Inborn Errors of Metabolism

Question 1

A patient of Ashkenazi Jewish heritage presents with Hepatosplenomegaly and failure to thrive.

What is the disease?
What is the defect?

Answer 1

NPD type A

Acid sphingomylinas e deficiency

The patient will also present with progressive neurologic symptoms.
Niemann-Pick ells are enlarged marophages with cytoplasm distended by vacuoles containing sphingomyelin and cholesterol. They are usually large and rounded

Question 2

A patient presents with hepatosplenomegaly and infiltrative lung disease

common ethnicities:

Answer 2

NPD type B
acid sphingomyelinas e deficiency

Common ethnicities: Ashkenazi Jew, Saudi Arabian, Turkish, Portuguese/Brazilian, English

Question 3

developmental delay, liver dysfunction, neurodegenerative symptoms

Answer 3

NPD type c

Question 4

Hepatosplenomegaly, skeletal abnormalities, bone marrow involvement
ethnicity:

Answer 4

Gaucher’s type 1

Ashkenazi Jew

Question 5

what is the morphology of Gaucher disease (all types)

Answer 5

Accumulated glucocerebrosides in lysosomes of macrophages fill the cytoplasm
macrophages take on the characteristic “wrinkled paper” appearance that reflects the large lysosomes

Question 6

Rapid neurogegenerative course, bone marrow involvement, hepatosplenomegaly, fatal within two years
(pan-ethnic)

Answer 6

Gaucher’s type 2

Question 7

What is deficient in all types of gaucher disease?

Answer 7

Beta-glucocerebrosidase

Question 8

Neurodegeneration, hepatosplenomegaly, bone marrow involvement
Swedish

Answer 8

Gaucher type 3

Question 9

infants:
Severe generalized hypotonia, muscle weakness, hypertrophic cardiomyopathy leading to cardiorespiratory failure usually by 1 year

Answer 9

Pompe Disease- infantile form

Question 10

skeletal myopathy with slowly proressive muscle weakness, markedly increased serum creatine kinase

Answer 10

Pompe Disease- juvenile and adult forms

Question 11

what is the defect of Pompe disease?

Answer 11

Lysosomal glucosidase

Question 12

Sandhoff
what is it?
what is deficient?
ethnicities?

Answer 12

Sandhoff disease is a defect in HexB. it is a severe form of Tay-Sachs and infants with this disease produce no hexosaminidase A or B enzymes that break down fatty acids.
Sandhoff is most common in creole, northern argentinian, saskatchewan, canadian, lebanse

Question 13

an infant presents with feeding problems, unexplained crying, irritability, fever with no infection.
what is the disease?
what is the deficiency?

Answer 13

Krabee
Galactocerebrosidase (GALC)
the disease is a result of damage to myelin of nerve cells. it develops before 6 months and death is within 2 years.

Question 14

what does GALC do?

Answer 14

GALC is responsible for the break down of galactolipids. The build up of galactolipids causes the myelin cells to self- destruct

Question 15

a 3 year old patient presents with gait disturbances, optic atrophy, and diminished deep tendon reflexes.
what is the disease?
what is the deficiency?

Answer 15

Metachromic Leukodystrophy
Sulfatide sulfatase (arylsulfatase A)

Question 16

what is the morphology of Metachromic Leukodystryphy

Answer 16

metachromatic graunules. The central myelination is abnormal with a widespread loss of myelinated oligodendroglia in the CNS and segmental demyelination of the peripheral nerves.
The sulfatide accumulations produce extensive damaze and result in loss of both cognitive and motor functions

Question 17

symptoms usually begin in adolescence or early adulthood. They include exercise intolerance, fatigue, myalgia, muscle cramps, muscle swelling
what is the treatment for this disease?

Answer 17

McArdle’s Disease
Muscle glycogen phosphorylase
High protein diet and oral sucrose before sustained aerobic activity

Question 18

Neurologic dysfunction with self-destructive tendencies
inheritance:
abnormal lab values:

Answer 18

Lesch-Nyhan syndrome
HGPRT
x-linked
increased uric acid levels

Question 19

total cholesterol over 300 mg/dL
disease?
deficiency:
inheritance:
increased risk for?

Answer 19

total cholesterol over 300 mg/dL
disease? familial hypercholesterolemia
deficiency: LDL receptor
inheritance: AD
increased risk for? MI