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Flashcards in Enzyme Deficiencies Deck (105)
1

What is the causative enzyme for PKU (phenylketonuria)?

phenylalanine hydroxylase (PAH)

2

Which metabolic pathway does Phenylalanine hydroxylase act in?

Amino Acid metabolism
- responsible for converting phenylalanine to tyrosine

3

What is an inborn error of metabolism?

general term for diseases caused by mutations to genes involved with metabolic pathways

4

What precursor builds up in PKU?

phenylalanine which then turns to phenylpyruvic acid

5

How do you treat PKU?

keep on a strict diet low in phenylalanine

6

What enzyme is deficient in Oculocutaneous Albinism?

tyrosinase - necessary for formation of melanin

7

Because of the deficiency of tyrosine in PKU pateints, how to they tend look?

blond hair
blue eyes due to deficiency of melanin

8

Lack of pigment in Oculocutaneous Albinism, leads to what clinical symptoms?

- poor visual acuity
- nystagmus (pendular eye movement)
- underdeveloped fovea

9

What enzyme is deficient in Maple Syrup Urine Disease?

branched-chain ketoacid decarboxylase

(Maple trees have branches.)

10

What is the result of Maple Syrup Urine Disease?

Valine (val), leucine (leu) and isoleucine (ile) are excreted in the urine

11

What symptoms are present in the first week if newborns have Maple Syrup Urine Disease?

vomiting, alternating tone

12

What is the treatment for Maple Syrup Urine Disease?

dietary restriction of val, leu and ile
(still susceptible to deterioration)

13

What is the most common carbohydrate metabolism disorder?

Glucose-6-phosphate dehydrogenase deficiency

14

The glucose-6-phosphate dehydrogenase is responsible for what? pathway?

oxidative steps of the pentose phosphate pathway

15

What inheritance pattern is Glucose-6-phosphate dehydrogenase deficiency?

x-linked recessive

16

Glucose-6-phosphate dehydrogenase deficiency leads to reduced ability to produce _________?

NADPH (potent reducer used by cells to protect against oxidative damage)
-pentose phosphate pathway

17

Which cell type is most affected by Glucose-6-phosphate dehydrogenase deficiency? Why?

RBC no nucleus to provide other reducing sources
susceptible to oxidative damage

-results in anemias

18

What populations are more likely to be affected by Glucose-6-phosphate dehydrogenase deficiency?

African
Asian
Middle Eastern
Mediterranean

19

What are the three main sources for oxidative assaults that would cause symptoms of Glucose-6-phosphate dehydrogenase deficiency?

INFECTION - cold, flu, sinus infections
DRUGS - NSAIDs, quinolones, sulfa drugs, Tylenol, naphthalene, artificial food coloring
FOOD - fava beans and other legumes, sulfites, menthol-containing foods (toothpaste, mouthwash)

20

Acute oxidative damage from Glucose-6-phosphate dehydrogenase deficiency can lead to hemolytic anemia which presents with?

paleness
jaundice
dark urine
fatigue
shortness of breath/rapid heart rate
splenomegaly

21

What treatments are available for Glucose-6-phosphate dehydrogenase deficiency?

dietary restriction
drug restriction

22

Galactosemia is due to a deficiency is what enzyme?

galactose-1-phosphate uridyl transferase
(involved with breakdown of dietary sugar galactose)

23

What are the symptoms of galactosemia?

newborns present with vomiting, lethargy, failure to thrive, and jaundice within 2 weeks

24

If untreated, galactosemia can lead to what?

mental retardation
cataracts
liver cirrhosis

25

What treatments are available for galactosemia?

feed formulas lacking in milk sugars (galactose and lactose)

26

Hereditary Fructose Intolerance results from deficiency in what enzyme?

fructose-1-phosphate aldolase (involved in breakdown of dietary fructose)

27

When does Hereditary Fructose Intolerance present and what are the symptoms?

presentation age varies (depends on when foods with fructose are introduced)
Symptoms: minimal to severe
Severe: failure to thrive, vomiting, jaundice and seizures

28

How would you treat Hereditary Fructose Intolerance?

fructose food restriction

29

List the 4 glycogen storage diseases affecting the liver.

Von Gierke (breakdown)
Cori (breakdown)
Anderson (synthesis)
Hepatic phosphorylase deficiency (breakdown)

30

Which enzyme is deficient in Von Gierke?

glucose-6-phosphate

31

Which enzyme is deficient in Cori disease?

amylo-1,6-glucosidase (debrancher enzyme)

32

Which enzyme is deficient in Anderson disease?

glycogen brancher enzyme (synthesis of glycogen)
4,6 transferase

33

What is the inheritance pattern for hepatic phosphorylase deficiency?

autosomal
x-linked

34

How does Von Gierke present?

hepatomegaly
hypoglycemia

infants-sweating, fast HR

35

How does Cori disease present?

hepatomegaly
muscle weakness

36

How does Anderson present?

hypotonia
abnormal liver function w/i first year >>>liver failure

37

How does hepatic phosphorylase deficiency present?

hepatomegaly
hypoglycemia
failure to thrive

38

How would you treat Von Gierke disease?

frequent feeding to reduce hypoglycemia
avoid fasting

39

How would you treat Cori disease?

frequent feeding to reduce hypoglycemia

40

How would you treat hepatic phosphorylase deficiency?

carbohydrate supplementation

41

List 2 glycogen storage diseases affecting muscle.

Pompe
McArdle

42

Which enzyme is deficient in Pompe?

a-1,4-glucosidase (necessary for glycogen breakdown)

43

Which enzyme is deficient for McArdle?

muscle phosphorylase (necessary for breakdown of muscle glycogen during exercise)

44

How does Pompe present?

in infancy with hypotonia, delay in gross motor milestones

enlarged heart
cardiac failure within 2 years

45

What treatment is available for Pompe?

no current treatment
-experimenting with enzyme replacement therapies

46

How does McArdle present?

presents in ADOLESCENSE with muscle cramps during exercise

47

What treatment is available for McArdle?

no current treatment

48

List 2 steroid metabolism disorders.

Congenital Adrenal Hyperplasia (CAH)
Androgen Insensitivity Syndrome

49

What is the most common cause of ambiguous genitalia in female newborns?

Congenital Adrenal Hyperplasia (CAH)

50

In 90% of cases Congenital Adrenal Hyperplasia (CAH) is due to what enzyme deficiency?

21-Hydroxylase

51

25% of Congenital Adrenal Hyperplasia (CAH) cases have the salt-losing form. How does it present?

2-3 weeks of life with circulatory collapse
- hypernatremia
- hyperkalemia

52

What is the inheritance pattern of Congenital Adrenal Hyperplasia (CAH)?

autosomal
- seen in males
-ambiguous genitalia in females

53

Affected females are virilized due to accumulation of ?

adrenocorticosteroids (many have testosterone-like functions)

54

How are Congenital Adrenal Hyperplasia (CAH) infants treated?

replacement cortisol for life (with increases given during times of stress)

**fludrocortisone is given as well in salt-losing forms

*plastic surgery for females

55

Androgen insensitivity syndrome is due to defect in what?

defective testosterone receptor
(normal levels of testosterone are produced but due to lack of receptors genes cannot be expressed)

56

When is Androgen insensitivity syndrome identified?

not identified until lack of menses

in cases of "inguinal" hernia which is actually internalized testes

57

What is the inheritance pattern of Androgen insensitivity syndrome ?

x-linked recessive
46 XY

58

List a lipid metabolism disorder.

Familial Hypercholesterolemia

59

What is the inheritance pattern for Familial Hypercholesterolemia?

autosomal dominant single-gene
**associated with high morbidity and mortality

60

How can Familial Hypercholesterolemia present in childhood?

xanthomata - buildup of cholesterol under the skin

61

How would you treat Familial Hypercholesterolemia?

dietary restriction
statin drugs (HMG-CoA reductase inhibitors)

62

What is the result of the mutation in Familial Hypercholesterolemia?

problems with the LDL receptor

63

What are the 4 main classes of problems with the receptor?

1. Reduced/defective biosynthesis
2. Reduced/defective transport
3. Abnormal binding of LDL by the receptor
4. Abnormal internalization of the receptor

64

What are the two lysosomal storage disorders?

Mucopolysaccharidosis
Sphingolipidosis

65

What is the most common Mucopolysaccharidosis?

Sanfilippo syndrome

66

How does Sanfilippo Syndrome (Mucopolysaccharidosis) present?

2nd year of life - coarsening of features, skeletal changed, progressive intellectual loss, seizures and death in early adult life

67

What enzyme is deficient in Mucopolysaccharidosis?

any one of four enzymes involved in degradation of heparin sulfate

68

What is the treatment for Mucopolysaccharidosis?

no standard treatment

69

What are the two most common Sphingolipidosis disorders?

Tay-Sachs
Gaucher

70

How is Sphingolipidosis characterized?

inability to degrade sphingolipids

71

What is the result of inability to degrade spingolipids?

accumulation of lipids or glycolipids, especially in brain, liver and spleen

72

If the CNS is involved in Sphingolipidosis, what is the progression of the disease?

mental deterioration
seizures
death in childhood

73

What enzyme is deficient in Tay Sachs?

B-hexosaminidase
(results in accumulation of sphingolipid GM, ganglioside)

74

What population has a high incidence of Tay-Sachs?

Ashkenazi Jews

75

How does Tay-Sachs present?

at 6 months with poor feeding, lethargy, eventual developmental regression and feeding difficulties

Death usually occurs by 3 due to respiratory infections

(less severe forms are reported)

76

How is diagnosis of Tay-Sachs aided?

cherry red spot in center of macula fundus

77

What is the treatment for Tay-Sachs?

no current treatment

78

What enzyme is deficient in Gaucher?

glucosylceramide B-glucosidase

79

What population has a high incidence of Gaucher?

Ashkenazi Jews

80

What is the most common Sphingolipidosis?

Gaucher

81

Describe Type 1 Gaucher.

adult onset (most common form)
pain in limbs, joints and/or trunk
tendency to bone fractures
hepatomegaly
mild anemia
some changes in vertebrae
CNS is spared

82

Describe Type 2 Gaucher.

presents between 3-6 months
CNS involvement
Failure to thrive
hepatosplenomegaly
developmental regression
neurological deterioration
**seizures
Death by age 2 due to repeated respiratory infections

83

Describe Type 3 Gaucher.

presents in childhood with intermediate symptoms

84

How would you treat Gaucher?

Type 1/3
analgesics for pain management
Splenectomy in some cases
Cerezyme (enzyme replacement therapies)

Type 2
no known treatment

85

List two nucleic acid disorders.

Lesch Nyhan Syndrome
Adenosine Deaminase Deficiency

86

What enzyme is deficient in Lesch Nyhan?

HGPRT (hypoxanthine guanine phosphoribosyltransferase)
- involved in salvage pathway of purine

87

What product builds up due to inability to salvage purines?

hypoxanthine
guanine
PRPP

**also causes a feed forward reaction to de novo synthesis

88

Increased levels of PRPP causes activation of what pathway?

de novo synthesis of purines
-levels can be 200x higher

89

Breakdown of excess purines will result in accumulation of ?

uric acid

90

What results from too much uric acid?

crystals form>>>gout

"sand in diaper"

91

What are the symptoms of Lesch Nyhan?

uncontrolled movements
spasticity
mental retardation
compulsive self-mutilation

92

What is the treatment for Lesch Nyhan?

Allopurinol, but does NOT seem to treat the neurological symptoms

93

What enzyme is responsible for 15% of all cases of SCID (Severe combined immunodeficiency syndrome)?

adenosine deaminase

94

How does adenosine deaminase deficiency present?

in infancy with recurrent bacterial and viral infections

**if untreated can lead to death

95

What is adenosine deaminase responsible for converting?

AMP to IMP in the purine salvage pathway

96

What immune deficiencies are seen in patients with adenosine deaminase deficiency?

deficient in T and B cells leaving them without a functional immune system

97

What is the treatment for adenosine deaminase deficiency?

no current treatment

clinical trials under way using gene therapy to treat SCID

98

What is a porphyrin?

ringed structures that can chelate metal

99

List two Porphyrin Metabolism Disorders?

Acute Intermittent Porphyria
Congenital Erythropoietic Porphyria

100

What enzyme is deficient in Acute Intermittent Prophyria?

uroporphyrinogen I synthase
-used in bone marrow heme synthesis
-leads to increased excretion of the precursors porphobilinogen and delta-aminolevulinc acid in urine

101

What are the symptoms of Acute Intermittent Prophyria?

abdominal pain
weakness
vomiting
mental and emotional disturbances
anemia
some:
hallucinations
coma

102

What can precipitate Acute Intermittent Prophyria?

use of certain drugs
steroids
anticonvulsants
barbituates

103

What enzyme is deficient in Congenital Erythropoietic Porphyria?

uroporphyrinogen III synthase
- in bone marrow heme synthesis

104

What are the symptoms of Congenital Erythropoietic Porphyria?

-extreme photosensitivity
-hemolytic anemia - require blood transfusions and splenectomy
-red/brown discoloration of teeth, fluoresce red under UV light

105

6 month old is brought in for recurrent respiratory infection. The child seems to be moving backwards developmentally and has a history of seizures. Testing reveals a deficiency in _______ , leading to a diagnosis of _____.

glucosylceramide b-glucodidase
Gaucher