Hypoglycemia - How it Relates to Kabuki Syndrome
Hypoglycemiai, or the presence of low blood sugar, usually measured as glucose, is most often reported as a short-lived problem in newborns with Kabuki syndrome. Glucose is the primary fuel source for the brain. If the glucose levels remain low, below an accepted “safe” level of about 60 mg/dl, it may expose a child to the risk of brain injury. Some individuals with Kabuki syndrome, however have persistent hypoglycemia throughout infancy and childhood. The underlying cause has not been found in most cases—most likely because it has not been studied well and reported in the medical literature. There are case reports suggesting some may release too much insulin—a hormone made in the pancreas that helps to lower and regulate blood sugar levels. There have also been cases reported of other hormone deficiencies that to some degree regulate blood sugar levels. These include growth hormone, adrenocorticotropic hormone (ACTH) and cortisol. There may also be other undescribed biochemical or metabolic reasons for some children with Kabuki syndrome to have hypoglycemia.
The behavioral symptoms of hypoglycemia, which overlap with nonspecific normal behaviors, can be easily overlooked. Most children experience some of the following symptoms. Infants with low blood glucose may have, low tone or floppiness (hypotonia), poor feeding, seizures, and pauses in breathing (apneai). In older children, symptoms may include sudden irritability, hunger, nervousness, shakiness, perspiration, dizziness, light-headedness, sleepiness, confusion, difficulty speaking, or feeling anxious or weak. Suggestions that low blood sugar may occur at night, while sleeping, include crying out or having nightmares, or finding pajamas or sheets that are damp from sweating. Children may be tired, irritable, or confused when they wake up. As you can see, these symptoms are common childhood behaviors, so there is some intuition required to feel that your child “just isn’t right” and request that your physician begin to explore if low blood sugar is a possible cause. A simple test parents can do to confirm their suspicions is to see if the symptom is relieved by providing a source of simple sugars, such as a half cup of fruit juice, sugar candies (~eight lifesavers), a quarter cup of raisins, etc. The symptoms should resolve within ten to twenty minutes after eating if it is due to low blood glucose.
What is done for hypoglycemia? In most cases, a pediatric endocrinologist should help with diagnosis and management. First—how often does it occur? The amount of time that the patient’s blood sugar is low is determined—often while a child is hospitalized, but it may be initiated with home blood glucose testing. At home, blood sugar may be monitored with a blood glucose meter identical to the device that an individual with diabetes mellitus would use. Treatment is tailored to the severity of hypoglycemia and its cause. Specific recommendations are impossible to recommend at this time, because no one common cause has been found for hypoglycemia in Kabuki syndrome. Minimally, simultaneous measurement of blood glucose and insulin levels should be performed. Usually, if a person has low blood glucose, insulin secretion is suppressed and measures very low. Measurement of the amount of glucose needed to keep blood sugars in the normal range should be done (determined by milligrams of glucose needed per kilogram of patient per minute). Additional testing to assist in the diagnosis of a cause of hypoglycemia may include measuring free fatty acids, lactic acid and ketone bodies in the blood as well as ketone bodies in the urine during an episode of hypoglycemia. Beyond these tests, evaluation and interpretation of results becomes much more complex, with measurement of other hormones, organic acids or acylcarnitines. A glucagon stimulation test may be necessary. For unusual cases, the best evaluation is probably achieved by an endocrinologist working in conjunction with a biochemical genetics specialist.
Treatment is directed at making sure sufficient food is provided to prevent low blood glucose. Frequent feedings and avoidance of prolonged fasting may be necessary, but some individuals have required continuous drip feeds through a feeding tube or modified formulas and supplements. Stressful situations, such as illnesses, even minor viral infections, may make management of hypoglycemia difficult. In the case of prolonged inability to take food or to keep food down because of vomiting, other methods of maintaining blood sugar levels are necessary. An intravenous (IV) line, placed in a vein, can be provide glucose with IV fluid. The amount of glucose and rate of fluid provided will need to be individualized for each patient depending on the assessment of their clinical condition.
There are few reports of treatment of hypoglycemia in patients with Kabuki syndrome beyond the need for frequent feedings. Perhaps some have been treated with medications that are used for some other causes of hypoglycemia, such as producing too much insulin. One such drug, Diazoxide (trade name Hyperstat or Proglycem in the USA), may be used in combination with other drugs to keep the blood sugar in a safe range. Clearly, further reports of management of hypoglycemia in Kabuki syndrome are needed. Since it is a rare complication of a not-so-rare genetic syndrome, no one physician will have much experience. The Kabuki Syndrome Network can serve as a clearinghouse to connect family and physicians so that there is increased awareness of the potential for hypoglycemia.
I would be interested to hear about the experience of families, because this is clearly an area of management that requires more study.
About Author: Dr. Mark C. Hannibal is a clinical geneticist and immunologist at the University of Washington School of Medicine. He has a research interest in Kabuki syndrome. Along with Dr. Hiroshi Kawame, Dr. Bonnie Pagon and Dr. Louanne Hudgins, he published a case series of Kabuki syndrome patients in the Journal of Pediatrics. Dr. Hannibal now follows many patients from Washington state, Idaho and Alaska.