Persistent Hypoglycemia, Newborn, N/IICU — Metabolic Diseases — Clinical Pathway: ICU

Newborn Persistent Hypoglycemia Clinical Pathway — N/IICU

Metabolic and Endocrine Disorders

This information is intended as a brief summary. Treatment of these conditions should be in consultation with Endocrine or Metabolic specialists.

Condition Etiology Clinical Presentation Treatment Additional Information
Hyperinsulinism
Fatty Acid Oxidation Disorders
  • Carnitine deficiency
  • Fatty acid transport defects
  • Defects of beta-oxidation enzymes
  • Defect of ketone synthesis (HMG-CoA synthase, HMG-CoA lyase)
  • Hypoketotic hypoglycemia,
  • Lethargy
  • Hypotonia
  • Persistent vomiting
  • Hepatomegaly
  • Cardiomyopathy
  • Rhabdomyolysis
  • Reye syndrome-like episodes
  • Avoidance of fasting Aggressive medical management during illness with IV glucose (5 to 10 mg/kg per minute) to increase plasma glucose > 120 mg/dL and to increase plasma insulin (increased plasma insulin concentration suppresses lipolysis and proteolysis).

Rare, but severe

  • All states include MCAD deficiency screening on their newborn screen; many other FAO disorders included in NJ and PA screens
Hypopituitarism
  • Abnormalities of pituitary gland development and/or function – both growth hormone and cortisol deficiency alone or in combination may present with hypoglycemia in the newborn
  • In the newborn it may present with hypoketotic hypoglycemia that mimics hyperinsulinism. In infants and older children presents with growth failure (if growth hormone deficiency) and ketotic hypoglycemia
  • Clues to the diagnosis include evidence of midline defects: cleft lip and/or palate, micropenis
  • Hormonal replacement: Growth hormone 0.2-0.3 mg/kg/week SQ divided in 1-2 doses daily
  • Hydrocortisone: 10-15 mg/m2/day PO for daily replacement. Stress dose 3-4 times the daily dose
  • Brain MRI should be performed as part of the diagnostic evaluation
  • Other pituitary function should be evaluated including thyroid function
Organic Acidemias
  • Maple syrup urine disease
  • Included in newborn screen
    • Normal at birth; by D#4, lethargy, irritability, apnea, hyper/hypotonia, seizures, poor feeding, vomiting, tachypnea
      • ketoacids in urine ≥ maple syrup odor
  • Propionic academia
  • Methylmalonic aciduria
  • Glutaric aciduria
  • Tyrosinemia
  • Presents during the newborn period, after initial period of well-being
  • Life-threatening episodes of metabolic acidosis (increased anion gap); mimics sepsis
  • Associated with significant mortality if unrecognized
  • Usually have associated failure to thrive and developmental delay
  
  • Many included in NJ and PA state screening
  • Hypoglycemia appears to be related to:
    • Liver disease (tyrosinemia)
    • Protein malnutrition (maple syrup urine disease)
Glycogen Storage Disorders
  • A group of disorders in which there is a defect in the pathways of either making glycogen, or breaking down glycogen, or converting glycogen into glucose
  • Glycogen storage disease type 1 is the most severe type. Typical presentation is of severe hypoglycemia and lactic acidosis with a very short fasting tolerance (> 2hrs). In addition, triglycerides, cholesterol and uric acid are elevated. Liver is markedly enlarged. In all other types associated with hypoglycemia (0,3,6 and 9), the pattern of hypoglycemia is of ketotic hypoglycemia. The liver is enlarged in all of these types except GSD type 0.
  • IV dextrose, continuous feedings, cornstarch, limited fasting
Fructose-1,6-biphosphate Deficiency (Baker’s Disease)
  • Impaired gluconeogenesis
  • Glycogenolysis is not affected
  • (therefore, hypoglycemia occurs only during caloric restriction and glycogen accumulation does not occur, so liver involvement is minimal)
  • Failure to thrive; Fasting-induced hypoglycemia, lactic acidosis, ketosis, hyperlipidemia, and hyperuricemia.
  • Diagnosis is supported by provocative testing (glycemic response seen after administration of galactose, but not with fructose, alanine, or glycerol)
  • High-carbohydrate diet and frequent feeding
  • Glucagon administration produces a rise in plasma glucose only in the immediate postprandial period
Conditions with Positive Reducing Sugars
Condition Etiology Clinical Presentation Treatment Additional Information
Hereditary Fructose Intolerance
  • Incidence 1:20,000 (autosomal recessive)
  • Diagnostics: if Clinitest positive, then thin-layer chromatographic separation for confirmation
  • Rarely presents in the first few months of life unless infant has been put on sucrose/fructose containing feeds.
  • Most cases present with recurrent hypoglycemia and vomiting at the age of weaning, when fructose or sucrose typically is added to the infant diet. However, some infants may present earlier because many commercial formulas and medications contain sucrose.
  • Vomiting, hypoglycemia, failure to thrive, cachexia, hepatomegaly, jaundice, coagulopathy, coma, renal Fanconi syndrome, severe metabolic acidosis, lactic acidosis, fructosuria, aminoaciduria, low or absent urine ketones
  • Elimination of dietary fructose, sorbitol, and sucrose can be both diagnostic and therapeutic
  • Homozygous neonates remain clinically well until ingestion of fructose; some formulas (soy) contain sucrose (fructose-glucose disaccharide) that may cause symptoms.