Inborn Errors of Metabolism (IEM)

"Inborn errors of metabolism are rare genetic disorders in which the body cannot properly turn food into energy. The disorders are usually caused by defects in specific proteins (enzymes) that help break down (metabolize) parts of food. A food product that is not broken down into energy can build up in the body and cause a wide array of symptoms. Several inborn errors of metabolism cause developmental delay if not controlled." (NIH, 2015)
CLASSIFICATIONS
Carbohydrates:
  • Carbohydrate metabolism (e.g. glycogen storage disease)
  • Lysosomal storage disorders (e.g. Gaucher's disease, Niemann Pick disease)
  • Peroxisomal function (e.g. Zellweger syndrome)
Proteins:
  • Amino acid metabolism (e.g. phenylketonuria, maple syrup urine disease, glutaric acidemia)
  • Urea Cycle Disorder (e.g. Carbamoyl phosphate synthetase I deficiency)
Fats:
  • Fatty acid oxidation and mitochondrial metabolism (e.g. medium-chain acyl-coenzyme A dehydrogenase deficiency - MCADD)
Trace Elements:
  • Metal metabolism disorders (e.g. hemochromatosis, Wilson’s disease)
Other:
  • Steroid metabolism (e.g. lipoid congenital adrenal hyperplasia, congenital adrenal hyperplasia)
  • Mitochondrial function (e.g. Kearns-Sayre syndrome)
  • Organic acid metabolism or organic acidurias (e.g. alcaptonuria, 2-hydroxyglutaric acidurias)
  • Porphyrin metabolism (e.g. acute intermittent porphyria)
  • Purine or pyrimidine metabolism (e.g. Lesch-Nyhan syndrome)
Good summaries can be found at:
  • Up-to-Date article on IEM
  • UCSF Intensive Care Nursery House Staff Manual on the IEM
  • Approach to IEM, by Learn Pediatrics

Screening & Assessment

**symptom onset with institution of feedings or formula change
  • Family or personal hx: Screen for possible consanguinity, mental retardation, cancers, or SIDS
  • General: history of growth disturbances, weight loss, lethargy
  • HEENT: issues with vision and hearing, dental abnormalities
  • Neuro: seizures, unusual pain reactions
  • Skin: rash, abnormal pigmentation, abnormal hair growth, lumps and bumps
  • GI: Recurrent emesis, diarrhea, pain, poor feeding
  • GU: swelling in extremities, dehydration, excessive urination
  • CV: low or high BP, history of CV complications
  • Resp: Excessive breathing or hyperventilation, apnea or tachypnea
  • Endo: precocious puberty, delayed puberty
  • Psych: Abnormal behavior, depression, psychosis
  • MSK: muscle weakness, cramps, developmental delays
Objective:
  • General: lethargy, dysmorphia, unusual odor, failure to thrive
  • Resp: tachypnea or apnea
  • MSK: hypertonicity, hypotonicity,  joint pain
  • Abdomen: hepatosplenomegaly
  • GI: liver enlargement, jaundice
  • GU: ambiguous genitalia
  • Skin: rashes or patchy hypopigmentation, 
  • HEENT: ocular findings (cataracts, lens dislocation or pigmentary retinopathy)
  • Endocrine: Hypothyroidism, adrenal insufficiency, hypogonadism, diabetes mellitus
Laboratory findings: 
  • metabolic acidosis with increased anion gap
  • primary respiratory alkalosis
  • hyperammonemia
  • hypoglycemia, ketosis or ketonuria
  • low BUN
  • hyperbilirubinemia
  • lactic acidosis
  • high lactate/pyruvate ratio
  • non-glucose-reducing substances in urine
  • elevated liver function tests including PT and PTT
  • neutropenia and thrombocytopenia
  • intracranial hemorrhage

Articles and Position Papers

AAFP's "Inborn Errors of Metabolism in Infancy and Early Childhood: An Update" (2006) -- really good chart of sx and associated disorders, as well as recommendations.

Resources

  • Acute Intermittent Porphyria (AIP): Help with diagnosis, Visit American Porphyria Foundation
  • National PKU Alliance: http://www.npkua.org​