Pocket Pediatrics: The Massachusetts General Hospital for Children Handbook of Pediatrics (Pocket Notebook Series), 2 Ed.



• Inherited enzyme mutation alters metabolism → excess or lack of certain metabolites


• 1:1,400–200,000 live births; NBS screens for many of the disorders

Neonatal Presentation (Pediatr Rev 2009;30:131; Pediatrics 1998;102:E69; Vademecum Metabolicum 2004:3)

• Sx at 24–72 hr of life; prior, mother’s metabolism eliminates metabolic intermediates

• Ill infant w/ nonspecific sx: Lethargy, diff feeding, vomiting, abn resp, hypotonia and szrs, see the acute presentation differential table below

• Abnormal body or urinary odor

• MSUD: Urine smells of maple syrup or burnt sugar

• Isovaleric acidemia and glutaric acidemia type II → pungent, “sweaty feet” odor

Late Presentation (Crit Care Clin 2005;21:S9; Vademecum metabolicum 2004:3)

• >28 d of life; recurrent vomiting, lethargy, or fasting → coma with nonfocal neuro exam, liver dysfxn + mental status changes: Consider urea cycle disorders (UCD)

Adolescent/Adults Presentation (J Inherit Metab Dis 2007;30:631)

• Psychiatric d/o, often w/ additional recurrent rhabdo, myoglobinuria, cardiomyopathy

• Acute cyclic confusion → urea cycle defect, porphyria, homocysteine remethylation defect

• Chronic psych sx → homocystinuria, Wilson dz, adrenoleukodystrophy, lysosomal d/os

• Mild mental retardation & personality Δ → homocystinuria, nonketotic hyperglycemia

Specific Triggers of Decompensation (Vademecum Metabolicum 2004:3)

• Vomiting, fasting, infection, fever, vaccinations, surgery, accident or injury, changes in diet → protein or carbohydrate metabolism disorders

• High-protein diet and/or catabolic state → aminoacidopathies, organic acidemia, UCD

• Fruit, sugar (sucrose), liquid medicines → fructose intolerance

• Lactose → galactosemia

• High fat → fatty acid oxidation disorders

• Drugs → porphyria, glucose-6-phosphate-dehydrogenase deficiency

• Extensive exercise → disorders of fatty acid oxidation, glycolysis, respiratory chain

Differential Diagnosis based on Initial Presentation

LA, lactic acidosis; AG, anion gap; Hypoglyc, hypoglycemia; HypoNa,: hyponatremia; HoTn, hypotension; dz, disease. Adapted from Pediatr Rev 2009;31:131