Biochem - Metabolism (Lysosomal storage diseases) Flashcards

Pg. 114 in First Aid 2014 Sections include: -Lysosomal storage diseases

1
Q

In general, what causes lysosomal storage diseases? What general effect do they have?

A

Each is caused by deficiency in one of the many lysosomal enzymes. Results in an accumulation of abnormal metabolic products.

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2
Q

What are 2 major categories of lysosomal storage diseases?

A

(1) Sphingolipodoses (2) Mucopolysaccharidoses

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3
Q

Name 6 examples of sphingolipodoses.

A

(1) Fabry disease (2) Gaucher disease (3) Niemann-Pick disease (4) Tay-Sachs disease (5) Krabbe disease (6) Metachromatic leukodystrophy

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4
Q

Name 2 Mucopolysaccharidoses.

A

(1) Hurler syndrome (2) Hunter syndrome

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5
Q

What are 3 clinical findings of Fabry disease?

A

(1) Peripheral neuropathy of hands/feet, (2) angiokeratomas, (3) cardiovascular/renal disease

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6
Q

What are the deficient enzyme and accumulated substrate in Fabry disease?

A

DEFICIENT ENZYME: alpha-galactosidase A; ACCUMULATED SUBSTRATE: ceramide trihexoside

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7
Q

What is the mode of inheritance for Fabry disease?

A

XR

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8
Q

What is the most common lysosomal storage disease?

A

Gaucher disease

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9
Q

What are 5 clinical findings of Gaucher disease?

A

(1) Hepatosplenomegaly, (2) Pancytopenia, (3) Aseptic necrosis of femur, (4) Bone crises, (5) Gaucher cells (lipid-laden macrophages resembling crumpled tissue paper)

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10
Q

What is the treatment for Gaucher disease?

A

Treatment is recombinant glucocerebrosidase

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11
Q

What are Gaucher cells, and how do they appear on histology?

A

Gaucher cells (lipid-laden macrophages resembling crumpled tissue paper)

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12
Q

What are the deficient enzyme and accumulated substrate in Gaucher disease?

A

DEFICIENT ENZYME: Glucocerebrosidase (Beta-glucosidase); ACCUMUALTED SUBSTRATE: Glucocerebroside

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13
Q

What is the mode of inheritance of Gaucher disease?

A

AR

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14
Q

What are 4 clinical findings of Niemann-Pick disease?

A

(1) Progressive neurodegeneration, (2) Hepatosplenomegaly, (3) “Cherry-red” spot on macula, (4) Foam cells (lipid-laden macrophages)

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15
Q

What are the deficient enzyme and accumulated substrate in Niemann-Pick disease?

A

DEFICIENT ENZYME: Sphingomyelinase; ACCUMULATED SUBSTRATE: Sphingomyelin; Think: “NO MAN PICKS (Niemann-Pick) his nose with his SPHINGer (Sphingomyelinase).”

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16
Q

What is the mode of inheritance for Niemann-Pick disease?

A

AR

17
Q

What are 4 clinical findings of Tay-Sachs disease? What negative clinical finding distinguishes Tay-Sachs from another lysosomal storage disorder, and what is that disorder?

A

(1) Progressive neurodegeneration, (2) Developmental delay, (3) “cherry-red” spot on macula, (4) lysosomes with onion skin; No hepatomegaly (vs. Niemann-Pick)

18
Q

What are the deficient enzyme and accumulated substrate in Tay-Sachs disease?

A

DEFICIENT ENZYME: Hexosaminidase A; ACCUMULATED SUBSTRATE: GM2 ganglioside; Think: “Tay-SaX lacks heXosaminidase”

19
Q

What is the mode of inheritance for Tay-Sachs disease?

A

AR

20
Q

What are 4 clinical findings of Krabbe disease?

A

(1) Peripheral neuropathy (2) Developmental delay (3) Optic atrophy (3) Globoid cells

21
Q

What are the deficient enzyme and accumulated substrate(s) in Krabbe disease?

A

DEFICIENT ENZYME: Glactocerebrosidase; ACCUMULATED SUBSTRATE(S): Galactocerebroside, Psychosine

22
Q

What is the mode of inheritance for Krabbe disease?

A

AR

23
Q

What are 2 clinical findings of Metachromatic leukodystrophy?

A

(1) Central and peripheral demyelination with ataxia, (2) Dementia

24
Q

What are the deficient enzyme and accumulated substrate in Metachromatic leukodystrophy?

A

DEFICIENT ENZYME: Arylsulfatase A; ACCUMULATED SUBSTRATE: Cerebroside sulfate

25
Q

What is the mode of inheritance for Metachromatic leukodystrophy?

A

AR

26
Q

What are 5 clinical findings of Hurler syndrome?

A

(1) Developmental delay, (2) Gargoylism, (3) Airway obstruction, (4) Corneal clouding, (5) Hepatosplenomegaly

27
Q

What are the deficient enzyme and accumulated substrate

A

DEFICIENT ENZYME: Alpha-L-iduronidase; ACCUMULATED SUBSTRATE: Heparan sulfate, Dermatan sulfate

28
Q

What is the mode of inheritance of Hurler syndrome?

A

AR

29
Q

What are 2 clinical findings of Hunter syndrome? What negative clinical finding helps to distinguish it from another lysosomal storage disorder, and what disorder is that?

A

(1) Mild Hurler (which is characterized clinically by development delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly) + (2) aggressive behavior; No corneal clouding (v. Hurler syndrome); Think: “HUNTERs see clearly (no corneal clouding) and aggressively aim for the X (X-linked recessive)”

30
Q

What are the deficient enzyme and accumulated substrate in Hunter syndrome?

A

DEFICIENT ENZYME: Iduronate sulfatase; ACCUMULATED SUBSTRATE: Heparan sulfate, Dermatan sulfate

31
Q

What is the mode of inheritance for Hunter syndrome?

A

XR; Think: “HUNTERS see clearly (no corneal clouding) and aggressively aim for the X (X-linked recessive).”

32
Q

Draw a diagram depicting the metabolic steps blocked by the 6 major sphingolipidoses.

A

See p. 114 in First Aid 2014 for visual at bottom of page

33
Q

In what patient population do Tay-Sachs, Niemann-Pick, and some forms of Gaucher disease have an increased incidence?

A

Increased incidence of Tay-Sachs, Niemann-Pick, and some forms of Gaucher disease in Ashkenazi Jews.