Lysosomal Storage Disorders Flashcards
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
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
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
Gaucher Inheritance/Gene info
- Gene: GBA
- Chromosome 1
- Autosomal recessive inheritance
- Malfunctioning enzyme is glucocerebrosidase
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
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
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
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
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
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
Pompe Inheritance/Gene info
- Gene: GAA
- Chromosome 17
- Autosomal recessive inheritance
- Enzyme deficiency is acid alpha glucosidase
- Glycogen buildup
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
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
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
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
MPS Type III
- Autosomal recessive inheritance
- Milder skeletal phenotypes
- Still coarse facial features
- No associated cardiac problems
- Progressive sleep and behavioral difficulties
MPS Type IV
- Autosomal recessive inheritance
- Severe skeletal phenotypes
- Chest deformities
- Heart problems
- Short stature
- Malformed bones
- Macrocephaly
- Normal cognitive function
MPS Type VI
- Autosomal recessive inheritance
- Coarse facial features
- Short stature
- Corneal clouding
- Cardiac problems
- Normal cognitive function
MPS Type VII
- Autosomal recessive inheritance
- Developmental delay
- Regression
- Course facial features
- Hepatosplenomegaly
- Recurrent ENT problems
- Cardiac problems
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)
MPS Type III-VII treatments
-Enzyme replacement therapy