Inborn Errors of Metabolism

Metabolism is the process by which our body turns food into energy. There are some conditions in which our body doesn’t turn food into energy. Inborn errors of metabolism are such rare inherited (genetic) disorders. There are hundreds of known IEMs or a large group of rare disorders. These disorders are caused by an inherited deficiency or lack of proteins that have enzymatic, carrier, receptor, or structural roles. Around one child in 1000 live births may have IEMs, but the number may vary greatly.

Inborn Errors of Metabolism (IEM)

Enzymes break down or metabolize foods. These enzymes are specific proteins that are decoded from genes. Defective genes cause defects in certain proteins (enzymes) – which in turn leads to metabolic disorders. A single gene defect can cause block in a metabolic pathway resulting in accumulation of substrate or deficiency of product or absence of a metabolite. Defective metabolism or errors in metabolism cause certain substances and products to build up in the body – which may lead to an array of symptoms.

There are many different types of inborn errors of metabolism.

  • Galactosemia
  • Albinism
  • Cystinuria (a cause of kidney stone)
  • Lactose intolerance
  • Phenylketonuria (PKU)
  • Fructose intolerance
  • Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)
  • Maple syrup urine disease [MSUD]

For instance, some of the symptoms associated with Maple syrup urine disease (MSUD) include lethargy, feeding difficulties, characteristic body odour, seizures and coma. These symptoms manifest during the first week of life.

Typical Symptoms or Warning Signs of IEM include

  • Breathing difficulty (Apnea)
  • Poor feeding
  • Sluggishness (lethargy)
  • Recurrent vomiting
  • Tachypnoea (fast breathing)
  •  Poor growth


A paediatrician or child specialist helps in diagnosing the cause if any infant or a full-term infant is presented with the above signs and symptoms. The doctor will physically and clinically examine the child. Infants and children with IEM are diagnosed through clinical suspicion or newborn screening.

Clinical findings suggestive of Inborn Error of Metabolism include, but not restricted to the following:

  • Recurrent lethargy
  • A history of growth disturbances
  • Mental retardation
  • Seizures
  • Poor feeding
  • Rashes
  • Apnea

Physical findings suggestive of Inborn Errors of Metabolism include the following:

  • Coarse or dysmorphic facial features
  • Rashes or patchy hypopigmentation
  • Eyes findings (pigmentary retinopathy, lens dislocation, cataracts)
  • Unusual odours
  • Jaundice
  • Ambiguous genitalia
  • Hepatosplenomegaly
  • Hypotonicity
  • Hypertonicity
  • Lethargy
  • Tachypnoea
  • Apnea


Newborn screening tests can identify some of these disorders. Timely newborn screening, genetic testing, and biochemical testing are important in early recognition and treatment of these disorders. The presumptive positive results should be confirmed by more definitive laboratory tests.

Laboratory findings

Laboratory finding includes non-glucose reducing substances in the urine, lactic acidosis, hyperbilirubinemia, low BUN, ketosis (ketonuria), hypoglycemia, hyperammonemia, primary respiratory alkalosis and metabolic acidosis; Thrombocytopenia, neutropenia and elevated liver function tests.

Bottom Line

Diagnosis is very important specially in the early infancy. Advancements in the diagnosis and treatment of IEMs is quite promising. Early diagnosis and appropriate treatment show excellent outcomes for many of these Inborn Errors of metabolism. Several inborn errors of metabolism cause developmental delays or other medical problems if they are not controlled.

These disorders, if left untreated, may manifest later in life with devastating symptoms that slowly and gradually become progressive with the involvement of several organs and systems including skin, eyes, kidneys, liver, skeletal muscles and gastrointestinal tract.