Final Exam Pathologies

Question 1

Respiratory Distress Syndrome (RDS) -(Dipalmitoyl Phosphatidylcholine (DPPC) or Dipalimotyl Lecithin (DPL)) deficiency

Answer 1

• Associated with insufficient surfactant production in lungs in preterm infants, can give mother steroids in advance to hasten fetus surfactant production
• Can occur in adults due to damage/destruction of surfactant producing pneumocytes

Question 2

Paroxysmal Nocturnal Hemoglobinura -PGAP2 protein deficiency

Answer 2

• PGAP2 assists in attaching GPI to membrane proteins in hematopoietic cells
• PGAP2 deficiency → Absence of GPI on membrane → Complement induced destruction of RBCs
• Hemolytic anemia
• Raised reticulocytes
• Red urine
• Can lead to thrombosis

Question 3

Mabry Syndrome/Hyperphosphatasia with Mental Retardation Syndrome -GPI Mannosyltransferase 2 deficiency

Answer 3

• GPI Mannosyltransferase 2 is involved with GPI synthesis
• Severe mental retardation
• Elevated alkaline phosphatase serum
• Hypoplastic terminal phalanges
• Distinct facial features: hypertelorism, broad nasal bridge, rectangular face

Question 4

Niemann-Pick Disease -Sphingomyelinase deficiency

Answer 4

-Accumulation of sphingomyelin
-Severe infantile form (A): -deposits in liver/brain → neurodegeneration -hepatosplenomegaly filled with lipid - severe mental retardation -death in early childhood
-Less severe form (B): - deposits in liver, spleen, lungs, bone marrow -death in early adulthood
Dx: -Enzyme activity measurement/DNA analysis -Histological tissue examination: -Foamy cells
Tx: -Recombinant enzyme replacement therapy

Question 5

Fabry Disease -a-Galactosidase deficiency

Answer 5

-Accumulation of globosides in vascular endothelilal lysosomes of brain, heart, kidney, skin
-Acroparasthesias (episodic pain in hands/feet)
-Angiokeratomas (clusters of small dark red spots on skin)
-Hypohidrosis
-Corneal opacity
-Tinnitus/hearing loss
-Progressive kidney damage/stroke/heart attack
-Burning pain in lower extremities
Dx: -Enzyme activity measurement/DNA analysis -Histological tissue examination
Tx: -Recombinant enzyme replacement therapy

Question 6

Tay-Sachs Disease -B-Hexosaminnidase A deficiency

Answer 6

-Accumulation of gangliosides (GM2)
-Rapid/progressive neurodegeneration
-Blindness
-Cherry-red macula
-Muscular weakness
-Seizures
Dx: -Enzyme activity measurement/DNA analysis -Histological tissue examination: shell-line inclusion bodies
Tx: -Recombinant enzyme replacement therapy

Question 7

Gaucher -B-Glucosidase deficiency

Answer 7

-Accumulation of gluocerebrosides in macrophages
-Hepatosplenomegaly
-Osteoporosis of long bones
-CNS involvement in rare juvenile/infantile forms
Dx: -Enzyme activity measurement/DNA analysis -Histological tissue examination: wrinkled tissue paper appearance of cytosol
Tx: -Recombinant enzyme replacement therapy -Bone marrow transplantation

Question 8

CPT-I Deficiency

Answer 8

-Affects the liver’s ability to synthesize glucose during fast
-Severe hypoglycemia, coma, and death
Tx: avoid prolonged fast, low LCFA and high carbohydrate diet, supplemented with MCFA and, if necessary, carnitine supplementation

Question 9

CPT-II Deficiency

Answer 9

-Decreased ability of Cardiac and skeletal muscle to use LCFA as fuel during fast
-Cardiomyopathy, muscle weakness + myoglobinemia following prolonged exercise
Tx: avoid prolonged fast, low LCFA and high carbohydrate diet, supplemented with MCFA and, if necessary, carnitine supplementation

Question 10

Carnitine Deficiency

Answer 10

-Decreased ability of tissues to use LCFA as fuel during fast
-Due to liver disease, malnutrition, strictly vegetarian diet or hemodialysis, which removes carnitine from the blood, Increased requirement in carnitine during pregnancy, severe infection, or trauma
Tx: avoid prolonged fast, low LCFA and high carbohydrate diet, supplemented with MCFA and, if necessary, carnitine supplementation

Question 11

MCAD Deficiency

Answer 11

-Medium-chain fatty acyl-CoA dehydrogenase deficiency
-Decrease in FA oxidation → severe hypoglycemia
-Infants are particularly affected by MCAD deficiency because breast milk contains primarily MCFAs.
Tx: high-carbohydrate diet

Question 12

Zellweger Syndrome -Proteins peroxins deficiency

Answer 12

• Peroxins required for assembly of peroxisomes, peroxisomes shorted VLCFAs
• Peroxin deficiency → lack of peroxisomes → accumulation of VLCFA in different tissues.
• Can result in deficiency of plasmalogens – important for brain and lung function

Question 13

Adrenoleukodystrophy (ALD) -Transporter that transport VLCFA into peroxisome for degradation deficiency

Answer 13

• Accumulation of VLCFA in blood and tissues.
• High level of VLCFAs can stimulate inflammation that severely affects myelin in CNS, adrenal complex and Leydig cells in the testes.
• Hyperactivity and disruptive behavior

Question 14

Smith-Lemli-Opitz Syndrome (SLOS) -3β-hydroxysterol ∆7-reductase deficiency

Answer 14

-Error of cholesterol synthesis
-Severe variant ( type II SLOS): Infants often die from multiple congenital abnormalities.
-Mild form: minor physical abnormality, coupled with behavioral problems including autism and self-injurious behavior.
-Older children and adults with SLOS frequently have clinical depression and aggression.
Tx: Dietary cholesterol supplementation may also help prevent the development of autistic behavior in SLOS

Question 15

21a-Hydroxylase Deficiency

Answer 15

• Steroid hormone synthesis disease
• Mineralcorticoids and glucocorticoids are virtually absent
• Over production of androgens → masculinization in females, over virulization in males

Question 16

Cholelthiasis (gallstones)

Answer 16

-Bile salt deficiency → cholesterol w/out bile salts