NEONATAL METABOLIC DISORDERS

Neonatal metabolic disorders

Hypoglycemia Hyperglycemia Hypocalcemia Hypercalcemia Hypomagnesemia Inborn errors of metabolism

Hypoglycemia
Predisposing Conditions Intra uterine growth retardation Maternal diabetes mellitus Immaturity Erythroblastosis fetalis Miscellaneous factors severe birth asphyxia, hypothermia, septicemia and polycythemia

Large-for-dates infants Maternal therapy with beta blockers hypoglycemia would be provoked by milk feeding in leucine sensitivity, galactosemia, fructosemia

Situations where routine monitoring of blood glucose is recommended

Small-for-dates babies and smaller of the discordant twins Infants of diabetic mothers Preterm infants < 35 weeks gestation. Rhesus hemolytic disease of the newborn Babies with prolonged hypoxia, hypothermia, polycythemia, septicemia, cardiac failure

 Infants born to mothers receiving therapy with terbutaline, propranolol and oral hypoglycemic agent. Infants on IV fluids or total parenteral nutrition. Babies with symptoms suggestive of hypoglycemia

Clinical manifestations
Irritability of theCNS : jitteriness, coarse tremor, twitching Refusal of feeds Apathy Coma Episodes of apnea with cyanosis Tachypnea with irregular breathing Episodes of sudden pallor, limpness and hypothermia

Diagnosis
Asymptomatic hyperglycemia blood glucose level is below 40 mg/dl on two occasions in a baby without any clinical symptoms of hypoglycemia.

symptomatic hypoglycemia
on the basis of Whipples triad;

Presence of symptoms attributable to

hypoglycemia,

low true blood glucose documented by an

accurate and sensitive laboratory method and

disappearance of clinical symptoms when blood

glucose level is normalized

MANAGEMENT
Symptomatic cases. The baby should be kept warm In a symptomatic infant with seizures, give 5-10 ml/kg of 10% dextrose intravenously as a bolus. In the absence of seizures, symptomatic infant is given a mini-bolus of 2 ml/kg of 10% dextrose Blood glucose is monitored every 2 hours

 Hyperglycemia should be avoided as it is also known to cause brain damage The infant is completely weaned off intravenous infusion when his blood glucose values are stable at an infusion rate of 4 mg/kg/minute.

Asymptomatic cases.

Bolus administration of glucose is not

recommended in asymptomatic babies.

sugar-fortified feeds expectantly for the first

4 hours or so.

HYPERGLYCEMIA
plasma glucose value is more than 145 mg/dl. may occur following intravenous glucose infusion, exchange transfusion with citrate phosphate dextrose (CPD) blood and in anencephalic baby due to poor utilization of glucose.

HYPOCALCEMIA
Causes Early-onset hypocalcemia (First 3 days) Immaturity. Maternal diabetes mellitus. Complications during delivery. Late-onset hypocalcemia (classical neonatal tetany) It is characterized by onset of tetany at the age of 5 to 10 days in healthy term babies receiving artificial feeding

Clinical features
shallow rapid breathing with transient episodes of apneic attacks and cyanosis. Exaggerated neuromuscular activity Twitchings Some babies may show sustained ankle clonus

Diagnosis
Electrocardiogram Elevated serum phosphate Echocardiography

Management
Asymptomatic babies Give 2 ml/kg/dose of 10 percent calcium gluconate intravenously after dilution with equal volume of 5% dextrose every 6 hourly and continue for 48 hours Symptomatic babies gluconate 10 percent solution diluted with equal volume

of 5% dextrose should be injected slowly at a rate of less ban

1.0 ml per minute through an established intravenous line with continuous monitoring of heart.

 If hypocalcemia is unresponsive to calcium therapy, magnesium sulfate (0.2 ml per kg of 50 percent solution intramuscular in 2 doses 12 hours apart) should be administered This should be followed by maintenance oral dose of 0.2 ml/kg of 50% magnesium sulfate once daily for 3 days.

OSTEOPENIA OF PREMATURITY
The principal cause of osteopenia or metabolic

bone disease of prematurity is reduced stores of

calcium and phosphorus due to preterm birth.

Feeding with unfortified human milk or

parenteral nutrition without adequate

supplements of calcium and phosphorous

Administration of certain drugs

Clinical features
There is hypotonia and decreased linear growth. The softening of chest bones prominence of forehead, dolichocephaly, wide anterior fontanel, widened cranial sutures widening of wrists, knees and ankles with rachitic rosary Pathologic fractures

Prevention
daily oral supplements of calcium 160 mg/kg, phosphorus 80 mg/kg and vitamin 400 i.u. till they achieve a post conceptional maturity f 38 weeks administration of ostocalcium syrup (7.5-10.0 ml/kg/d) r tablet (1.0-1.5 tablet/kg/d) given in divided doses mixed with EBM three times a day

HYPERCALCEMIA
The common causes include; primary hyperparathyroidism, congenital transitory hyperparathyroidism in association with maternal hypoparathyroidism, congenital hypophosphatasia, subcutaneous fat necrosis, h ypervitaminosis A and D and use of thiazide diuretics. , low phosphate intake in preterm infants fed with unsupplemented human milk

clinical features
craniotabes,

poor feeding,
hypotonia, vomiting, polyuria, constipation,

fractures (hyperparathyroidism),
hypertension and nephrocalcinosis

Management
volume expansion with normal saline and furosemide (1 mg/kg iv q 8 hr.). Oral or parenteral phosphates (3.0-5.0 mg/ dl) Cortisone (10 mg/kg/d) or methyl prednisolone (2 mg/kg/d) is effective to correct hypercalcemia due to hypervitaminosis A and D Parathyroidectomy

HYPOMAGNESEMIA
metabolic defect may occur in association with hypocalcemia Hypomagnesemia should be suspected if

hypocalcemia is unresponsive to calcium

therapy.

The condition can be treated by administration

of 0.2 ml per kg of 50 percent magnesium sulfate solution

INBORN ERRORS OF METABOLISM

The overall incidence of IEMs is around 1:1350. Around 30 percent of inborn errors of metabolism are associated with involvement of central nervous system

The presence of an inborn error of metabolism should be suspected in the following situations
Previous history of unexplained neonatal deaths, unexplained seizures and mental retardation or of a known metabolic disorder Unexplained cerebral depression with refusal of feeds The abnormal smell either from the baby or
his urine and presence of ketonuria

 Unexplained vomiting and/or diarrhea,

dehydration

Failure to thrive
Facial dysmorphism and phenotypic abnormalities Consanguinity among parents

DISORDERS OF AMINO ACID METABOLISM

Hereditary hyperglycinemias

Maple syrup urine disease

The symptoms appear after one week and include poor feeding, lethargy, vomiting, hypertonicity, muscular rigidity, opisthotonos and convulsions. clinical features are due to accumulation of metabolites especially leucine which also leads to hypoglycemia screening tests include ferric chloride

Phenylketonuria (PKU)
Babies with this condition cant metabolize the amino acid phenylalanine Symptoms can include delayed mental or social skills, seizures or tremors, hyperactivity, skin rashes (eczema), small head size, and a musty odor in the child's breath, skin, or urine.

Disorders of Carbohydrate Metabolism

Galactosemia Hereditary fructose intolerance Glycogen storage disease-Type 1 Disaccharidase deficiency

DIAGNOSIS
Complete blood counts. Urinalysis. Blood glucose. Acid-base parameters and electrolytes. Liver enzymes. Lactate and pryuvate levels Plasma ammonia level Plasma carnitine

 Plasma amino acids. Spinal fluid. Specific enzyme studies

Management
The high risk infant should be kept nil orally and given 10 percent dextrose infusion. Metabolic acidosis should be corrected with sodium bicarbonate When blood ammonia level exceeds 600 mg/dl or there is intractable metabolic acidosis, hemodialysis is life saving Arginine or citrulline is given to infants with urea cycle defects

 In patients with mitochondrial encephalopathy

steroid therapy has been shown to reduce

serum lactate and pyruvate levels.

In infants with hyperammonemia, sodium

benzoate 250 mg/kg in 10% dextrose should be

given at a rate of 20 mg/kg over 1-2 hr, followed

by constant infusion of 250-500 mg/kg during

24 hr

Specific therapy
Replacement therapy Reducing accumulation of toxic metabolite. Promoting excretion of toxins Induction of enzymes. Avoidance of certain drugs Gene therapy Organ transplantation

PREVENTION
Carrier screening Prenatal diagnosis Newborn Screening Neonatal Thyroid Screening