, children with pathological KH benefit from an individualized PG goal to keep BOHB < 1.0 mmol/L. This may fit with a PG kept > 70 mg/dL (3.9 mmol/L), but an individual PG goal for each child to avoid hyperketosis should be determined in the diagnostic process.
Nutritional therapy, avoidance of prolonged fasting, increased frequency of feedings, and close monitoring of oral intake, especially in times of stress or high activity, are suggested to mitigate episodes of hypoglycemia. Uncooked cornstarch has been used to extend the times between feedings by delaying onset of hypoglycemia. Traditional cornstarch has been used for 40 years to prevent nocturnal hypoglycemia, with the measured length of time for digestion being 3–4 h.
For some children with pathological KH, as in those with KH due to GSD I, an overnight administration of cornstarch is necessary. In addition to cornstarch therapy, children with pathological KH that are unable to maintain fasting for any significant length of time may be evaluated for gastrostomy tubes for bolus or continuous tube feedings. Protein-rich diet or dietary products should be considered if low protein or prealbumin concentrations are documented. Proteins provide substrate for gluconeogenesis and may reduce muscle cramps associated to KH.
Nausea and vomiting caused by ketones may lead to further decline in PG if hyperketosis is not recognized and treated. The acute treatment principle includes administration of high glycemic index (i.e. dextrose-rich) foods or drinks to provide energy from glucose metabolism instead of fatty acid metabolism which leads to further ketone body formation.
If hypoglycemia is unable to be corrected or the child becomes increasingly unresponsive, emergency intervention should be sought. Buccal carbohydrate gel administration, intravenous (IV) dextrose or intramuscular glucagon (if proven effective and safe by formal testing) may be administered to raise PG concentrations to ≥ 70 mg/dL (3.9 mmol/L). Of note, some patients with IKH have a normal i.m. glucagon response without provoking lactate acidosis, unlike the response in those with GSD I.
Elimination of ketones can take hours, and if the child is in an acidotic state, IV fluid therapy may be needed to return the patient to homeostasis. Intravenous dextrose can help to stop ketogenesis and lipolysis, and rehydration assists in renal excretion of ketones. A better understanding of KH through identification of novel genetic causes may help physicians to target the treatment of children with pathological KH.
Source: Drachmann, D., Hoffmann, E., Carrigg, A. et al. Towards enhanced understanding of idiopathic ketotic hypoglycemia: a literature review and introduction of the patient organization, Ketotic Hypoglycemia International. Orphanet J Rare Dis 16, 173 (2021). https://doi.org/10.1186/s13023-021-01797-2