Metabolic Diseases in Acidotic Newborns
Metabolic Diseases in Acidotic Newborns: Excerpt from The 5-Minute Pediatric Consult
Ralph J. DeBerardinis, MD, PhD
Sulagna C. Saitta, MD, PhD
Metabolic Diseases in Acidotic Newborns - BASICS
Metabolic Diseases in Acidotic Newborns - description
Inborn errors of metabolism are inherited defects in biochemical pathways affecting fats, amino acids, or carbohydrates. Many affect the conversion of fuel to energy. Some present with catastrophic neonatal metabolic acidosis. Because these conditions are life threatening if not treated promptly, a high degree of suspicion 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 Acidotic Newborns - risk factors
Metabolic Diseases in Acidotic Newborns - genetics
Generally autosomal recessive. Exceptions include pyruvate dehydrogenase deficiency (a form of lactic acidosis, usually X linked) and diseases of the mitochondrial genome (maternally inherited).
Metabolic Diseases in Acidotic Newborns - pathophysiology
- Inborn errors of metabolism presenting with metabolic acidosis usually produce an elevated anion gap owing to accumulation of an acidic intermediate. Identification of this acid is the 1st step in establishing the diagnosis.
- Tissue dysfunction results from toxicity of the accumulated by-product and/or failure to produce sufficient energy to meet cellular needs.
- CNS toxicity results in increased intracranial pressure, emesis, lethargy, coma, seizures, abnormalities in muscle tone.
- Hepatic toxicity causes jaundice, failure to thrive, hypoglycemia, hyperammonemia, coagulopathy.
- Other organ systems may be involved, depending on the disease. These include the heart, the proximal renal tubule, the pancreas, and the bone marrow (see below).
Metabolic Diseases in Acidotic Newborns - etiology
Inherited defects in biochemical pathways affecting fats, amino acids, or carbohydrates
Metabolic Diseases in Acidotic Newborns - DIAGNOSIS
Metabolic Diseases in Acidotic Newborns - signs & symptoms
Metabolic Diseases in Acidotic Newborns - history
- Complications with the pregnancy: Some inborn errors of metabolism, particularly certain disorders of fatty acid oxidation, are associated with fatty liver of pregnancy or the HELLP (hypertension, elevated liver enzymes, low platelets) syndrome.
- Current diet and feeding schedule (does baby wake spontaneously to feed?): Acidotic episodes may be triggered by specific exposures or by prolonged fasting, including relatively short delays. In addition, diets low in protein content may delay the onset of symptoms in disorders of amino acid metabolism.
- Unusual odors: Some organic acids are associated with specific odors.
- Family history: Because inborn errors of metabolism are genetic disorders, there may be a family history of poorly explained pediatric death. Diagnoses to inquire 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.
Metabolic Diseases in Acidotic Newborns - physical exam
- ABCs and vital signs: Cushing’s triad (apnea, bradycardia, hypertension) should prompt immediate evaluation for elevated intracranial pressure. Are there signs of dehydration?
- Skin: Jaundice owing to liver toxicity occurs in many neonates with inborn errors of metabolism. Rashes are associated with biotinidase deficiency.
- Head, eyes, ears, nose, throat: Bulging fontanelle suggests elevated intracranial pressure. Minor dysmorphic features (e.g., frontal bossing, short/upturned nose, long philtrum, low-set ears) are sometimes seen in pyruvate dehydrogenase deficiency and severe disorders of fatty acid oxidation.
- Respiratory: Tachypnea may result from either respiratory compensation of metabolic acidosis or from hyperammonemia.
- Cardiovascular: Arrhythmias or signs of heart failure may signal a cardiomyopathy.
- GI: Hepatomegaly occurs in many inborn errors of metabolism that also cause acidosis. It can be the result of abnormal accumulation of lipid or glycogen. Abdominal pain and emesis can be caused by ketosis.
- Neurologic: Inborn errors of metabolism presenting with acidosis are often associated with neuronal toxicity. Every neonate with a suspected inborn error of metabolism must have a complete neurologic exam.
- Assessment for odors:
- Burnt sugar: Maple syrup urine disease
- Fruity: Ketosis
- Sweaty feet: Isovaleric acidemia
- Growth parameters: Normal at birth for most inborn errors of metabolism
Metabolic Diseases in Acidotic Newborns - tests
Metabolic Diseases in Acidotic Newborns - lab
The goal of the lab evaluation is to make a presumptive diagnosis as soon as possible. In most cases, definitive diagnosis requires specialized and time-consuming tests. 2 critical management points:
Metabolic Diseases in Acidotic Newborns - differencial diagnosis
In neonates, many different inborn errors of metabolism present with similar symptoms, which can easily be confused with other serious diseases.
- Differential diagnosis in sick, acidotic neonate:
- Sepsis
- Congenital heart disease
- Toxin/Drug exposure
- Perinatal depression
- Inborn error of metabolism
- Categories of inborn error of metabolism presenting with neonatal acidosis:
- Lactic acidosis:
- Pyruvate dehydrogenase deficiency
- Pyruvate carboxylase deficiency
- Phosphoenolpyruvate carboxykinase deficiency
- Defects in tricarboxylic acid cycle enzymes
- Mitochondrial diseases or other conditions affecting oxidative phosphorylation
- Severe disorders of gluconeogenesis (e.g., glucose-6-phosphatase deficiency)
- Multiple carboxylase deficiency, biotinidase deficiency
- Disorders of fatty acid oxidation
- Ketoacidosis:
- Disorders of ketone utilization (e.g., β-ketothiolase deficiency)
- Ketosis can also occur in lactic acidosis syndromes (above) and organic acidemias (below)
- Other organic acids:
- Maple syrup urine disease
- Branched chain organic acidurias (methylmalonic acidemia, propionic acidemia, isovaleric acidemia)
- Many others. Note that in some cases, other abnormalities (e.g., lethargy, hyperammonemia) may occur prior to severe acidosis.
Metabolic Diseases in Acidotic Newborns - TREATMENT
Metabolic Diseases in Acidotic Newborns - general measures
Metabolic derangement usually worsens during times of stress (e.g., perinatal period, infection, fasting) and accompanying catabolism. Provide sufficient calories to reverse the catabolic state. Considerations include:
- IV access
- Many decompensated patients will have altered mental status and dehydration. Consider intubation if obtunded.
- Bicarbonate boluses and infusions may be necessary, especially if pH <7.22 or bicarb <14. Monitor sodium carefully in patients receiving NaHCOIn most cases, a high glucose infusion rate (e.g., with D10-based fluid) speeds stabilization. One important exception is pyruvate dehydrogenase deficiency, a primary lactic acidosis syndrome, in which rapid glucose infusion can worsen the lactic acidosis. These children should receive D5.
- Specific dietary measures require a presumptive diagnosis.
- Total parenteral nutrition is a useful option when a presumptive diagnosis has been made. Note that special amino acid mixtures are available for particular disorders (e.g., maple syrup urine disease).
- Insulin can be used to reverse states of severe catabolism.
- Nasogastric feeding using appropriate formulas is useful.
- In patients with large acid load and/or concomitant hyperammonemia, hemodialysis may be indicated.
Metabolic Diseases in Acidotic Newborns - special therapy
Specific therapies are best carried out with the help of a biochemical geneticist or other specialist with experience treating inborn errors of metabolism, and a clinical nutritionist.
- Organic acidemias:
- Protein restriction, protein elimination during times of stress, and avoidance of fasting
- High glucose infusion rates during decompensation
- Primary lactic acidosis syndromes: Therapy is supportive and involves avoidance of stresses such as fasting.
- In pyruvate dehydrogenase deficiency, a ketogenic diet may improve chronic acidosis.
- Fatty acid oxidation disorders: Low-fat, high-carbohydrate diets with frequent feeds
Metabolic Diseases in Acidotic Newborns - FOLLOW UP
Metabolic Diseases in Acidotic Newborns - complications
- Failure to treat patients promptly can be fatal or result in severe CNS insult and developmental disability. The basal ganglia are particularly susceptible to a variety of metabolic disturbances, and damage to these structures can cause “metabolic stroke.”
- For many inborn errors of metabolism, recurrent episodes of acidosis, triggered by stress, intercurrent illness, or dietary noncompliance, are a major source of morbidity.
- Long-term effects may include progressive tissue dysfunction (e.g., liver or renal failure, cardiomyopathy) or failure to thrive.
Metabolic Diseases in Acidotic Newborns - bibliography
Burton BK. Inborn errors of metabolism in infancy: A guide to diagnosis. Pediatrics. 1998;102:E69–E77.
Ozand PT, Gascon GG. Organic acidurias: A review. Part 1. J Child Neurol. 1991;6:196–219.
Ozand PT, Gascon GG. Organic acidurias: A review. Part 2. J Child Neurol. 1991;6:288–303.
Saudubray JM, Ogier de Baulny H, Charpentier C. In: Fernandes J, Saudubray JM, Van den Berghe G, eds. Inborn Metabolic Diseases: Diagnosis and Treatment. 3rd ed. New York: Springer Verlag; 2000.
Metabolic Diseases in Acidotic Newborns - CODES
Metabolic Diseases in Acidotic Newborns - icd9
- 270.3 Branched chain amino acids disturbances
- 270.3 Maple syrup urine disease
- 277.87 Mitochondrial encephalopathy
Metabolic Diseases in Acidotic Newborns - FAQ
- Q: If an infant dies before a diagnosis is made, what can be done to provide information for family members regarding future pregnancies?
- A: Postmortem examination and biochemical tests on tissues obtained immediately after death can establish the diagnosis. Skin biopsy (obtained premortem or postmortem) yields fibroblasts for a variety of biochemical assays. Workup of primary lactic acidosis syndromes requires electron transport chain analysis of muscle, which must be harvested within 30 minutes after death.
- Q: What determines developmental outcome in children with inborn errors of metabolism?
- A: Disease severity depends in part on the specific mutations in each patient. However, prompt initiation of appropriate therapy in the newborn period as well as compliance with chronic management and avoidance of decompensation periods all contribute to developmental outcome.
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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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