The Congenital Hyperinsulinism Center at Children’s Hospital of Philadelphia (CHOP) has seen more children with hyperinsulinism (HI) caused by Kabuki syndrome than any other pediatric hospital in the world: 33 children have been treated between 1998 and 2023.
With this many dual-diagnosed patients, the center was able to study data in their electronic medical records to identify features of HI in children with Kabuki syndrome that will help improve diagnosis and treatment of these patients going forward. The findings were published in the Journal of the Endocrine Society.
One Kabuki syndrome symptom: hypoglycemia
Kabuki syndrome (KS) is a genetic disorder that affects many body systems and can impact a child’s growth, intellect, facial features, skeleton, heart, gastrointestinal tract, immune system, hearing and glucose levels. It is estimated that 7% to 10% of babies with KS have low blood glucose levels, or hypoglycemia. For some children with KS and hypoglycemia, the cause of the hypoglycemia is HI. It is difficult to estimate how common HI is in children with Kabuki syndrome, because many babies with KS are not evaluated for hypoglycemia.
More than three-quarters of children seen at CHOP with HI associated with KS had hypoglycemia on the first day of life. However, for many children, it took much longer to diagnose the cause of the hypoglycemia as HI. An HI diagnosis was made at a median age of 1.8 months old for children in the study. However, the HI diagnosis for seven patients didn’t come until after their first birthday. Understanding the timing of HI diagnosis in children with KS is important. This is because recognizing hypoglycemia and making the correct diagnosis are key factors in reducing potential seizures and brain damage from low blood glucose levels.
The good news is that the front-line medication for HI, diazoxide, works well to control low blood glucose in most children with Kabuki syndrome; 92% of children in the study were able to control their HI with diazoxide. Some children with KS also have heart problems that can increase the risk of certain side effects of diazoxide, like fluid overload. At CHOP, pediatric cardiologists are consulted before starting diazoxide in children with heart problems, and all children treated with diazoxide are also given a diuretic. With this approach, children with KS treated with diazoxide were able to take this medication safely.
The children with KS who were not able to take diazoxide due to very severe heart problems, or who did not respond to diazoxide, were able to be managed with continuous dextrose solution through a gastrostomy tube.
50% of children ‘outgrew’ their HI
During the follow-up period, almost half of the children with HI associated with Kabuki syndrome were able to stop treatment for HI. The median age that treatment for HI was no longer needed was 2.8 years old. Some children with HI associated with KS required treatment much longer, beyond 10 years of age. How long HI lasts in children with KS can vary, so every child needs individualized treatment.
Some studies of children with HI associated with Kabuki syndrome have found that children with KS caused by variants in the KDM6A gene may be more likely to have HI than children with KS caused by variants in the KMT2D gene. However, this pattern was not found in the study of CHOP patients.
“This may be because HI is never diagnosed in some children with Kabuki syndrome, either because they are never tested for HI or they outgrow it before they are tested,” says Elizabeth Rosenfeld, MD, MSCE, CHOP and HI Center endocrinologist and lead author of the journal article.
The biggest takeaways from the study?
“First, all children with Kabuki syndrome should be screened for HI,” says Rosenfeld. “And the reverse is true: When we screen for HI, we should include the two most common KS genes, KMT2D and KDM6A, in the genetic testing. This is because some features of Kabuki syndrome may not be recognized in infants. This gives us to opportunity to make an earlier diagnosis and provide more complete care for children with Kabuki syndrome.”
Children with HI associated with KS are followed in Kabuki Syndrome Endocrinology Clinic at CHOP. CHOP also offers the Kabuki Syndrome Clinic, a multidisciplinary clinic with specialists from Genetics, GI, Nutrition and Immunology in addition to Endocrinology. Both clinics see patients who were diagnosed with Kabuki syndrome or who have had their KS care elsewhere.
You can read the full article, Clinical and Molecular Characterization of Hyperinsulinism in Kabuki Syndrome, here.
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The Congenital Hyperinsulinism Center at Children’s Hospital of Philadelphia (CHOP) has seen more children with hyperinsulinism (HI) caused by Kabuki syndrome than any other pediatric hospital in the world: 33 children have been treated between 1998 and 2023.
With this many dual-diagnosed patients, the center was able to study data in their electronic medical records to identify features of HI in children with Kabuki syndrome that will help improve diagnosis and treatment of these patients going forward. The findings were published in the Journal of the Endocrine Society.
One Kabuki syndrome symptom: hypoglycemia
Kabuki syndrome (KS) is a genetic disorder that affects many body systems and can impact a child’s growth, intellect, facial features, skeleton, heart, gastrointestinal tract, immune system, hearing and glucose levels. It is estimated that 7% to 10% of babies with KS have low blood glucose levels, or hypoglycemia. For some children with KS and hypoglycemia, the cause of the hypoglycemia is HI. It is difficult to estimate how common HI is in children with Kabuki syndrome, because many babies with KS are not evaluated for hypoglycemia.
More than three-quarters of children seen at CHOP with HI associated with KS had hypoglycemia on the first day of life. However, for many children, it took much longer to diagnose the cause of the hypoglycemia as HI. An HI diagnosis was made at a median age of 1.8 months old for children in the study. However, the HI diagnosis for seven patients didn’t come until after their first birthday. Understanding the timing of HI diagnosis in children with KS is important. This is because recognizing hypoglycemia and making the correct diagnosis are key factors in reducing potential seizures and brain damage from low blood glucose levels.
The good news is that the front-line medication for HI, diazoxide, works well to control low blood glucose in most children with Kabuki syndrome; 92% of children in the study were able to control their HI with diazoxide. Some children with KS also have heart problems that can increase the risk of certain side effects of diazoxide, like fluid overload. At CHOP, pediatric cardiologists are consulted before starting diazoxide in children with heart problems, and all children treated with diazoxide are also given a diuretic. With this approach, children with KS treated with diazoxide were able to take this medication safely.
The children with KS who were not able to take diazoxide due to very severe heart problems, or who did not respond to diazoxide, were able to be managed with continuous dextrose solution through a gastrostomy tube.
50% of children ‘outgrew’ their HI
During the follow-up period, almost half of the children with HI associated with Kabuki syndrome were able to stop treatment for HI. The median age that treatment for HI was no longer needed was 2.8 years old. Some children with HI associated with KS required treatment much longer, beyond 10 years of age. How long HI lasts in children with KS can vary, so every child needs individualized treatment.
Some studies of children with HI associated with Kabuki syndrome have found that children with KS caused by variants in the KDM6A gene may be more likely to have HI than children with KS caused by variants in the KMT2D gene. However, this pattern was not found in the study of CHOP patients.
“This may be because HI is never diagnosed in some children with Kabuki syndrome, either because they are never tested for HI or they outgrow it before they are tested,” says Elizabeth Rosenfeld, MD, MSCE, CHOP and HI Center endocrinologist and lead author of the journal article.
The biggest takeaways from the study?
“First, all children with Kabuki syndrome should be screened for HI,” says Rosenfeld. “And the reverse is true: When we screen for HI, we should include the two most common KS genes, KMT2D and KDM6A, in the genetic testing. This is because some features of Kabuki syndrome may not be recognized in infants. This gives us to opportunity to make an earlier diagnosis and provide more complete care for children with Kabuki syndrome.”
Children with HI associated with KS are followed in Kabuki Syndrome Endocrinology Clinic at CHOP. CHOP also offers the Kabuki Syndrome Clinic, a multidisciplinary clinic with specialists from Genetics, GI, Nutrition and Immunology in addition to Endocrinology. Both clinics see patients who were diagnosed with Kabuki syndrome or who have had their KS care elsewhere.
You can read the full article, Clinical and Molecular Characterization of Hyperinsulinism in Kabuki Syndrome, here.
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