2G- Inborn Errors of Metabolism

Question 1

What is the most common monogenic disorder of carbohydrate metabolism?

Answer 1

classical galactosemia

Question 2

What enzyme is defective in classical galactosemia?

Answer 2

galactose-1-phosphate uridyl transferase

Question 3

What are some clinical manifestations of classical galactosemia?

Answer 3

failure to thrive, hepatic insufficiency cataracts and developmental delay.

Question 4

Scenario: patient presents with accumulations of urea precursors such as ammonium and glutamine. It’s also noted that this is an X-linked disorder. What enzyme is defective?

Answer 4

ornithine transcarbamylase (OTC deficiency)

Question 5

Van Gierke’s disease is a defective storage disorder of what substance?

Answer 5

glycogen

Question 6

What enzyme is defective in Van Gierke’s disease?

Answer 6

G6 phosphatase

Question 7

Case scenario: baby presents with poor feeding, failure to thrive, hepatic and renal insufficiency and death. It is noted that the baby cannot metabolize fructose properly. What enzyme is defective?

Answer 7

fructose 1,6-bisphophate aldolase

Question 8

What is characteristics about Mucopolysaccharidoses (MPS disorders)?

Answer 8

Caused by a reduced ability to degrade one or more glycosaminoglycans (GAGs)

Question 9

What are some clinical features of Mucopolysaccharidoses (MPS disorders)?

Answer 9

chronic and progressive multisystem deterioration, which causes hearing, vision, joint and cardiovascular dysfunction

Question 10

What enzyme is defective in Phenylketonuria (PKU)

Answer 10

Mutation of phenylalanine hydroxylase (PAH)

Question 11

What is defective to cause Gaucher disease?

Answer 11

acid β-glucosidase

Question 12

What are the clinical characteristics of Gaucher disease?

Answer 12

visceromegaly, multiorgan failure, and debilitating skeletal disease.

Question 13

What is defective in I-cell disease?

Answer 13

recognition marker of mannose-6-phoshate causing partially degraded oligosaccharides, lipids and glycosaminoglycans

Question 14

What are the clinical manifestations in I-cell diesase?

Answer 14

coarse facial features, skeletal abnormities, corneal opacities, mental retardation and early death

Question 15

What is defective in cystinuria disease?

Answer 15

Caused by abnormal cystine transport between cells and the extracellular environment cause cystinuria

Question 16

Which AA’s are secreted in high amounts in the urine in cystinuria?

Answer 16

cystine, lysine, arginine and ornithine

Question 17

What are the clinical manifestations in cystinuria disease?

Answer 17

kidney stones

Question 18

What is defective in Wilson’s disease?

Answer 18

excess of copper caused by defective excretion of copper into the biliary tract

Question 19

What are the clinical manifestations in Wilson’s diesase?

Answer 19

causes progressive liver disease and neurological abnormalities. It is an autosomal recessive disorder. Patients with Wilson’s usually present with acute or chronic liver disease in childhood. Adults develop neurological symptoms such as dysarthria (inability to correctly articular words) and diminished coordination. One of the characteristic is the finding in the eye- Kayser-Fleischer ring

Question 20

What is defective in MCAD disease?

Answer 20

deficiency of medium-chain acyl-coenzyme dehydrogenase (MCAD)

Question 21

What are the clinical manifestations in MCAD disease?

Answer 21

episodic hypoglycemia, which is often provoked by fasting

Question 22

What is defective in hemochromatosis?

Answer 22

disorder of iron metabolism in which excessive iron is absorbed in the small intestine and then accumulates in a variety of organs such as the liver, kidney, heart, joints and pancreas. It’s a defect in the regulation of transport

Question 23

What type of genetic disorder is hemochromatosis?

Answer 23

Autosomal recessive

Question 24

What are the clinical manifestations in hemochromatosis?

Answer 24

delayed age on onset of fatigue, joint pain, diminished libido, diabetes, increased skin pigmentation, cardiomyopathy, liver enlargement and cirrhosis.

Question 25

What is defective in Congenital adrenal hyperplasia (CAH)?

Answer 25

95% of CAH is caused by mutation in CYP21A2, the gene that encodes 21-hydroxylase

Question 26

What are the clinical manifestations in CAH?

Answer 26

cortisol deficiency, variable deficiency of aldosterone and an excess of androgen

Question 27

What is defective in Maple syrup urine disease?

Answer 27

Defect in branched-chained α-ketoacid dehydrogenase(BCKAD)

Question 28

Which AA's are branched chain?

Answer 28

Valine, Leucine and isoleucine

Question 29

What are the clinical manifestations in Maple syrup urine disease?

Answer 29

Without treatment, accumulation of BCAAs and their associated ketoacids leading to progressive neurodegeneration and death

Question 30

What is defective in Zellwegger syndrome?

Answer 30

It is caused by mutations in genes that encode peroxins. These proteins are necessary both for peroxisome biogenesis and for importing proteins of the peroxisomal matrix and membrane

Question 31

What are the clinical manifestations in Zellwegger syndrome?

Answer 31

It shows in newborn as severe hypotonia, progressive disease of the white matter of the brain, a distinctive facial appearance and typically death in infancy

Question 32

Which populations are at risk for Hereditary hemochromatosis?

Answer 32

more common in northern European (one of every 8)