L16 - Inborn Errors of Metabolism

Question 1

What are Inborn Errors of Metabolism?

Answer 1

a group of rare genetic disorders that result from a block to an essential pathway in the body’s metabolism

Question 2

What occurs as a result of inborn errors of metabolism?

Answer 2

• toxic accumulation of substrates
• toxic accumulation of intermediates from alternative metabolic pathways
• defects in energy production/use due to deficiency of products

Question 3

Describe Alkaptonuria as an IEM?

Answer 3

• black urine on standing
• black ochrontic pigmentation of cartilage and collagenous tissue
• homogentisic acid oxidase deficiency
• autosomal recessive disease
• congential

Question 4

Describe the main features of an IEM?

Answer 4

• autosomal recessive
• autosomal dominant
• X linked
• mitochondrial

Question 5

What is Heteroplasmy?

Answer 5

when the cell contains varying amounts of normal mitochondrial DNA and also mutated DNA

Question 6

What 3 groups are IEM classed into?

Answer 6

• TOXIC ACCUMULATION (protein metabolism, carb intolerance)
• DEFICIENCY IN ENERGY PRODUCTION/USAGE (fatty acid oxidation, mitochondrial disorders)
• DISORDERS OF COMPLEX MOLECULES (lysosomal storage disorders, peroxisomal disorders)

Question 7

What are some clinical features of Neonates with IEM?

Answer 7

• may be born at term at normal birth weight and no abnormal features
• symptpms may present in the 1st week of life when starting full milk feeds
• lethargy, vomiting, poor feeding
• profound hypotonia
• dysmorphic features
• organomegaly

Question 8

What are some biochemical abnormalities of Neonates with IEM?

Answer 8

• hypoglycaemia
• hyperammonaemia
• metabolic acidosis
• lactic acidosis

Question 9

What is Tyrosinaemia Type 1?

Answer 9

genetic deficiency of fumarylacetoacetase (FAH), which catalyses the final step in tyrosine metabolism
increased byproduct succinylacetone leads to significant organ toxicity

Question 10

What is Ornithine transcarbamylase deficiency?

Answer 10

urea cycle disorder
may lead to profound neuropsychiatric manifestations
high protein load can trigger