Date of admission :7 – 1- 2012

Date of discharge: 10 -4 -2012

Mother data : 32 years old G4 P2 Bocked with –ve screening No fever No PROM

History of baby delivered PT 33/52 with severe RDS

died at the age of 1 month due to sepsis

History of 1 sibiling (11 years old) having PHHI required near total pancreatectomy

Delivered cs due to prev 2cs Was bradycardiac Required +ve pressure

ventilation Apgar scor :5/1 & 9/5

Looks active pink not dysmorphic not cyanosed mildly distressed

v/s HR :140/m Tem :36.8 c RR :52 /M

Wt : 4.03 kg : HC :33 .5 cm Ht :52 cm

Ht CNS NAD Abd Chest : mild SC recession Gent : normal male genatalia

1-What is the chance of having PHHI ?2-When it will be presented ?3- How severe it will be ?4- chance of other possibilities ?5-Is there any role for PGD ?

RD settled quickly spontaneously . Admitted to NICU for blood glucose monitoring Initial Dx :1.2 mmol/l Started iv fluid D10 % at rate of 5.8 mg/kg/ min for the 1st 3 hrs is improving but slowly (1.2 – 1.8

- 2.8 -3.6 ) . But again swinging around 2.5 mmol/l

So glucose supply was increased After 8 hrs glucose reqirements reached

12.5 then 14.5 mg/kg /min so : Endocrinology consultation . Investigations for persistent hypoglycemia . Started on glucagon and octeriotide .

Glucagon infusion was increase to 1 mg /day .

Octeriotide was increased to 40 mcg/ kg /day .

Blood glucose is stable : so feeding started at the age of 1 week with slow increment.

The baby had 2 attacks of sepsis during his stay (E Coli , CONS) Managed by proper antibiotics

Once we have reached full feeding again blood glucose dropped

Feeding was decreased .

Glucagon + octeriotide was continued .

Plane for pancraeatectomy was put.

Blood glucose was stable on :

Glucagon infusion Octeriotide injection Feeding + PN 50/50

Patient was referred and accepted in KFSH where pancreatectomy was done

normal levels of blood glucose on oral octeriotide

Normal development

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI),

also referred to as :

congenital hyperinsulinism,

primary islet cell hypertrophy (nesidioblastosis),

Is the most common and most severe cause of persistent hypoglycemia in neonates and infants.

PHHI is a genetic disorder with both familial and sporadic forms,

characterized by dysregulation of insulin secretion.

The incidence of PHHI in individuals of northern European extraction is approximately 1:30,000 live births .

in genetically isolated populations with a high prevalence of consanguinity :

1:2675 in Saudi Arabia 1:3200 in central Finland .

normally When BG≺ 60 mg/dL (3.3 mmol/L) only small amounts of insulin are secreted.

In children who have PHHI, the normal relationship between plasma glucose concentration and insulin secretion is disturbed insulin is released even during periods of hypoglycemia.

This disturbance of the normal relationship between glucose concentration and insulin secretion can be caused by a variety of genetic mutations :

most commonly by mutations causing abnormal function or regulation of the ATP-dependent potassium (KATP) channel of the pancreatic beta cells

Many cases of PHHI arise in patients without a family history of the disease.

Nonetheless, a genetic basis can be identified in about 50 %of cases, attributable to defects in at least eight genes

ABCC8 gene (ATP-binding cassette, subfamily C, member 8), which encodes the SUR1 subunit of the KATP channel

KCNJ11 gene, which encodes the Kir6.2 subunit of the KATP channel

GLUD1 gene (glutamate dehydrogenase) GCK gene (glucokinase) HADH gene (3-hydroxyacyl CoA dehydrogenase

gene) HNF4A gene (hepatocyte nuclear factor 4-alpha) SLC16A1 gene (solute carrier family 16, member

1) UCP2 gene (uncoupling protein 2) 

Most cases of PHHI that have a defined molecular basis are AR and are caused by mutations in the genes encoding the KATP channel, which are located on chromosome 11p14 .

AD disease usually is caused by activating mutations in the GCK gene or regulatory mutations in GDH gene .

Identification of the genetic subtype of PHHI is helpful because this information can guide clinical management.

For example, patients with the most common genetic mutations (ABCC8 and KCNJ11 genes) are unlikely to respond to diazoxide treatment, as compared with those with GLUD1, HNF4A, and HADH mutations .

In PHHI, the histologic abnormalities in pancreatic structure are heterogeneous but can be grouped into 2 broad categories:

1. Focal adenomatous hyperplasia (found in ¼ - 1/3 of cases)

2. Diffuse abnormality of the islets

macrosomia (LGA) : seen in 1/3 of neonates with PHHI, particularly those with KATP channel or HNF4A mutations .

symptoms of hypoglycemia : poor feeding, lethargy, jitteriness, and

hypotonia) within the 1st few hours to days of life.

However, some are not diagnosed until later in the first year or during childhood .

Even within the same family, the severity of disease can vary substantially .

The presence of hepatomegaly suggests a metabolic disorder, such as

GSD, galactosemia, or fructosemia.

The presence of dysmorphic features suggests a different diagnosis.

Older children and adults may have signs of residual neurologic damage from episodes of prolonged hypoglycemia.

GSD Hypopituitarism Beckwith-Wiedemann Syndrome Metabolic

Blood Chemistry panel with bicarbonate Insulin, C-peptide Cortisol, growth hormone Free fatty acids, β-hydroxybutyrate, acetoacetate Lactate, ammonia Total and free cartinine

Urine Dip for ketones Organic acids

Ultrasonography, (CT) search for a focal mass in the pancreas. (MRI)

A newer imaging technique has been developed that uses positron emission tomography (PET) in conjunction with abdominal CT to distinguish between focal and diffuse disease and .

 This technique uses a novel isotope, fluorine-18 L-dihydroxyphenylalanine (18 F-L-DOPA), for which neuroendocrine cells have a high affinity.

TREATMENT GOALS The1ry goal of therapy in (PHHI) is the prevention

of : acute neurologic symptoms (eg, seizure,

lethargy, coma) and long-term sequelae (eg, epilepsy, mental

retardation, microcephaly) of prolonged and/or recurrent hypoglycemia .

Parenteral glucose usually is required to maintain the plasma glucose concentrations in a normal range (80 to 130 mg/dl or 4.4 to 7.0 mM).

high rates of glucose infusion (10 to 40 mg/kg per min) may be required to maintain euglycemia.

Iv glucagon (1 to 10 mcg/kg per hour, as a continuous infusion) may be helpful during the initial stabilization period and before surgery.

-Side effects: vomiting and rebound hypoglycemia

 is the 1st-line therapy.

It works by blocking the sulfonylurea receptors on the beta cells, resulting in opening of the KATP channels, and decreasing insulin release.

is administered in doses of 5 to 15 mg/kg per day divided into three doses.

side effects :hypertrichosis and sodium and water retention

can be tried as 2nd-line therapy to reduce insulin secretion if treatment with diazoxide is unsuccessful .

It is frequently started with the diazoxide in an attempt to obtain control of the plasma glucose concentration.

The dose  is 5 to 20 mcg/kg per day divided into 3 doses, but even higher doses have been used.

No clear maximum dose has been established for these children.

In some instances, 100 - 200 mcg/hour has been used for short periods of time to determine the potential for therapeutic efficacy.

Linear growth should be observed closely, as octreotide suppresses growth hormone secretion .

Cure :

If a solitary focal lesion can be identified and excised, the patient usually maintains blood glucose levels within the reference range without the need for medication or continuous feedings.

Hypoglycemia :

often persists even after a 95-98% pancreatectomy.

Hypoglycemia may be easier to control after partial pancreatectomy and may resolve months or years later or persist throughout life.

diabetes mellitus :

The risk appears to increase with the extent of pancreatic resection.

Patients who undergo partial pancreatectomy are at high risk for developing DM later in life.

DM is extremely rare after resection of focal lesions.

In some series, a high frequency of mental retardation, developmental delay, has been observed.

These findings are generally attributed to minimal brain damage from early hypoglycemic events,

regular follow-up visits with a pediatric endocrinologist to review :

blood glucose levels, - diet - growth medication side effects.

Home therapy must be individualized and usually involves 1 or more of the following:

Oral diazoxide, possibly in conjunction with oral chlorothiazide

Subcutaneous octreotide Subcutaneous glucagon (for emergency use)