Metabolic Diseases in Hypoglycemic Newborns
Metabolic Diseases in Hypoglycemic Newborns: Excerpt from The 5-Minute Pediatric Consult
Ralph J. DeBerardinis, MD, PhDSulagna C. Saitta, MD, PhD
Metabolic Diseases in Hypoglycemic Newborns - BASICS
Metabolic Diseases in Hypoglycemic Newborns - description
Inborn errors of metabolism are inherited defects in biochemical pathways affecting metabolism of fats, amino acids, or carbohydrates. Some inborn errors of metabolism predispose newborns to hypoglycemia. Because these conditions are life threatening if not treated promptly, maintaining a high degree of clinical suspicion in sick neonates is essential. In the newborn period, the immediate goals should be to:
- Establish a tentative diagnosis.
- Initiate presumptive management.
- Send confirmatory studies.
- Involve a team trained in treating patients with inborn errors of metabolism.
Metabolic Diseases in Hypoglycemic Newborns - risk factors
Metabolic Diseases in Hypoglycemic Newborns - genetics
Almost all inborn errors of metabolism causing hypoglycemia are autosomal recessive. One form of hyperinsulinism is autosomal dominant.
Metabolic Diseases in Hypoglycemic Newborns - pathophysiology
- Through glycolysis and oxidative phosphorylation, glucose is a major source of cellular energy (ATP). Failure to produce ATP is probably the main source of hypoglycemia-associated tissue dysfunction.
- The brain preferentially uses glucose metabolism to produce energy and is particularly sensitive to hypoglycemia.
- A long list of metabolic disturbances in a variety of pathways can result in hypoglycemia.
- Neonates are at particular risk for hypoglycemia because they use glucose more rapidly than adults and have immature ability to obtain energy from other sources (glycogen, muscle protein, adipose tissue).
Metabolic Diseases in Hypoglycemic Newborns - etiology
Inherited defects in biochemical pathways affecting metabolism of fats, amino acids. or carbohydrates
Metabolic Diseases in Hypoglycemic Newborns - DIAGNOSIS
Metabolic Diseases in Hypoglycemic Newborns - signs & symptoms
Metabolic Diseases in Hypoglycemic Newborns - history
- Family history: Because inborn errors of metabolism are genetic disorders, patients may have a family history of poorly-explained pediatric death. Diagnoses to ask about include:
- Sepsis (was an organism identified?)
- Sudden infant death syndrome
- Cardiomyopathy
- Uncontrollable seizures
- Coma
- Liver failure
- Unexplained developmental delay or hypoglycemia in older siblings can provide useful clues.
- Complications with the pregnancy:
- Maternal diabetes
- Certain disorders of fatty acid oxidation, are associated with fatty liver of pregnancy or the HELLP (hypertension, elevated liver enzymes, low platelets) syndrome.
- Results of newborn screen: Children are tested for a variety of inborn errors of metabolism through newborn screening programs. Some of these disorders predispose to hypoglycemia and have specific therapies.
- Current diet and feeding schedule: Timing of hypoglycemia helps form differential diagnosis.
Metabolic Diseases in Hypoglycemic Newborns - physical exam
- ABCs and vital signs: Tachycardia and hypotension are commonly seen in hypoglycemia.
- Facies: Decreased interpupillary diameter or other midline anomalies occur in association with abnormalities of the pituitary.
- Skin: Diaphoresis is an effect of the catecholamine surge that accompanies hypoglycemia.
- Respiratory: Tachypnea may be the result of either respiratory compensation of metabolic acidosis or hyperammonemia.
- GI: Hepatomegaly occurs in many inborn errors of metabolism causing hypoglycemia and is a key feature in differentiating possible diagnoses. It can be a result of abnormal accumulation of lipid (e.g., in fatty acid oxidation defects) or glycogen (e.g., glycogen storage disease).
- Neurologic: Every neonate with a suspected inborn error of metabolism needs a complete neurologic exam to evaluate level of consciousness, tone, unusual movements, reflexes.
- Tremulousness is a common early sign of hypoglycemia.
- Stupor and coma occur if hypoglycemia is not reversed.
- Growth parameters: Infants of diabetic mothers may be large for gestational age. Beckwith-Wiedemann syndrome presents with an infant that is large for gestational age, hyperinsulinism, and physical stigmata (hemihypertrophy, macroglossia, abdominal wall defects).
Metabolic Diseases in Hypoglycemic Newborns - tests
Metabolic Diseases in Hypoglycemic Newborns - lab
The goal of the lab evaluation is to make a presumptive diagnosis as soon as possible. In many cases, definitive diagnosis requires specialized and time-consuming tests. 2 critical management points:
- Presumptive treatment should not await a definitive diagnosis, but should be based on clinical suspicion and initial labs. Delays in treatment can be fatal.
- Involvement of a biochemical genetics team is invaluable in directing the workup of suspected inborn errors of metabolism.
- In a neonate with a hypoglycemic dextrose stick, obtain the following critical labs as soon as possible:
- Basic metabolic profile including glucose
- Urinalysis for ketones: Inappropriately low in hyperinsulinism, fatty acid oxidation defects
- Arterial blood gas with lactate: Lactic acidosis occurs in gluconeogenic defects and in glycogen storage disease type I.
- Insulin: Inappropriately high in hyperinsulinemic states
- Cortisol, growth hormone levels: Inappropriately low in deficiency states
- Plasma acylcarnitine profile: Diagnostic for fatty acid oxidation defects, some organic acidemias
- Urine organic acids: Helps quantify accumulation of ketones and intermediates of amino acid and lipid metabolism
Metabolic Diseases in Hypoglycemic Newborns - differencial diagnosis
Hypoglycemia is caused by increased glucose use or decreased glucose availability. Examples of disorders causing each:
- Increased glucose use:
- Sepsis increases metabolic demand and is a leading cause of neonatal hypoglycemia.
- Hyperinsulinemia
- Decreased insulin counter-regulatory hormones (glucagon, cortisol, growth hormone)
- Decreased glucose availability/production:
- Infants of diabetic mothers
- From ingested carbohydrate: Galactosemia, hereditary fructose intolerance
- Glycogen storage diseases
- Decreased gluconeogenesis: Phosphoenolpyruvate carboxykinase deficiency, fructose-1,6-diphosphatase deficiency, pyruvate carboxylase deficiency
- From decreased efficiency of pathways providing alternate energy sources: Organic acidemias, fatty acid oxidation defects
- Various toxins or medications interfere with pathways needed to maintain glucose homeostasis, including salicylates, valproate, beta-blockers, ethanol, and exogenous insulin.
Metabolic Diseases in Hypoglycemic Newborns - TREATMENT
Metabolic Diseases in Hypoglycemic Newborns - general measures
- A well-appearing neonate with a low dextrose stick should be fed immediately. If feeds are contraindicated or not tolerated, obtain IV access.
- In children with associated physical or laboratory findings consistent with an inborn error of metabolism or other serious illness (e.g., vital sign instability, lethargy, acidosis), intravenous access should be obtained.
- A dextrose bolus (e.g., 5 cc/kg D10) and infusion rapidly corrects hypoglycemia in most cases. Infants requiring high glucose infusion rates are suspicious for hyperinsulinism.
Metabolic Diseases in Hypoglycemic Newborns - special therapy
Specific therapies vary according to the diagnosis and are best carried out with the help of a specialist familiar with each disease. Examples include:
- Hyperinsulinism:
- May require continuous glucose administration (IV or via continuous gastric feeds)
- Medical therapies including diazoxide and octreotide
- Pancreatectomy
- Deficiencies in counter-regulatory hormones: Hormone supplementation
- Galactosemia, hereditary fructose intolerance: Eliminate offending agent from diet.
- Fatty acid oxidation disorders, glycogen storage disease type I, defects in gluconeogenesis: Frequent feeds, fasting avoidance, increase caloric intake during stress
Metabolic Diseases in Hypoglycemic Newborns - FOLLOW UP
Metabolic Diseases in Hypoglycemic Newborns - complications
- Hypoglycemic episodes must be recognized and treated promptly or permanent CNS injury (“hypoglycemic stroke”) may occur.
- For many inborn errors of metabolism, episodes of hypoglycemia may recur. These are avoided by specific dietary measures during times of stress.
Metabolic Diseases in Hypoglycemic Newborns - bibliography
Glasgow AM. Hypoglycemia of infancy and childhood. In: Becker KL, ed. Principles and Practice of Endocrinology and Metabolism. 2nd ed. Philadelphia: JB Lippincott; 1995.Saudubray JM, de Lonlay P, Touati G, et al. Genetic hypoglycaemia in infancy and childhood: Pathophysiology and diagnosis. J Inherited Metab Dis. 2000;23:197.
Metabolic Diseases in Hypoglycemic Newborns - CODES
Metabolic Diseases in Hypoglycemic Newborns - icd9
- 271.0 Glycogenosis Amylopectinosis
- 271.1 Galactosemia
- 271.2 Hereditary fructose intolerance
- 75.0 Syndrome of "infant of a diabetic mother”
Metabolic Diseases in Hypoglycemic Newborns - FAQ
- Q: Why is hypoglycemia dangerous?
- A: Glucose is a crucial source of rapidly available energy for many tissues, especially the brain. Prolonged hypoglycemia causes CNS damage.
- Q: Why are the critical labs so important?
- A: In some metabolic disorders, the biochemical disturbance is apparent only during hypoglycemic episodes. Collecting this panel of informative labs during an episode greatly increases the chance of making a diagnosis.
- Q: If an infant dies before a diagnosis is made, what can be done to provide information for family members regarding future pregnancies?
- A: A postmortem examination and biochemical tests performed on various tissues obtained immediately after death can establish the diagnosis. A skin biopsy (obtained premortem or postmortem) yields fibroblasts for a variety of biochemical assays, including enzyme defects in fatty acid oxidation disorders and organic acidemias. Workup of primary lactic acidosis syndromes requires electron transport chain analysis of muscle, which must be harvested immediately (within 30 minutes) after death.
Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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