Novel Hypoglycemia Phenotype in Congenital Hyperinsulinism Due to Dominant Mutations of Uncoupling Protein 2.

Context: The rarest genetic form of congenital hyperinsulinism (HI) has been associated with dominant inactivating mutations in uncoupling protein 2 (UCP2), a mitochondrial inner membrane carrier that modulates oxidation of glucose vs amino acids.

Objective: To evaluate the frequency of UCP2 mutations in children with HI and phenotypic features of this form of HI.

Design: We examined 211 children with diazoxide-responsive HI seen at The Children's Hospital of Philadelphia (CHOP) between 1997 and October 2016.

Neonatal diabetes: current trends in diagnosis and management.

The purpose of this article is to describe diabetes diagnosed during the first 6 months of life. Neonatal diabetes, also known as congenital diabetes, presents a unique set of challenges for the pediatric healthcare provider. Neonatal diabetes is not type 1 diabetes.

Pregnancy in glycogen storage disease type Ib: gestational care and report of first successful deliveries.

Patients with type Ia glycogen storage disease (GSD) have been surviving well into adulthood since continuous glucose therapy was introduced in the 1970s, and there have been many documented successful pregnancies in women with this condition. Historically, few individuals with type Ib GSD, however, survived into adulthood prior to the introduction of granulocyte colony stimulating factor (G-CSF) in the late 1980s. There are no previously published reports of pregnancies in GSD type Ib.

Clinical features and insulin regulation in infants with a syndrome of prolonged neonatal hyperinsulinism.

Objectives: To characterize the clinical features and insulin regulation in infants with hypoglycemia due to prolonged neonatal hyperinsulinism.

Study Design: Data were collected on 26 infants with hypoglycemia due to neonatal hyperinsulinism that later resolved. Acute insulin response (AIR) tests to calcium, leucine, glucose, and tolbutamide were performed in 11 neonates.

Effects of hypoglycemia on developmental outcome in children with congenital hyperinsulinism.

Children with congenital hyperinsulinism are at risk for recurring, severe episodes of hypoglycemia that can cause seizures, brain damage, and developmental delay. To assess the frequency of permanent brain damage in this disorder, we carried out a telephone survey of 68 children who presented to The Children's Hospital of Philadelphia between 1980 and 2000. One third of the group had some degree of developmental delay.

Central nervous system hyperexcitability associated with glutamate dehydrogenase gain of function mutations.

Objective: To describe seizure phenotypes associated with the hyperinsulinism/hyperammonemia syndrome (HI/HA), which is caused by gain of function mutations in the enzyme glutamate dehydrogenase (GDH).

Study Design: A retrospective review of records of 14 patients with HI/HA.

Results: Nine patients had seizures as the first symptom of HI/HA, and six had seizures in the absence of hypoglycemia.

Familial leucine-sensitive hypoglycemia of infancy due to a dominant mutation of the beta-cell sulfonylurea receptor.

Familial leucine-sensitive hypoglycemia of infancy was described in 1956 as a condition in which symptomatic hypoglycemia was provoked by protein meals or the amino acid, leucine. The purpose of this study was to determine the genetic basis for hypoglycemia in a family diagnosed with leucine-sensitive hypoglycemia in 1960. Recently diagnosed family members showed a dominantly transmitted pattern of diazoxide-responsive hyperinsulinism (HI).

Preoperative evaluation of infants with focal or diffuse congenital hyperinsulinism by intravenous acute insulin response tests and selective pancreatic arterial calcium stimulation.

Infants with congenital hyperinsulinism often require pancreatectomy. Recessive mutations of the ATP-dependent plasma membrane potassium channel (K(ATP)) genes, SUR1 and K(ir)6.2, cause diffuse hyperinsulinism.

Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor.

Recessive mutations of sulfonylurea receptor 1 (SUR1) and potassium inward rectifier 6.2 (Kir6.2), the two adjacent genes on chromosome 11p that comprise the beta-cell plasma membrane ATP-sensitive K(+) (K(ATP)) channels, are responsible for the most common form of congenital hyperinsulinism in children.