Lysosomal Storage Disorders

Question 1

Gaucher Type I

Answer 1

• 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

Question 2

Gaucher Type II

Answer 2

• 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

Question 3

Gaucher Type III

Answer 3

• 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

Question 4

Gaucher Inheritance/Gene info

Answer 4

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

Question 5

Gaucher Screening and Treatment

Answer 5

• 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

Question 6

Fabry Symptoms

Answer 6

• 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

Question 7

Fabry Inheritance/Gene info

Answer 7

• 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

Question 8

Fabry testing and treatment

Answer 8

• 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

Question 9

Pompe Disease Symptoms - Infantile Onset

Answer 9

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

Question 10

Pompe Disease Symptoms - Late Onset

Answer 10

• 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

Question 11

Pompe Inheritance/Gene info

Answer 11

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

Question 12

Pompe testing and treatment

Answer 12

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

Question 13

Mucopolysaccharidoses (MPS)

Answer 13

• 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

Question 14

MPS Type I

Answer 14

• 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

Question 15

MPS Type II

Answer 15

-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

Question 16

MPS Type III

Answer 16

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

Question 17

MPS Type IV

Answer 17

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

Question 18

MPS Type VI

Answer 18

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

Question 19

MPS Type VII

Answer 19

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

Question 20

MPS Type I and Type II treatments

Answer 20

• 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)

Question 21

MPS Type III-VII treatments

Answer 21

-Enzyme replacement therapy