Sixtythree patients were treated surgically and 27 were treated medically. Diagnostic and treatment approach in cases of hyperinsulinism. Ordinarily, beta cells secrete just enough insulin to keep the blood sugar in the normal range. Few cases of persistent hyperinsulinemic hypoglycemia of infancy phhi have been reported, so far. Persistent hyperinsulinemic hypoglycemia of infancy, or phhi, is the most common cause of severe neonatal hypoglycemia that lasts beyond the first a few hours of life. Pmm2cdg and mpicdg congenital disorder of glycosylation ia and ib and the beckwithwiedemann, perlman, insulin resistance, sotos, timothy, ondine and usher. Persistent hyperinsulinemic hypogylcemia in infants. These conditions are present at birth and most become apparent in early infancy. Pdf persistent hyperinsulinemic hypoglycemia of infancy. Successful therapy with calcium channel blocker nifedipine in persistent neonatal hyperinsulinemic hypoglycemia of infancy. It was first identified in 1938, when laidlaw coined the term nesidioblastosis to describe the neodifferentiation of islets of langerhans from pancreatic ductal epithelium a term since replaced by phhi and chi.
Because of the high levels of insulin, people with this disease have frequent episodes of low blood sugar hypoglycemia that can even occur after eating. Transient neonatal hypoglycemia 1st 24 hours of life. Request pdf persistent hyperinsulinemic hypoglycemia of infancy phhi. Looking for online definition of persistent hyperinsulinaemic hypoglycaemia of infancy in the medical dictionary. Persistent hyperinsulinemic hypoglycemia of infancy, journal. Congenital hyperinsulinism hi is the most frequent cause of severe, persistent hypoglycemia in newborn babies, infants, and children. Unless early and aggressive intervention is undertaken, brain damage from. Congenital hyperinsulinism chi is the most frequent cause of severe persistent hypoglycemia in early infancy.
We report a case of chi with diffuse pancreatic abnormality diagnosed preoperatively using the 68 ga octreotide dota noc positron emission tomography scan. The incidence is estimated at 150,000 live births, but it may be as high as 12,500 in countries where consanguinity is common. To report a case of persistent hyperinsulinemic hypoglycemia in twins which is a situation not yet reported in the literature. Treatment that prevents the occurrence of these sequele is essential. Congenital hyperinsulinism hi is a genetic disorder in which the insulin cells of the pancreas, called beta cells, secrete too much insulin. An infant with persistent hyperinsulinemic hypoglycemia received diazoxide and developed pulmonary hypertension, heart failure, and neutropenia 119 a a girl with macrosomia, who was delivered by cesarean section at 34 weeks, developed seizures and hypoglycemia in the first days of life due to hyperinsulinemia and was given octreotide and diazoxide. Diagnosis and management of hyperinsulinaemic hypoglycaemia. Hypoglycemia in infants and children can lead to seizures, developmental delay, and permanent brain damage. Although the disease is rare in outbred communities approximately 1 case per 50,0. Hyperinsulinemic hypoglycemia, familial, 1 concept id. Familial persistent hyperinsulinemic hypoglycemia of infancy. Homozygosity mapping, to chromosome 11p, of the gene for. Neurologic outcomes of 90 neonates and infants with. Therapy for persistent hyperinsulinemic hypoglycemia of.
Although an excellent argument for the designation phhi has been made, the term nesidioblastosis is more commonly used. Recent discoveries in the molecular and biochemical regulation of insulin secretion h. Congenital forms of hyperinsulinemic hypoglycemia can be transient or persistent, mild or severe. The inappropriate oversecretion of insulin is responsible for profound hypoglycemias, which require aggressive treatment to prevent severe and irreversible brain damage.
It usually presents with seizures, hypotonia, poor feeding, apnea, and coma in the neonatal period or infancy, along with high birth weight. Persistent hypoglycemia and hyperinsulinemia neonatology. It is a disorder of glucose homeostasis characterized by. Congenital hyperinsulinism is a disease where there are abnormally high levels of insulin, a hormone produced by the beta cells of the pancrea s that helps control blood sugar levels. Hi is characterized by dysregulated insulin secretion, which results in persistent mild to severe hypoglycemia.
Manifestations of hyperinsulinemic hypoglycemia vary by age and severity of the hypoglycemia. Hyperinsulinism hi is the most common cause of both transient and permanent disorders of hypoglycemia. The neurologic development of 90 phhi patients was studied retrospectively. In the past, before the different genetic forms of hi were recognized, hi was referred to by many names, including nesidioblastosis, islet cell dysregulation syndrome, idiopathic hypoglycemia of infancy, and persistent hyperinsulinemic hypoglycemia of infancy. Hyperinsulinemia or persistent hyperinsulinemia hypoglycemia of infancy phhiidmcongenital hyperinsulinemia congenital hypopituitarism. Hyperinsulinismhyperammonemia syndrome hiha is the second most common form of persistent hyperinsulinemic hypoglycemia of infancy. Hi has subsequently been referred to by many names, including leucinesensitive hypoglycemia, islet dysregulation syndrome, persistent hyperinsulinemic hypoglycemia of infancy, and nesidioblastosis. About 60% of babies with hi are diagnosed during the first month of life. Neartotal pancreatectomy for persistent hyperinsulinemic.
Nov 01, 2000 after completing this article, readers should be able to. Inappropriately elevated insulin secretion is the hallmark of persistent hyperinsulinemic hypoglycemia of infancy phhi, also denoted congenital hyperinsulinism. Persistent hyperinsulinemic hypoglycemia of infancy phhi is relatively rare but one of the most important. Persistent hyperinsulinemic hypoglycemia of infancy phhi.
Persistent hyperinsulinemic hypoglycemia of infancy, also known as congenital hyperinsulinism, is one of the causes of refractory and persistent hypoglycemia4. Congenital hyperinsulinism is a medical term referring to a variety of congenital disorders in which hypoglycemia is caused by excessive insulin secretion. The mechanism of transient hyperinsulinemic hypoglycemia is unclear, as opposed to persistent hyperinsulinemic hypoglycemia of infancy that is associated with genetic defects in atpsensitive potassium katp channels composed mainly of kir6. Persistent hyperinsulinemic hypoglycemia of infancy phhi is a disorder of childhood associated with inappropriate hypersecretion of insulin by the pancreas. An external file that holds a picture, illustration, etc. Understanding the responsiveness of beta cells to diazoxide and somatostatin. Persistent hyperinsulinemic hypoglycemia of infancy phhi, also known as familial hyperinsulinism and nesidioblastosis, is a disorder of glucose homeostasis. Persistent hyperinsulinemic hypoglycemia springerlink. We examined the mtor pathway and cell cycle data in the exocrine pancreas in diffuse persistent hyperinsulinemic hypoglycemia of infancy phhi. For decades, the disease has been ascribed to nesidioblastosis.
Although rare, this disorder is the most common cause of persistent hyperinsulinemia in children. Persistent hyperinsulinemic hypoglycemia of infancy, american. Recent studies have demonstrated a role for calcium channel blocking agents in the treatment of persistent hyperinsulinemic hypoglycemia of infancy. Neonatal insulin secretion and persistent hyperinsulinemia of. It is persistent hyperinsulinemic hypoglycemia of infancy. Diabetes mellitus type 2maturityonset diabetes of the young, type 2permanent neonatal diabetes mellitushyperinsulinemic hypoglycemia familial 3from uniprot. Backgroundpurpose persistent hyperinsulinemic hypoglycemia of infancy phhi is the most common cause of persistent hypoglycemia in infancy with consequences such as seizures and brain damage. In addition, one hyperinsulinemic infant was recently found. Familial persistent hyperinsulinemic hypoglycemia of infancy and. Hyperinsulinemic hypoglycemia is defined as inappropriately elevated plasma insulin concentration in the presence of hypoglycemia persistent hyperinsulinemic hypoglycemia of infancy phhi, an autosomal recessive disorder characterized by unregulated insulin secretion, is linked to chromosome 11p1415. Hyperinsulinemic hypoglycemia hh is one of the most common causes of persistent hypoglycemic episodes in neonates.
Most common cause of persistent hypoglycemia in infancy. Persistent hyperinsulinemic hypoglycemia of infancy how. Congenital hyperinsulinism affecting the whole of the pancreas, in contrast to focal congenital hyperinsulinism where an isolated part of the pancreas is affected. Jan 01, 2003 in persistent hyperinsulinemic hypoglycemia phhi of infancy, secretion of insulin is unregulated, resulting in profound hypoglycemia. Persistent hyperinsulinemic hypoglycemia of infancy cohen. Persistent hyperinsulinemic hypoglycemia of infancy phhi is the most important cause of hypoglycemia in early infancy. Familial hyperinsulinism, also referred to as congenital hyperinsulinism, nesidioblastosis, or persistent hyperinsulinemic hypoglycemia of infancy pphi, is the most common cause of persistent hypoglycemia in infancy and is due to defective negative feedback regulation of insulin secretion by low glucose levels. The main concern in the management of phhi is to prevent severe hypoglycemia. Any infant with persistent or recurrent hypoglycemia should be screened for hyperinsulinism.
Hh can be either transient or persistent congenital hyperinsulinism. Phhi is caused by mutations in sur1, which is a member of the atp. Persistent hyperinsulinemic hypoglycemia of infancy is caused by inappropriate and excessive secretion of insulin. The focal form of persistent hyperinsulinemic hypoglycemia. Therapy for persistent hyperinsulinemic hypoglycemia of infancy. Congenital hyperinsulinism chi is the most common cause of persistent hypoglycemia in neonates and infants. An overview of current concepts department of pediatric surgery, lady hardinge medical college and associated kalawati saran childrens hospital, new delhi, india department of pediatric surgery, lady hardinge medical college and associated kalawati saran childrens hospital, new delhi, india. Jun 01, 2012 abstract congenital hyperinsulinism chi is the most frequent cause of severe, persistent hypoglycemia in infancy and childhood. Mild cases can be treated by frequent feedings, more severe. The first one, diffuse phhi, is mostly related to mutations in the genes coding for the sulfonylurea receptor abcc8, formerly sur1. Sep 11, 2003 in persistent hyperinsulinemic hypoglycemia phhi of infancy, secretion of insulin is unregulated, resulting in profound hypoglycemia.
Current pharmacologic treatment of neonatal hh includes diazoxide and octreotide, whereas for diffuse, unresponsive cases a subtotal pancreatectomy may be the last resort, with questionable efficacy. Persistent hyperinsulinaemic hypoglycaemia of infancy. Persistent hyperinsulinemic hypoglycemia of infancy phhi, also referred to as congenital hyperinsulinism, familial hyperinsulinemic hypoglycemia, and primary islet cell hypertrophy nesidioblastosis, is the most common cause of persistent hypoglycemia in neonates and infants. Congenital hyperinsulinism nord national organization for. Tissues from two diffuse phhi cases, one pediatric control and from adult pancreatic tissue microarray were analyzed.
Familial persistent hyperinsulinemic hypoglycemia of infancy phhi, an autosomal recessive disorder characterized by unregulated insulin secretion, is linked to chromosome 11p1415. Hi was first described in 1954 by macquarrie as idiopathic hypoglycemia of infancy. Longterm outcome following 95% pancreatectomy objective. Permanent neonatal diabetes and hyperinsulinemia of infancy. Hyperinsulinemic hypoglycemia an overview sciencedirect. Kane c, lindley kj, johnson pr, james rf, milla pj, aynsleygreen a, dunne mj. The disorder is characterized by inappropriate insulin secretion in the face of hypoglycemia, and is diagnosed by demonstrating hypoketotic hypofatty acidemic hypoglycemia in association with hyperinsulinism and an elevated glucose requirement. When medical therapy fails or complications are anticipated, early pancreatectomy is recommended to maintain euglycemia. Genetic mutations are identified in 50% of these patients whereas in the remaining 50%, no.
Pdf a case of persistent hyperinsulinemic hypoglycemia of infancy. Hyperinsulinismhyperammonemia syndrome in an infant with. A neonate with resistant and prolonged hypoglycemia. Philadelphia congenital hyperinsulinism center, was held in philadel. To evaluate the neurologic outcomes of neonates and infants suffering from persistent hyperinsulinemic hypoglycemia of infancy phhi. Infant welfare movement iwm began in 1870 in europe to decrease infant mortality. Hyperinsulinemic hypoglycemia can be transient, prolonged or persistent congenital. In babies and young children, these episodes are characterized by a lack of energy lethargy, irritability, or difficulty feeding. Encyclopedia of endocrine diseases second edition, 2019.
Brain injury due to persistent hyperinsulinemic hypoglycemia. Congenital hyperinsulinism is a condition that causes individuals to have abnormally high levels of insulin, which is a hormone that helps control blood sugar levels. Persistent hyperinsulinemic hypoglycemia of infancy listed as phhi. Nov 01, 2002 in infants and children, as in adults, the most common cause of persistent hypoglycemia is hyperinsulinism. Congenital hyperinsulinism genetic and rare diseases. Persistent hyperinsulinemic hypoglycemia of infancy an. It is also referred to as congenital hyperinsulinism chi, familial hyperinsulinemic hypoglycemia, and primary islet cell hypertrophy nesidioblastosis. Loss of functional katp channels in pancreatic betacells. Hypoglycemia can be detrimental to the developing central nervous system, resulting in longterm effects. Here we report a case of congenital diffuse neonatal hh, first suspected when.
Genetic analysis revealed homozygous abcc8 splicing mutation. In most countries it occurs in approximately 125,000 to 150,000 births. A combination of nifedipine and octreotide treatment in an hyperinsulinemic hypoglycemic infant. Diazoxide treatment for persistent hypoglycemia in a small. A 71yearold chinese woman with autoimmune hashimotos hypothyroidism and mixed connective tissue disease mctd was referred to the endocrine unit for frequent episodes of hypoglycemia. List the genes responsible for katp channel activity. Two different histological forms of persistent hyperinsulinemic hypoglycemia of infancy phhi have been recognized 14 with distinct therapeutic implications. Hypoglycemia due to hyperinsulinemia is the most common cause of persistent hypoglycemia in infants and children.
Describe the major characteristics of the form of disease associated with loss of katp channel function. Severe persistent hyperinsulinemic hypoglycemia due to a. We used the homozygosity genemapping strategy to localize this disorder to the region of chromosome 11p between markers d11s34 and d11s899 maximum lod score 5. Practical management of hyperinsulinism in infancy adc. Congenital hyperinsulinism chi persistent hyperinsulinemic hypoglycemia of infancy octreotide and sandostatin only authorization of 6 months may be granted for treatment of chi and persistent hyperinsulinemic hypoglycemia in an infant.
We show here that insulinsecreting cells from a homogeneous group of. There is no clear definition of the precise duration of transient hypoglycemia. What is persistent hyperinsulinaemic hypoglycaemia of infancy. Apr 01, 2021 persistent hyperinsulinemic hypoglycemia of infancy phhi is the most common cause of recurrent hypoglycemia in neonates and infants. Report of seizures in identical twins, from consanguineous parents, with persistent hypoglycemia as cause of the seizures. A baby girl presented with hypoglycemic seizures since the first postnatal day as well as with inappropriate hyperinsulinemia. The focal form of persistent hyperinsulinemic hypoglycemia of. Brain injury due to persistent hyperinsulinemic hypoglycemia of infancy. Congenital hyperinsulinism is a disease where there are abnormally high levels of insulin, a hormone produced by the beta cells of the pancreas that helps control blood sugar levels. Persistent hyperinsulinemic hypoglycemia of infancy springerlink. Neonatal hypoglycemia can be transient see chapter 75 on transient hypoglycemia or persistent hyperinsulinism, hypopituitaryism, disorders of gluconeogenesis, glycogenolysis, fatty acid oxidation, or inborn errors of metabolism. This hypoglycemia can be transient, which, in the majority of infants, will be asymptomatic and. Pdf introduction persistent hyperinsulinemic hypoglycemia of infancy phhi is relatively rare but one of the most important causes of severe.
Persistent hyperinsulinemic hypoglycemia of infancy mainly occurred in infants. The fourth edition of the diagnostic statistical manual of mental d. This term, first coined by laidlaw, describes the persistence of a. We report a 30 day old infant with phhi whom we successfully treated with oral nifedipine alone. Persistent hyperinsulinemic hypoglycemia of infancy phhi is the most common cause of severe, prolonged neonatal hypoglycemia, occurring in 1 in 50,000 births.
Familial hyperinsulinemic hypoglycemia caused by a defect in. Neurologic outcomes of 90 neonates and infants with persistent. Advances in diagnosis and treatment of hyperinsulinism in. Causal mutations have been uncovered in genes coding for the. Apr 02, 2018 persistent hyperinsulinemic hypoglycemia of infancy. Persistent hi a number of different genetic defects causing hi have been identified. Neonatal ward files were evaluated to validate hypoglycemia diagnoses. Identify the primary classifications of persistent hyperinsulinemia of infancy. Persistent hyperinsulinemic hypoglycemia of infancy phhi is the most common cause of persistent hypoglycemia in neonates and infants. Chi is characterized by unregulated insulin secretion from pancreatic. Transient hyperinsulinemic hypoglycemia this is observed often in idm, sga infants and in infants who had perinatal asphyxia, polycythemia and rh isoimmunization.
Total or subtotal pancreatectomy is normally required for the infants, despite the. Pulmonary hypertension occurring with diazoxide use in a. The pathogenesis of the condition has hitherto remained controversial. Familial persistent hyperinsulinemic hypoglycemia of infancy phhi is a rare, autosomal recessive disease of unregulated insulin secretion, defined by elevations in serum insulin despite severe hypoglycemia. Persistent hyperinsulinemic hypoglycemia of infancy. In the absence of treatment, hi can result in permanent brain damage 1, 2. Original article persistent hyperinsulinemic hypoglycemia of infancy. Hyperinsulinism is the most common cause of persistent or recurrent hypoglycaemia in infancy.
Congenital isolated hyperinsulinism chi, a rare endocrine disease is the most frequent cause of severe and. Meaning of persistent hyperinsulinaemic hypoglycaemia of infancy medical term. Excess insulin causes low plasma sugar hypoglycemia or low blood sugar. Delineate the clinical findings associated with persistent hyperinsulinemia of infancy. Differential diagnosis includes transient hyperinsulinemic hypoglycemia in newborns of mothers with diabetes mellitus or after perinatal stress.
The incidence is estimated at 150,000 live births, but it may be as high as. A few miscellaneous symptoms are harder to attribute to either of these. Congenital hyperinsulinism nord national organization. Explore symptoms, inheritance, genetics of this condition.
891 566 306 1353 597 379 758 1216 808 115 1190 63 721 782 1509 78 1286 584 1177 1252 355 1155 245 1301 604 179 1402 1353 649 244 509 501 1212 11 1