Resources

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Articles / Journals

Genome.gov
Patient.info
Medlineplus.gov

Latheef, Shaik Abdul. “A database for inborn errors of metabolism in the Indian state of Andhra Pradesh.” Bioinformation 4, no. 7 (2010): 276.

Elshaari¹, F. A., D. S. Sheriff¹, A. E. Agela, A. A. Alshaari, and S. S. Muftah. “Screening for Inborn Errors of Metabolism.”

Clinical Updates

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What is Inborn Error of Metabolism?
YouTUBE.com

Inborn Errors of Metabolism
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What are Inborn Errors of Metabolism?

Metabolism is a sequence of chemical reactions in the cells of the body. These metabolic reactions play a major role in breaking down nutrients and generating and storing energy. Any block in a metabolic pathway can lead to serious consequences.

Inborn errors of metabolism (IEMs) are a group of rare, genetic disorders caused by defects in proteins (enzymes) which help metabolize or break down food into energy. Food products which are not broken down can build up in the body and lead to various types of toxicities. If untreated, IEMs can lead to severe developmental issues and can even be fatal.

IEMs are a frequently occurring group of disorders in India with one in every 2497 newborn being detected with one of the IEMs (Latheef, 2010). In some states like Karnataka, Tamil Nadu and Andhra Pradesh; one in every 1000 newborns is detected with some form of IEM.

IEMs can be broadly categorized into the following:
  • Urea cycle disorder – citrullinemia, argininosuccinic aciduria, argininemia
  • Organic acidemias – maple syrup urine disease, Propionic acidemia, methylmalonic aciduria
  • Amino acidopathies – tyrosinemia, phenylketonuria, homocysteinuria
  • Carbohydrate disorders – galactosemia, fructosemia
  • Mitochondrial disorders – pyruvate dehydrogenase deficiency
Some of the most common IEMs in India include:
  • Fructose intolerance
  • Galactosemia
  • Maple sugar urine disease (MSUD)
  • Phenylketonuria (PKU)
  • Congenital hypothyroidism (CAH)
  • Glucose-6-phosphate-dehydrogenase deficiency (G6PD)
Most IEMs are autosomal recessive disorders which means both parents have the carrier gene with 25% chance of each child having the disease. There are some IEMs which are autosomal dominant and X-linked.
Most IEMs are present at birth though some milder forms may be detected in early adulthood. Some of the features of IEMs include:
  • Infant is sick and does not feed properly
  • Lethargicv
  • May present with seizures
  • Uncontrolled vomiting
  • Jaundice and liver dysfunction
  • Liver enlargement
  • Spleen enlargement
  • Abnormal facial features
  • Skeletal abnormalities
  • Abnormal urine and body odour
If the pediatrician suspects an IEM, he/she will include a range of tests to confirm the diagnosis:
  • general metabolic screening tests – simple tests like urine, blood glucose, acid-base profile, lactate, ammonia and liver function
  • specific metabolic assays – like amino acids, organic acids
  • enzyme studies
  • DNA analysis
Treatment is aimed at preventing complications and enabling independent living. An interdisciplinary team of doctors including pediatricians, neurologists, endocrinologists, nephrologists and physiotherapists will be required to take care of the clinical needs of the child/adult. Early diagnosis is crucial to avoid developmental delays and organ damage. Some of the treatment and management measures include:
  • acute management of the infant involves preventing further build-up of toxic substances. In acute cases, feeds are stopped and 10% dextrose is usually started. Toxic metabolites can be removed by filtration or dialysis
  • diet is the main factor in managing IEMs. The objective is to minimize intake of the toxic metabolite. Special foods are usually available for IEMs which ensure nutrition and extra supplements
  • replacing the missing enzyme, metabolite or cofactor is critical in some cases. Enzyme Replacement Therapy (ERT) is critical for the glycogen storage disorders like Pompe and Fabry disease
  • bone marrow, kidney or liver transplant may be an option in some cases
Children and adults with IEMs must be encouraged to participate in all life activities and must be encouraged to go to regular schools, colleges and participate in social activities. Caregivers must ensure that a strict dietary regimen is maintained. Genetic counselling and psychosocial counselling must be made available whenever required with other supportive measures.

If there is a known case of IEMs in the family, it is absolutely essential for closest female relatives like siblings, uncles, aunts and cousins to test for carrier status.

If a woman with a carrier status is pregnant, prenatal test is essential to determine if the fetus has the disease mutation.