12. Inborn Errors Of Metabolism

Front 1

What is an inborn error of metabolism?

Back 1

A genetic condition which impairs the body's ability to metabolize biological substances

Front 2

What are IMDs?

Back 2

Inborn metabolic diseases

Front 3

What define IMDs?

Back 3

Diseases due to the absence, inactivity, or reduced activity of proteins which regulate metabolic pathways

Front 4

What are some examples of metabolic pathways?

Back 4

The Krebs cycle, glycolysis, amino acid catabolism, glycoprotein synthesis, fatty acid oxidation, urea cycle

Front 5

What is Garrod's hypothesis?

Back 5

The idea that having a toxic excess of substrate will cause improper conversion to the intended product, instead producing a different toxic metabolite

Front 6

What are the two effects resulting from substrate excess, according to Garrod's theory?

Back 6

An increase of toxic metabolite and a deficiency of product (structural, energy)

Front 7

How are IMDs classified?

Back 7

By the type of molecule and cell organelle effected, or by the affected metabolic pathway

Front 8

What type of inheritance generally causes IMDs?

Back 8

Autosomal recessive genes

Front 9

What inheritance types can cause IMDs?

Back 9

Autosomal recessive or dominant genes, X-linked disorders, maternal mitochondrial DNA

Front 10

How common are IMDS?

Back 10

Individually rare, collectively common

Front 11

When do most IMDs present?

Back 11

Neonatal period

Front 12

How severe are neonatal IMDs?

Back 12

Generally acute and life-threatening

Front 13

When is it least common for IMDs to present?

Back 13

Adulthood

Front 14

What makes neonatal IMDs hard to detect?

Back 14

Non-specific presentation-- can be mistaken for infection or sepsis

Front 15

What are the 4 broad groups of clinical presentation?

Back 15

Secondary accumulation of toxins, enegy deprivation, liver disfunction with hypoglycemia, dysmorphism

Front 16

What is common in the clinical presentation of IMDs?

Back 16

Overlap of symptoms (4 broad groups)

Front 17

Why is there often a delay in disease onset for infants with IMDs?

Back 17

Because toxin accumulation takes place over 2-3 days before becoming dangerous

Front 18

What are the symptoms of IMD intoxication?

Back 18

Vomiting, lethargy, coma, liver failure, acidsosi, hyperammonemia, hypoglycemia

Front 19

An infant presents with vomiting, rapid breathing, lethargy, dehydration, fever, and weight loss a day or two after birth. What is the most likely cause?

Back 19

Intoxication secondary to an IMD

Front 20

How does an IMD with secondary energy deprivation present?

Back 20

Immediate issues with hypoglycemia, sudden death in neonates

Front 21

What tissues are affected in an IMD with secondary energy deprivation?

Back 21

Metabolically active tissues (liver, muscle, brain)

Front 22

What are the symptoms of an IMD with secondary energy deprivation in older children?

Back 22

Floppiness, heart failure, cardiomyopathy, high lactic acid

Front 23

How is an IMD with secondary energy deprivation treated?

Back 23

Energy supplements (e.g. glucose infusion), frequent eating

Front 24

A young child presents with floppiness, hypoglycaemia, and seizures after not eating for 18 hours. What is the most likely cause?

Back 24

IMD with secondary energy deprivation

Front 25

How does an IMD with secondary liver failure and hypoglycaemia present?

Back 25

Seizures, acidosis and ketosis, hepatomegaly

Front 26

A 6 week old infant presents with vomiting, hepatomegaly, jaundice, and cataracts. What is the most likely cause?

Back 26

Liver failure secondary to an IMD

Front 27

How does an IMD with secondary dysmorphism present?

Back 27

Slow development, abnormal face or body features, hepatomegaly

Front 28

A young child presents with slow development, frequent infections, hepatomegaly, and a deformed face. What is the most likely cause?

Back 28

IMD with secondary dysmorphism

Front 29

Where are most tests for IMDs conducted?

Back 29

The Inherited Metabolic Biochemistry labs at pediatric hospitals, and later genetic laboratories

Front 30

What results of a first line investigation might suggest an IMD?

Back 30

Hypoglycaemia, acidosis, hyperammonia, elevated LFTS, high lactate

Front 31

What types of screening exists for neonates?

Back 31

PKU, MCAD, congenital adrenal hyperplasia, galactosaemia, CF

Front 32

Why must a great amount of suspicion be used when diagnosing IMDs?

Back 32

They are rare enough that there are more likely causes of symptoms in neonates and young children