Glycolipid disorders

Question 1

Guacher type 1 (adult onset)

Answer 1

AR- common in ashkanazi jews
fatigue, bone pain, enlarging abdomen
anemia, thrombocytopenia, HSM, AVN in bones, EM flask deformity

Liver, spleen, bone marrow

enzyme- Beta glucosidase (glucocerebrosidase)

Tx- ERT- (recombinant glucocerebrosidase) imiglucerase, velaglucerase, taliglucerase
-oral substrate inhibition- eliglustat, miglustat

Question 2

what diseases are not AR

Answer 2

Fabry- XLD

Hunter XLR

Question 3

skin
skull
eyes
ENT
Liver
Kidneys
Skeletal

Answer 3

skin- coarseness

skull- macrocephaly, cognitive regression

eyes- corneal clouding, cherry red spot (tay sachs)

ENT- macroglossia, sleep apnea

Liver- HSM

Kidneys- proteinuria (fabry)

Skeletal- dysostosis multiplex, joint stiffness, short stature

Question 4

Tay Sachs disease

Answer 4

AR, more common in ashkanazi jews
progressive neurodegeneration, developmental delay,
-blindness, seizures mental and motor degeneration

manily CNS, will die

• cherry red spot on the macula*
• *increase startle reflex**
• *No HSM**

deficent enzyme- B-Hexosaminidase A,
accumulated substrate- GM2 Ganglioside

Question 5

Fabry

Answer 5

XR-

• Enzyme deficiency- Alpha galactosidase +Treatment*
• ceramide trihexoside is accumulated
• *Angiokeratomas (bathing trunk distribution), Renal Failure Acroparesthesias (pain in palms and soles (peripheral neuropathy of extremities)), Normal IQ**

Question 6

Pompe disease

Answer 6

AR
***enzyme deficiency- Alpha-glucosidase +Treatment: Infant with profound
weakness and hypertrophic CM or Adult with proximal muscle weakness and sleep apnea

Question 7

Hunter

Answer 7

XR
Enzyme deficiency- Iduronate sulfatase+Treatment
accumulation of heparan sulfate
mild hurler plus aggressive behavior

Coarse-appearing child, who is short, has hoarse voice, frequent URIs and some learning problems; NO corneal clouding

Question 8

Hurler

Answer 8

AR

• enzyme deficiency- alpha iduronidase +Treatment*
• *Similar to Hunter (can occur in girls); Coarse facies, HSM, major skeletal problems, corneal clouding**

developmental delay, gargoyleism, airway obstruction, corneal clouding, HSM

Question 9

McArdie

Answer 9

AR
enzyme deficiency-Glycogen phosphorylase

Muscle cramping after exercise; myogolbuinuria (coffee colored urine after exercise)

Muscle weakness and cramping, normal liver enzymes, normal cognition, chronic condition, myoglobinuria (coffee-colored urine after exercise) more of a glycogen storage disease

Question 10

1) A 25 year old woman with a history of hepatosplenomegaly with eventual splenectomy, bone and joint pain, and a liver biopsy that showed wrinkled
-looking cells (‘or foamy macrophages’) with accumulations of glucosylceramides. The
most likely
diagnosis is:

A) Fabry disease B) Farber disease C) Gaucher disease D) Krabbe disease E) Niemann-Pick disease

Answer 10

Gaucher

Question 11

2) Mucopolysaccharidoses are inherited storage diseases caused by:
A) an increased rate of synthesis of proteoglycans
B) the synthesis of polysaccharides with an altered structure
C) defects in the degradation of proteoglycans
D) the synthesis of abnormally small amounts of protein cores
E) an insufficient amount of proteolytic enzymes

Answer 11

C) defects in the degradation of proteoglycans

Question 12

3) A 13 month old child who died
at home had been suffering from cardiomegaly and progressive muscle weakness for the past five
months. Prior to death his electrocardiogram showed
rapid conduction time and wide amplitude QRS complex. A skeletal muscle biopsy showed elevated glycogen. Of the following, the most likely diagnosis is:
A)Fabry Disease
B)Hurler disease
C)Pompe disease
D)Tay-Sachs disease
E)Von Gierke’s disease

Answer 12

C)Pompe disease

Question 13

4)A 13 month old child who died at home had been suffering from cardiomegaly and progressive muscle weakness for the past five months. Prior to death his electrocardiogram showed rapid conduction time and wide amplitude QRS complex. A skeletal muscle
biopsy showed elevated glycogen. Which of the following enzymes is most likely to be deficient:
A) Alpha - galactosidase
B) Alpha-glucosidase
C) Alpha-iduronidase
D) Glucocerebrosidase
E) Sphingomyelinase

Answer 13

B) Alpha-glucosidase

Question 14

5)  A 3-year-old girl is seen in clinic for frequent otitis media infections, and a history of developmental delay.  On exam, she has severe growth retardation, corneal opacities, hepatosplenomegaly, and coarse facial features. Which of the following diseases is the patient likely affected with?
A)Hurler
B)Hunter disease
C)Pompe disease
D)Tay Sachs disease 
E)Von Gierke’s disease

Answer 14

A)Hurler

Question 15

6) A 47-year-old man is seen in clinic for a 5-year history of
a hearing defect, moderate intellectual disability, and valvular heart disease. The eye examination reveals a clear cornea. The defective enzyme is found to be iduronate sulphate sulfatase. The most likely diagnosis is:
A)Hurler
B)Hunter disease
C)Pompe disease
D)Sandhoff disease
E)Tay-Sachs disease

Answer 15

B)Hunter disease

Question 16

7) A 7-month old male infant is brought to medical attention because of progressive loss of motor and developmental skills and the recent onset of seizures. On examination you note poor visual tracking, mild muscle hypertonicity, an increased startle reflex. Ophthalmologic examination shows bilateral cherry red
-spots. The most likely diagnosis is:
A)Fabry disease
B)Hunter disease
C)Pompe disease
D)NiemannPick disease
E)Tay Sachs disease

Answer 16

E)Tay Sachs disease

Question 17

8)  A 7 month old female infant is brought to medical attention because of progressive loss of motor and developmental skills and the recent onset of seizures.  On examination you note poor visual tracking, mild muscle hypertonicity, an increased startle reflex.  
Ophthalmologic examination shows bilateral cherry red
-spots.  The most likely diagnosis is:
A) Alpha galactosidase
B) Alpha glucosidase 
C) Beta hexosaminidase A
D) Glucocerebrosidase
E) Sphingomyelinase

Answer 17

C) Beta hexosaminidase A

Question 18

9) A 25 year - old woman presents to clinic complaining of muscle weakness and pain. She tells you that she has noted progressive decline of exercise capacity for the past six years. She continues to try and exercise and reports that she has great difficulty at the beginning of her aerobics class, but if she rests for 10-20 minutes she
often gets a ‘second wind’ and can then rejoin her class. She competed in a 5K run last year and had significant myalgias after the race as well as particularly dark urine for two days after the race. An important complication of this disorder is:
A) Adrenal failure
B) Heart failure
C) Hepatic failure
D) Pancreatic failure
E) Renal Failure

Answer 18

E) Renal Failure

Question 19

10) A 18 year old man complains of a multi year history of recurrent painful episodes involving his palms and the soles of his feet. He also has a history of irritable bowel
syndrome and has been hospitalized twice for heat
- intolerance this past summer. His past medical
history is remarkable for two clavicular fractures, myopia, and one hospitalization for pneumonia. Which of the following tests is most likely to reveal his diagnosis:
A)24 hour urine collection and urinary creatinine
measurement
B) Alpha - galactosidase activity in leukocytes
C) Bone survey X rays
D) Echocardiogram
E) Serum ionized ca

Answer 19

B