07b: Lysosomal Storage Diseases Flashcards
LSDs result from (excess/deficiency) in (X) enzymes, resulting in:
Deficiency;
X = lysosomal
Accumulation of insoluble/inert substances or metabolites within lysosome
Most lysosomal storage disorders are inherited in (X) fashion. List key exception.
X = autosomal recessive
Hunter’s (X-linked recessive)
Most lysosomal storage disorders are seen in (young/old) patient population.
Young (infants and small children)
LSDs: typically involve enlargement of which organ(s)?
Liver and spleen (hepatosplenomegaly) (and lymph nodes)
Heterophagy differs from autophagy in which key way?
Heterophay is breakdown of exogenous macromolecules; autophagy is turnover of intracellular organelles (endogenous)
T/F: Neuronal damage is frequently associated with lysosomal storage diseases.
True
LSDs: distribution of stored material (organs) is determined by which two factors?
- Site where most material is found (gangliosides in brain)
2. Location of most degradation (RES/macrophages in nodes, spleen, liver)
List the 3 major categories of macromolecules that accumulate in LSDs.
- Sphingolipids
- Mucopolysaccharides (proteoglycans)
- Glycogen
Sphingolipids are particularly abundant in which tissue type?
Brain and nervous tissue membranes
Tay Sach’s Disease: missing enzyme is (X) and accumulated material is (Y).
X = hexosaminidase Y = gangliosides
Tay Sach’s Disease: (X) is major tissue affected. List some of the clinical manifestations.
X = neural and retina
Motor/mental deterioration, blindness, hypotonia (muscle flaccidity)
“Cherry red spot” is clinical manifestation of which types of diseases?
Lysosomal storage diseases
Tay Sachs: EM of lysosomes will appear like…
Whorled inclusions (layers of membrane); look like onion
Niemann-Pick Disease: missing enzyme is (X) and accumulated material is (Y).
X = sphingomyelinase Y = sphingomyelin (and cholesterol)
Niemann-Pick Disease: Type A variant is (X)% of cases. What makes it different from Type B?
X = 75-80
- CNS involvement
- Progressive wasting and EARLY death (by age 3)
Adult patient with liver enlargement and spleen enlargement to 10x normal size. Which LSD(s) could this be?
- Niemann-Pick Disease (Type B)
2. Gaucher’s Type I
EM of nerve cells with concentric “myelin” figures (Zebra bodies) indicative of which LSD(s)?
- Niemann-Pick Disease
2. Hurlers Syndrome
Gaucher Disease: missing enzyme is (X) and accumulated material is (Y).
X = Glucocerebrosidase Y = Glucocerebrosides
Gaucher Disease: Type 1 is (X)% of cases. How does it differ from Type 2?
X = 80 (“classic” type)
Non-neurotropic, adult type, only slightly decreased longevity
Erlenmeyer flask deformity seen in which LSD?
Gaucher’s
Gaucher’s disease: (low/high) platelet count, (low/high) WBCs, and (low/high) RBCs.
All low - sequestration; bone marrow replaced by Gaucher cells
Mucopolysaccharidosis (MPS) I is also called (X) and the missing enzyme is (Y).
X = Hurlers Syndrome Y = alpha-L-iduronidase
Hurlers Syndrome: what’s the accumulated material?
Haparan and Dermatan sulfate
Hurlers Syndrome: (X) is an important cause of death.
X = MI
Which LSD has clinical manifestations that include cardiac valvular lesions, coronary artery deposits, and brain lesions?
Hurlers (and all MPS)
T/F: Glycogenoses is deficiency of ANY enzyme involved in glycogen metabolism.
True
Hepatic form of glycogenoses is (X) disease with (Y) missing enzyme.
X = Von Gierke's Y = glucose-6-phosphatase
Von Gierke’s disease: which two symptoms dominate the clinical picture?
Hepatomegaly and hypoglycemia
Pompe’s disease with (X) missing enzyme and (Y) accumulated material.
X = alpha-glucosidase (acid maltase) Y = glycogen
Pompe’s disease: which main symptom dominates the clinical picture?
Cardiomegaly (but muscle weakness and neuro symptoms also involved)
