Lysosomal Storage Disorders Flashcards Preview

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Flashcards in Lysosomal Storage Disorders Deck (21):
1

Gaucher Type I

-Least severe
- hepatosplenomegaly (HSM)
- enlarged liver and spleen leads to anemia and thrombocytopenia
-Bone disease
-Pulmonary tension
-Little to no neurological symptoms, may have Parkinsonian features
-Normal lifespan

2

Gaucher Type II

-Most severe
-HSM
- enlarged liver and spleen leads to anemia and thrombocytopenia
-NO bone disease
-Severe neurological symptoms
- seizures, opsithotonic posturing
-Typical lifespan is no longer than 2 years

3

Gaucher Type III

-Moderate severity
-HSM
-enlarged liver and spleen leads to anemia and thrombocytopeia
-Bone disease
-Moderate neurological symptoms
- oculomotor apraxia (jarring eye movement, difficulty with peripheral vision), seizures
-Somewhat limited lifespan, can be extended with treatment

4

Gaucher Inheritance/Gene info

-Gene: GBA
-Chromosome 1
-Autosomal recessive inheritance
-Malfunctioning enzyme is glucocerebrosidase

5

Gaucher Screening and Treatment

-Enzyme and molecular testing
-Bone marrow biopsy will show enlarged "Gaucher cells"
-Treatment with enzyme replacement therapy: Cerezyme
-New small molecular inhibitor Cerdelga is sometimes used for treatment instead of ERT

6

Fabry Symptoms

-GI Distress-Corneal whorl (does not affect vision)
-Left ventricular hypertrophy
-Proteinurea
-Hypohydrosis
- lack of sweat
- can lead to easy overheating
-Acroparathesias:severe pain in hands and feet
-Gradual hearing loss
-Depression/Anxiety

7

Fabry Inheritance/Gene info

- Gene: GLA
- X Chromosome
-Can affect females due to skewed X-inactivation
-X-linked inheritance with affected females (pseudo-dominant)
-Malfunctioning enzyme is alpha galactosidase

8

Fabry testing and treatment

-Enzyme testing can be useful on males
-Enzyme testing is not helpful for females because the enzyme deficiency may be limited, or may not be detected in the blood
-Molecular testing
-Symptomatic treatment of pain, cardiac issues, and GI distress with appropriate medication
-Enzyme replacement therapy with Fabrazyme, Replegal

9

Pompe Disease Symptoms - Infantile Onset

-Cardiomegaly
-Cardiorespiratory failure
-Difficulty breathing
-Muscle weakness (floppy baby)
-Head lag, delayed motor skills
-Difficulty feeding, enlarged tongue, hepatomegaly (enlarged liver)
-Glycogen storage disease

10

Pompe Disease Symptoms - Late Onset

-Respiratory difficulty
-Diaphragmatic weakness
-Muscle weakness, difficulty walking (these symtpoms can appear to be a type of muscular dystrophy)
-Difficulty maintaining weight
-Difficulty swallowing
-Acid maltase difficiency

11

Pompe Inheritance/Gene info

-Gene: GAA
-Chromosome 17
-Autosomal recessive inheritance
-Enzyme deficiency is acid alpha glucosidase
-Glycogen buildup

12

Pompe testing and treatment

-Enzyme testing
-Western blot to test for presence of protein-Molecular testing
-Enzyme replacement therapy with myozyme for infants, lumizyme for adults

13

Mucopolysaccharidoses (MPS)

-Types I-VII with subtypes
-Leads to improper breakdown of GAGs (glycosaminoglycans), which affect to connective tissue development
-Can be detected through MPS urine screen, enzyme testing, and molecular testing-Regression is a key symptom in most MPS types
-Skin pebbling occurs due to substrate buildup

14

MPS Type I

-Hurler Syndrome
- Autosomal Recessive Inheritance
-Coarse facial features
-Hepatosplenomegaly
-Cardiac problems
-Hydrocephalus
-Developmental delay
-Corneal clouding (DOES affect eyesight)
-Recurrent ENT problems
-Hearing loss
-Regression

15

MPS Type II

-Hunter Syndrome
- X-linked Inheritance
-Coarse facial features
-Hepatosplenomegaly
-Hydrocephalus
-CLEAR CORNEAS
--Regression
-Developmental delays
-Hearing loss
-Recurrent ENT problems
-Cardiac problems
SAME AS TYPE I BESIDES BEING X-LINKED AND CLEAR CORNEAS

16

MPS Type III

-Autosomal recessive inheritance
-Milder skeletal phenotypes
-Still coarse facial features
-No associated cardiac problems
-Progressive sleep and behavioral difficulties

17

MPS Type IV

-Autosomal recessive inheritance
-Severe skeletal phenotypes
-Chest deformities
-Heart problems
-Short stature
-Malformed bones
-Macrocephaly
-Normal cognitive function

18

MPS Type VI

-Autosomal recessive inheritance
-Coarse facial features
-Short stature
-Corneal clouding
-Cardiac problems
-Normal cognitive function

19

MPS Type VII

-Autosomal recessive inheritance
-Developmental delay
-Regression
-Course facial features
-Hepatosplenomegaly
-Recurrent ENT problems
-Cardiac problems

20

MPS Type I and Type II treatments

-Enzyme replacement therapy (does not cross blood/brain barrier)
-Bone marrow or stem cell transplant before onset of cognitive delay (less efficient in Type II than in Type I)
-Intrathecal ERT is in trial (enzyme given through the spinal column to access the blood/brain barrier)

21

MPS Type III-VII treatments

-Enzyme replacement therapy