2025 – PAGE 349 – INBORN ERRORS OF METABOLISM & MISCELLANEOUS METABOLIC DISORDERS
INBORN ERRORS OF METABOLISM (IEM) PEARLS
NOTE: Use this section in conjunction with the inborn errors of metabolism table as a quick review of some of the IEMs. A full discussion of each disease will be discussed separately.
INBORN ERRORS OF METABOLISM (PEARLS)
Inborn errors of metabolism usually present with an acute onset of symptoms such as lethargy, vomiting, tachypnea, confusion, or seizures. Look for the ABSENCE of a fever in most of these patients. Keep in mind, though, that galactosemia patients may actually present with gram-negative rod sepsis (especially E. coli).
ORGANIC ACIDEMIAS (PEARLS)
In organic acidemias, an enzyme deficiency leads to difficulty in breaking down certain organic acids from particular amino acids and fatty acids. Look for virtually every lab mentioned in the IEM summary table to be abnormal (hypoglycemia, hyperammonemia, ketoacidosis, and lactic acidosis). Patients can also have thrombocytopenia and granulocytopenia. Patients present EARLY at about DOL 2.
UREA CYCLE DEFECTS (PEARLS)
The primary role of the urea cycle is to clear ammonia (NH3). In urea cycle defects, there is a massive build-up of ammonia, but the rest of the labs are fine! Look for ammonia levels in the hundreds and hypotonia—that’s it! No acidosis, but the patient can possibly have a mild RESPIRATORY alkalosis.
FATTY ACID METABOLISM DISORDERS (PEARLS)
Patients present due to fatty acid metabolism disorders when there is a stressor, or meals are spread out and carbohydrate reserves become depleted. That’s when the inability to metabolize fatty acids due to a disorder results in symptoms. Look for hypoglycemia (because that’s the trigger), metabolic acidosis (lactic acid), and hyperammonemia (from protein breakdown), but NO KETOACIDOSIS because the fatty acids cannot be broken down into ketones!
STORAGE DISEASES (PEARLS)
The storage diseases usually present later in infancy, or early in childhood, with SLOWLY PROGRESSIVE issues. This is because it takes months to years for the intra-organ build-up of metabolites to occur.
- GLYCOGEN STORAGE DISEASES I (GSD I): This presents during fasting, or when a child’s meals have been spread out. In an older child it may present when s/he is sleeping more.
MITOCHONDRIAL DISORDERS (PEARLS)
Elevated lactic acid and pyruvate are great markers for mitochondrial disorders. These disorders have to do with fat or carbohydrate metabolism, and the patients are often dependent on anaerobic metabolism (AKA anaerobic respiration) at the time of presentation. The patient will also have increased URIC ACID because s/he depends on protein for energy. Can have hepatomegaly; if so, think mitochondrial issues = GSD I (+ketones) or FA metabolism (no ketones).
AMINO ACIDOPATHIES (PEARLS)
Amino acidopathies occur when isolated amino acids cannot be broken down. Since the problem is limited to only a particular amino acid, there is no significant elevation in ammonia levels. Also, there is no acidosis because there are no fuel issues (carbohydrate and fat metabolism are working fine).
- MAPLE SYRUP URINE DISEASE(MSUD): This one is an exception and does result in hypoglycemia, hyperammonemia, and acidosis. Symptoms start the very first week and progress to severe neurological issues within 2–3 weeks if left untreated (encephalopathy, seizures). The baby’s urine will smell like maple syrup.