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Flashcards in Enzyme Deficiencies Deck (71):
0

groups of inborn errors of metabolism

1. metabolites
2. metabolic pathway
3. Function of enzyme
4. function of organelle

1

Most IEMs, genetics wise are ...

autosomal recessive or X linked recessive

2

IEMs of amino acid metabolism

PKU
Oculocutaneous albinism
branched chain aa metabolism - maple syrup urine disease

3

IEMs of Carbohydrate metabolism

G6PDD
monosaccharide metabolism - galactosemia, hereditary fructose intolerance
glycogen storage disorders - von gierke, cori, anderson, pompe, Mcardle syndromes; hepatic phosphorylase deficiency

4

IEMs of steroid metabolism

congenital adrenal hyperplasia
androgen insensitivity syndrome

5

IEM of Lipid metabolism

familial hypercholesterolemia

6

Lysosomal storage disorders

mucopolysaccharidoses
sphingolipidoses

7

Purine/pyrimidine metabolism

Lesch Nyhan syndrome
SCID

8

IEM of Porphyrin metabolism

Hepatic
Erythropoietic

10

Untreated PKU (phenylketonuria) leads to

severe intellectual impairments and development of seizures

10

Defects in branched chain AA metabolism leads to

Maple syrup urine disease

11

What deficiency causes PKU?

defect in the enzyme Phenylalanine hydroxylase (PAH) which converts Phenylalanine into Tyrosine, results in deficiency of Tyrosine which is required for melanin synthesis
this leads to buildup of phenylalanine which then converts to phenylpyruvic acid that is excreted through urine

12

Branched chain AA?

Valine
Leucine
Isoleucine

13

What is the prognosis for pts with Maple syrup disease?

tend to be susceptible to deterioration even with dietary restriction
tend to suffer recurrent illnesses from the catabolic protein breakdown

14

What defect leads to Maple syrup disease?

branched chain ketoacid decarboxylase deficiency leads to Val, Leu and Ile

15

Single largest metabolic disorder?

Glucose 6 Phosphate dehydrogenase

16

G6PDD genetically is ....

X linked recessive

17

What is G6PD responsible for?

oxidative step of pentose phosphate pathway

18

What type of cell in G6PDD pts is most affected?

Red blood cells because unlike other cells doesnt have other ways to handle oxidative stress

19

with G6PDD, there is a defect in ....

the ability to handle oxidative damage because there is reduced ability to produce NADPH, this is a potent reducer to protect against oxidative damage

20

G6PDD Pt suffers acute oxidative damage from exposure to moth balls, what could occur?

Hemolytic anemia - presents as jaundice (see in newborns with G6PDD), paleness, dark urine, fatigue, shortness of breath/rapid heart rate, splenomegaly

21

Galactosemia pts are deficient in ...

galactose 1-phosphate uridyl transferase

22

Galactosemic newborn presents with

vomiting, lethargy, failure to thrive and jaundice within the second week of life

23

Untreated galactosemia leads to

mental retardation
cataracts
liver cirrhosis

24

Hereditary Fructose intolerance is caused by?

deficiency in fructose-1-phosphate aldolase (Aldolase B)
leads to build up of Fructose in liver

25

Glycogen stores are largest in

liver and muscles

26

Congenital Adrenal Hyperplasia caused by

deficiency in 21-hydroxylase -90%
MCC of ambiguous genitalia in FEMALE newborns
salt losing form - presents 2-3 wks of life with circulatory collapse, hyponatremia, hyperkalemia

27

Androgen insensitivity syndrome

Receptor defective leaving pt unresponsive to testosterone leading to external female characteristics

28

Familial Hypercholesterolemia

Autosomal dominant single gene disorder
High morbidity and mortality rates via premature coronary artery disease

29

Familial Hypercholesterolemia is characterized by

problems with the LDL receptor which leads to increased endogenous synthesis of cholesterol

30

What issues can there be with receptors in FH?

reduced/defective biosynthesis
reduced/defective transport
abnormal binding of LDL by the receptor
abnormal internalization of the receptor

31

Mucopolysaccharidoses are characterized by

skeletal, vascular or CNS along with coarsening of facial features

32

What is Mucopolysaccharidoses due to?

progressive accumulation of sulfated polysaccharides

33

Sanfilippo syndrome

Most common MPS
due to deficiency in any one of four enzymes involved in degradation of heparin sulfate

34

Most common Sphingolipidoses?

Tay Sachs - high incidence among Ashkenazi jews
Gaucher

35

Tay Sachs is due to...

deficiency in subunit of beta-hexosaminidase, this results in accumulation of sphingolipid GM2 ganglioside

36

What is a diagnostic clue for Tay Sachs?

presentation of characteristic cherry red spot in the center of the macula fundus

37

Gaucher is due to ....

glucosylceramide beta glucosidase

38

Lesch Nyhan syndrome

Hypoxanthine guanine phophoribosyltransferase (HGPRT)
leads to increased amounts of purines - see 200x higher levels - likely due to increased amounts of PRPP

39

Symptoms of Lesch Nyhan syndrome

uric acid crystals
uncontrolled movements
spasticity
mental retardation
compulsive self mutilation

40

Adenosine Deaminase Deficiency

inherited immunodeficiency
defect in adenosine deaminase - responsible for 15% of SCID - bubble boy disease

41

Adenosine deaminase is responsible for ...

conversion of AMP to IMP in purine salvage pathway
pts are severely deficient in both T and B cells, leaving them without functional immune system

42

Porphyrins are ...

ringed structures which can chelate metal ions

43

What are the two main phorphyrin functions?

liver - cytochromes in ETC and detox of substances
Erythrocytes - hemoglobin

44

Acute Intermittent Porphyria

due to deficiency uroporphyrinogen I synthase which leads to increased excretion of precursors porphobilinogen and S-aminolevulinic acid in urine

45

Congenital Erythropoietic Porphyria characterized by

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

46

Congenital Erythropoietic porphyria due to

deficiency in uroporphyrinogen III synthase
see build up of reticulocytes since body in need of RBCs

47

is there an effective treatment for PKU?

supplementation with PAH prove ineffective
infant and child pts with PKU keep to strict diet low in phenylalanine
after normal neural development can relax dietary restrictions

48

Oculocutaneous albinism results from . . . .

a deficiency of tyrosinase which converts Tyrosine to Melanin

49

Phenotype of Oculocutaneous albinism?

no melanin production leads to lack of pigment in hair, skin, iris, and ocular fundus of patients

50

What results from the lack of pigment seen in OCA?

leads to poor visual acuity, nystagmus (pendular eye movements) and underdevelopment of fovea

51

What characterizes OCA type 1?

mutation within tyrosinase gene on chromosome 11q
classic albinism - no measurable tyrosinase activity

52

What characterizes OCA type 2?

due to mutation in P gene (mouse homolog called pink eye) on chromosome 15q

53

Newborns with Maple syrup urine disease present with?

first week of life with vomiting, alternating tone
if left untreated, then leads to death within a few weeks
treatment involves dietary restriction of intake of V, I and L

54

What are some sources of oxidative damage?

infection - colds and flu
Drugs - NSAIDS, quinolones, sulfa drugs, tylenol, drugs metabolized through liver, naphtalene (moth balls) and artifical food coloring
Foods - fava beans and other legumes, sulfites, menthol-containing foods

55

Acute oxidative damage in pt with G6PDD can lead to ...

hemolytic anemia which presents with paleness, jaundice, dark urine, fatique, shortness of breath/rapid heart rate, splenomegaly

56

G6PDD is genetically ...

very diverse - more than 100 different mutations identified

57

symptoms of Hereditary fructose intolerance

presentation age varies depends on when foods with fructose are introduced into diet
minimal to severe - failure to thrive, vomiting, jaundice, seizures

58

Von Gierke disease

glucose 6 phosphatase

59

Cori disease

amylo-1,6 glucosidase ( debrancher enzyme)

60

Anderson disease

glycogen brancher enzyme (synthesis enzyme)
impairs ability to build storage

61

Hepatic phosphorylase deficiency

multimeric enzyme complex with subunits coded for by autosomal and X linked genes

62

How does Von Gierke disease present?

hepatomegaly (seen when glycogen stores cannot be broken down)
hypoglycemia in infants presents as sweating, fast heart rate

63

How does Cori disease present?

hepatomegaly
muscle weakness

64

How does Anderson disease present?

hypotonia, abnormal liver function within first year of life, progresses to liver failure quickly

65

How does Hepatic phosphorylase deficiency present?

hepatomegaly
hypoglycemia
failure to thrive

66

Which glycogen storage disease affects the liver and has no effective treatment?

Anderson disease

67

Pompe disease

glycogen storage disease that affects muscle
due to deficiency in lysosomal enzyme alpha 1,4 glucosidase which is necessary for glycogen breakdown

68

McArdle Disease

due to deficiency in muscle phosphorylase
necessary for breakdown of muscle glycogen during exercise

69

symptoms of Pompe disease

presents in infancy with hypotonia, delay in gross motor milestones, due to muscle weakness,
eventually leads to enlarged heart and death from cardiac failure within first 2 years
no current treatment

70

symptoms of McArdle

presents in adolescence with muscle cramps during exercise
no effective treatmetn