inborne errors of metabolism, lysosomal and glycogen storage disorders Flashcards Preview

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Flashcards in inborne errors of metabolism, lysosomal and glycogen storage disorders Deck (29):
1

what causes alkaptonuria?

defect in homogentisic acid deoxygenase

2

alkaptonuria represents a problem with metabolising what AA?

impaired tyrosine and phenylalanine metabolism

3

how can alkaptonuria be diagnosed?

high homogentisic acid in urine

4

what is a late complication of undiagnosed maply sugar uine disease?

cerebral edema

5

what disease is associated with deficient acid alpha-clucosidase?

pompe disease

6

what enzyme defect causes:

normal glucose levels
severe cardiomegaly
glycogen accumulation in lysosomes

acid alpha-glucosidase

pompe disease

aka α-1,4-glucosidase and acid maltase

7

deffect in debranching enzymes alpha 1-4 transferase or alpha1-6 glucosidase leads to what symptoms? What is a key feature of the abnormal enzyme product?

hepatomegaly
keototic hypoglycemia
hypotonia & weakness

**abnormal glycogen with very short outer chains**

Cori disease (cori can't cut anderson can't add)

AB-CD
anderson-branching defect- cori debranching defect

8

what enzyme is defective in mcardle disease?

muscle glycogen phsphorylase

9

what step in glycogen processing is defective in mcardle disease?

muscle glycogen phsphorylase degreades glycogen into glucose-1-phosphate which can then be used for energy in muscle

sometimes referred to as myophosphrylase

10

what disease? what defect?

hepatomegaly and steatosis
fasting hypoglycemia
lactic acidosis
hyperuricemia
hyperlipidemia

von gierke disease

glucose 6 phosphatase

11

deficiency in what enzyme causes lactic acidosis, neurologic dysfunction and early death?

pyruvate dehydrogenase

12

Sphingomyelinase deficiency is found in what disease?

Niemann-Pick disease

13


peripheral neuropathy
- especially in hands and feet
angiokeratomas (small purple blemishes on skin)
cardiovascular disease
renal disease

α-galactosidase A deficiency

Fabry's disease

ceramide trihexose accumulates

14


hepatosplenomegaly
anemia
cherry red spots on macula
death

Niemann-Pick disease - Sphingomyelinase deficiency

sphingomyelin accumulates
histiocytes look "foamy"

15


hyperactive reflexes
optic atrophy
developmental delay

β-galactocerebrosidase deficiency - Krabbe's disease
galactocerebroside accumulates

16

hepatosplenomegaly
aseptic necrosis of heads of long bones
mild anemia
possible to live a normal lifespan

if CNS involved
death

β-glucocerebrosidase deficiency - Gaucher's disease

glucocerebroside accumulates in lysosomes of phagocytic cells

histiocytes (dendritic cells) look like wrinkled tissue paper

called Gaucher's cells

17


CNS degeneration
blindness
cherry red spot on macula
startle reflex
death

Hexosaminidase A

deficient in Tay-Sachs disease
GM2 ganglioside accumulates
lysosomes with onion skin

18

demyelination in CNS and PNS
resulting in ataxia and dementia

Arylsulfatase A

deficient in metachromatic leukodystrophy
cerebroside sulfate accumulates

19


gargoyle-like facies
corneal clouding
progressive mental retardation

α-L-iduronidase deficiency - Hurler's syndrome
heparan sulfate and dermatan sulfate accumulates in heart and liver

20


gargoyle-like facies
progressive mental retardation
all of which are less severe than Hurler's syndome

aggressive behavior

Iduronate sulfatase deficiency - Hunter's syndrome
heparan sulfate and dermatan sulfate accumulates

corneal clouding absent

remember: hunter's are aggressive

21



skeletal abnormalities
restricted joint movement
psychomotor retardation
early death
coarse facial features
high plasma levels of lysosomal enzymes

defect in N-acetylglucosamine-phosphotransferase causes - I-cell disease

Normally: proteins marked for localization to lysosomes are post-translationally modified in the Golgi mannose residues are phosphorylated by N-acetylglucosamine-phosphotransferase enzyme

without mannose-6-phosphate designation, the enzymes are secreted instead of being targeted to the lysosome

cells also cannot degrade endocytosed material becuase they can't be tagged due to enzyme deficiency

inclusion bodies build up intracellularly

Lysosomal enzymes are not activated extracellularly due to pH optimum for enzyme activation

22

what enzyme is deficiency in Hurler's disease? What builds up? What organs does it affect?

α-L-iduronidase
heparan sulfate and dermatan sulfate accumulates in heart and liver

23

What is deficient in metachromatic leukodystrophy? What accumulates?

Arylsulfatase A
cerebroside sulfate accumulates

24

What is deficient in Tay-Sachs disease? What accumulates? What is the appearance of lysosomes?

Hexosaminidase A

GM2 ganglioside accumulates
lysosomes with onion skin

25

What is deficient in Gaucher's disease? What accumulates? What is the appearance of the affected cells?

β-glucocerebrosidase

glucocerebroside accumulates in lysosomes of phagocytic cells

histiocytes (dendritic cells) look like wrinkled tissue paper

called Gaucher's cells

26

What is deficient in Niemann-Pick disease? What accumulates? What is the appearance of the affected cells?

Sphingomyelinase

sphingomyelin accumulates
histiocytes look "foamy"

27

what is the defect in I-cell disease?

N-acetylglucosamine-phosphotransferase

Normally: proteins marked for localization to lysosomes are post-translationally modified in the Golgi mannose residues are phosphorylated by N-acetylglucosamine-phosphotransferase enzyme

without mannose-6-phosphate designation, the enzymes are secreted instead of being targeted to the lysosome

cells also cannot degrade endocytosed material becuase they can't be tagged due to enzyme deficiency

inclusion bodies build up intracellularly

Lysosomal enzymes are not activated extracellularly due to pH optimum for enzyme activation

28

What is deficient in Krabbe's disease? What accumulates?

β-galactocerebrosidase deficiency -
galactocerebroside accumulates

29

What is deficient in von gierke disease? What are the clinical symptoms?

glucose 6 phosphatase

hepatomegaly and steatosis
fasting hypoglycemia
lactic acidosis
hyperuricemia
hyperlipidemia

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