Lysosomal storage disease

Question 1

What is defective and what accumulates in MPS1 and MP2 (Hurler and Hunter)

what are the clinical presentation.

Answer 1

Hurler: lack L-iduronidase

accumulates: dermatin sulfate and heparin sulfate
- (has gradations with hurler/hurler-scheie/scheie)
- *hepatosplenomegaly
- coarse skin
- corneal clouding
- autosomal recessive

Hunter: lack iduronate sulfatase
Accumulates: dermatin sulfate and heparin sulfate
-coarse skin
SPECIAL: X linked recessive, one of two (Fabry is other one)
No corneal clouding.

Question 2

What are the major roles of these ?

Glycerophospholipids

Sphingolipids

Glycolipids

Answer 2

Glycerophospholipid: membrane structure, signaling, detergents
-made in SER > important component of surfactant which keeps alveoli open, premature neonates can’t produce enough phospholipids > respiratory distress hormone

Sphingolipids: sphingomyelin major conductor of signals in nervous system

*sphingosine + acyl coA > ceramide
Ceramide + Phosphocholine > sphingomyelin

Glycolipids: also have a major role in CNS
-primary glycolipid in animals is glucosphingolipids

• Ceramide + glucose > glucocerebroside
• Ceramide + galactose > galactocerebroside
• Ceramide + galactose, glucose, or 2 or more hexose or hexose amine > globoside. (ex. trihexosylceramide) - storage product in Fabry.

Gangliosides: ceramide oligosaccharide with at least on SIALIC acid. (converted from globosides)

Question 3

What accumulates in Gaucher, defective enzyme, the presentation.

Answer 3

Lipid accumulating: glucocerebroside

Enzyme: beta-glucocerebrosidase

Symptoms:
enlarged liver and spleen, bone necrosis, mental retardation
*tissue paper macrophages

Oh my Gauch that Gucci bro.

Question 4

What is Krabbe’s disease?

Answer 4

Accumulating: galactocerebroside

Enzyme: BETA-Galactosidase

myelin almost absent, neurologic degeneration,

The alaskan krabb is out of this world.

Question 5

What is Niemann Pick disease?

Answer 5

Accumulating: sphingomyelin

Enzyme: sphingomyelinase

• Hepatomegaly, mental retardation, cherry red macula
• foamy cell

pick big nose with sphinger.

Question 6

What is Fabry disease

Answer 6

We fabricated a galaxy out of ceramics

Accumulating: the globoside: trihexosylceramide aka ceramide trihexoside
Angiokeratoma: the rash on the chest

Enzyme: ALPHA: galactosidase

Pain in extremeties, ocular abnormalities, CV disease, renal failure.

Question 7

Tay Sach’s disease

Answer 7

Accumulating: GM2 gangliosides

Enzyme: hexosaminidase A

neurologic disorder, cherry red macula, NO hepatosplenomegaly

gang of six small jews

Question 8

What is going on in metachromatic leukodystrophY?

Answer 8

Accumulating: cerebroside sulfate aka sulfatide

Enzyme: aylsulfatase A

demyelination of CNS and PNS resulting in ataxia and dementia.

hey bro, Me look yellow like sulfur.

Question 9

Pompe diseas?

Answer 9

Deficiency: lysosomal alpha 1,4 glucosidase

Yo gook, id like one mandu be4 dinner

Accumulation of glycogen in liver, heart and muscle, cardiomegaly

Question 10

What enzyme besides phenylalanine hydroxylase can be mutated and lead to PKU

Answer 10

An important cofactor in the conversion of phenylalanine to tyrosine is tetrahydrobiopterin.

Tetrahydrobiopterin is made from dihydrobiopterin via dihydropteridine reductase.

Lack of phenyalanine to tyrosine results in PKU, catecholamine synthesis is fked up altho tyrosine in diet is sufficient.