glycolipid disorders Flashcards
What are lysosomes
Garbage centers in cells that are acidic, contain about 50 hydrolase enzymes that break down macromolecules into smaller components
How are hydrolases targeted to the lysosome
Mannose-6-phosphate on surface of hydrolases bind to M6P receptors
what is a lysosomal storage disease
Occurs when lysosomal enzyme is missing/deficient resulting in substrate accumulation in various organs
Signs of LSD in brain vs other organs
brain: neurodegeneration. Other organs: increase in mass
Inheritance pattern of MOST lysosomal storage diseases
autosomal recessive
List the X-linked lysosomal storage diseases
- Fabry disease (alpha-galactosidase). 2. Hunter syndrome (iduronate-2-sulfatase). 3. Danon disease (lysosomal associated membrane protein 2)
What is the main problem in lysosomal storage diseases
Gradual accumulation that slowly leads to storage and dysfunction. The accumulating substrate is usually not toxic
time course of lysosomal storage diseases
Progressive disease that present less acutely than many other metabolic conditions
Symptoms of LSD in brain
macrocephaly, cognitive regression, seizures, ataxia
Symptoms of LSD in eyes
corneal clouding, cherry red spot in retina (Tay Sachs)
Symptoms of LSD in ear/nose/throat
macroglossia, sleep apnea
Symptoms of LSD in liver
hepatosplenomegaly- can be massive, with protuberant belly. Typically does not lead to LFT abnormalities
Symptoms of LSD in kidneys
Progressive renal failure and proteinuria (Fabry disease)
Symptoms of LSD in skeletal system
dysostosis multiplex (vertebral breaking, abnormal bony structure on x ray), joint stiffness, short stature
Symptoms of LSD in skin
coarseness/thickening
Gaucher type 1 presentation
Adult onset and increased incidence in Ashkenazi jews- fatigue, bone pain, hepatosplenomegaly
Gaucher type 1 labs/ histology
anmia, thrombocytopenia, gaucher cells (macrophages) in bone marrow
gaucher type 1 imaging
avascular necrosis in bones, erlenmeye flask deformity (x ray of distal femur)
Gaucher type 1 enzyme deficiency and treatment
Beta glucosidase (aka glucocerebrosidase) deficiency results in build up of glucosylceramides. Treated with imiglucerase, but pts will not die from this dz usually even if untreated
Tay Sachs type 1 presentation
infantile or early childhood. Increased in Ashkenzi jews. Blindness, seizures, increased startle reflex, mental/motor deterioration.
Tay Sachs type 1 exam/ histology
Cherry red spot in eye Lipid loaded cells
Tay Sachs enzyme deficiency and treatment
Beta-hexosaminidase A deficiency. Treatment is supprtive and pts will likely die
Fabry disease presentation
Pre-teen/teen w/ acroparathesias or in adult with renal failure/ angiokeratomas or older adult with left ventricular hypertrophy or stroke.
Fabry disease clinical sx
acroparesthesia (pain in palms/soles, especially with fevers), dark red angiokeratomas in bathing suit distribution, LVH/stroke, proteinuria and renal failure
family history in Fabry disease
renal failure in males
Fabry disease enzyme deficiency and treatment
Alpha-galactosidase. Treated with agalsidase beta
Pompe disease presentation
Infantile: present at 3-6 months; dead at 1 year (w/o Rx). Childhood: not likely tested on. Adult: slowly progressive muscle weakness
Pompe disease clinical sx
Infant with progressive muscle weakness (floppy) and LVH. Adult with proximal muscle weakness and respiratory weakness (sleep apnea)
Pompe disease labs/imaging
Elevated CK; glycogen on muscle biopsy
Pompe disease enzyme deficiency and treatment
alpha-glucosidase deficiency resulting in elevated glycogen. Treated with alglucosidase alfa
Hunter disease presentation
childhood- coarse facies, airway dz, ear infection, NO corneal clouding, hearing loss
Hunter disease enzyme deficiency and treatment
iduronate sulfatase. Treatment: idursulfase
Hurler syndrome presentation
childhood- coarse facies, airway dz, ear infections, corneal clouding, hearing loss
Hurler syndrome enzyme deficiency and treatment
alpha iduronidase. Treatment: iaronidase
mucopolysaccharidoses are caused by
defects in degradation of proteoglycans
McArdle disease presentation
adults- muscle weakness and cramping, often exercise related cramping and myogolbuinuria (coffee colred urine after exercise)
McArdle disease labs
high CK
McArdle disease enzyme deficiency and treatment
glycogen phosphorylase- treated with support
