Glycolipid disorders Flashcards
Lysosomal storage diseases
when a lysosomal enzyme is deficient/missing –> substrate accumulation (storage) in various organs (you can’t get rid of the substrate)
not acutely toxic
LSD inheritance
majority = autosomal recessive
3 X-linked diseases: Fabry (alpha-galactosidase), Hunter syndrome (iduronate-2-sulfatase), Danon disease
LSD presentation
usually progressive diseases, with less acute presentation than other metabolic diseases
Brain LSD manifestations
macrocephaly, cog regression
Eye LSD manifestations
corneal clouding, cherry red spot (Tay Sachs or Niemann-Pick)
ENT LSD manifestations
macroglossia, sleep apnea
Liver LSD manifestations
hepatosplenomegaly c preserved hepatic function
Kidney LSD manifestations
progressive renal failure + proteinuria (Fabry disease)
Skeletal LSD manifestations
dysostosis multiplex, joint stiffness, short stature
What is dysostosis multiplex?
abnormal bony structure on X-rays; vertebral “beaking”, broad bases of metacarpals and phalanges, scoliosis
Adult-onset, hepatosplenomegaly, anemia, thrombocytopenia
“foamy macrophages” on microscopy
normal life span, no CNS involvement
Gaucher Type I: deficiency of beta glucosidase (enzyme replacement therapy)
Difference in Gaucher 1 and 2
type 2 = infantile, acute, deadly; CNS involvement
Infant with increased startle reflex, NO hepatosplenomegaly, cherry red spot
Tay Sachs 1: deficiency of beta-hexosaminidase A. Fatal
X-linked disease
children –> acroparasthesias
young adults: proteinuria, angiokeratomas (bathing trunk distribution)
normal IQ
Fabry disease: deficiency of alpha galactosidase (enzyme replacement therapy)
presents with supranuclear gaze palsy, cherry red spot, BIG hepatosplenomegaly
Niemann-Pick = deficiency of sphingomyelinase
Infant with profound weakness and HOCM or Adult with proximal muscle weakness and sleep apnea
Pompe disease = deficiency of alpha glucosidase (enzyme replacement therapy)
child with hoarse voice, frequent URIs, hepatosplenomegaly, some learning problems; NO corneal clouding
Hunter disease = iduronate sulfatase deficiency. (enzyme replacement therapy) X-linked recessive
child with coarse facies, hepatosplenomegaly, CORNEAL CLOUDING
Hurler disease = alpha iduronidase deficiency (enzyme replacement therapy)
Muscle cramping after exercise, myoglobinuria (coffee colored urine after exercise)
McArdle disease = glycogen phosphorylase deficiency
Skin LSD manifestations
coarseness
Classic Gaucher cell appearance on histology
“crumpled tissue paper” appearance of cytoplasm (due to elongated lysosomes filled with glucocerebroside)
