FA Lysosomal and Glycogen Storage Diseases

Question 1

What is the inheritance of Glucose-6-phosphatase deficiency

Answer 1

Auto Recessive

Question 2

What is the likely diagnosis for an 6m old with fasting hypoglycemia, enlarged abdomen, seizures, and increased serum triglycerides?

Answer 2

Von Gierke Disease: Glucose-6-phosphatase def. The enlarged abdomen is from hepatomegaly.

Question 3

What would serum levels of glucose, lactate, triglycerides, and uric acid be in a patient with Von Gierke Disease? Enzyme def?

Answer 3

Glucose-6-phosphatase. Fasting hypoglycemia, increased lactate, TGs, and uric acid.

Question 4

Management for Glucose-6-phosphatase deficiency

Answer 4

Frequent oral glucose/cornstarch. Avoid Fructose/Galactose.

Question 5

What is the inheritance of Lysosomal alpha-1,4-glucosidase deficiency? Other names for this enzyme?

Answer 5

Auto Recessive. Other names for alpha glucosidase are acid maltase and Acid alpha-glucosidase

Question 6

What are symptoms of Glucose-6-phosphatase deficiency?

Answer 6

Fasting hypoglycemia, hepatomegaly, seizures, increased serum triglycerides, lactate, and uric acid.

Question 7

What is likely diagnosis for an infant presents with enlarged cardiac silhouette, lethargy, floppy limbs, and poor feeding.

Answer 7

Pompe Disease. Acid alpha-glucosidase Deficiency.

Question 8

What are classic symptoms of Pompe Disease? Enzyme deficiency?

Answer 8

Cardiomegaly, Hypertrophic cardiomyopathy (Pompe trashes the Pump), exercise intolerance (in older kids), hypotonia in infants (floppy baby), lethary. Presents similar to other glycogen storage disorders but cardiac signs help with ddx.

Question 9

What are classic biopsy findings of muscle from a kid with pompe disease? What is the deficient enzyme in pompe?

Answer 9

Lysosomal alpha-1,4-glucosidase. Enlarged lysosomes with glycogen build up, appears as clear inclusions filling myocytes.

Question 10

What enzyme deficiency is associated with Cori Disease? What disease is Cori a milder form of? Inheritance pattern?

Answer 10

Debranching enzyme deficiency, also called alpha-1,6,-glucosidase. Auto Recessive. Milder form of Von Gierke Disease (Glucose-6-phosphatase deficiency)

Question 11

Is gluconeogenesis intact in Cori Disease? What are levels of lactate?

Answer 11

Yes, normal levels of lactate. Lactate levels increased in Von Gierke Disease.

Question 12

Most likely lysosomal/glycogen storage disease diagnosis for an 11 y/o female with muscle pain, coffee colored urine, and arrhythmia after playing a soccer game.

Answer 12

McArdle Disease: Skeletal muscle glycogen phosphorylase deficiency (myophosphorylase)

Question 13

Inheritance pattern for McArdle Disease? Deficient enzyme?

Answer 13

Auto recessive. Skeletal muscle glycogen phosphorylase.

Question 14

What are typical blood glucose levels of a patient with McArdle Disease?

Answer 14

Usually normal

Question 15

Are there any options to manage McArdle Disease?

Answer 15

B6=Pyridoxime

Question 16

What do all Glycogen storage diseases have in common?

Answer 16

Accumulation of Glycogen within cells

Question 17

Fabry disease is due to a deficiency of??? Inheritance pattern?

Answer 17

X Recessive. alpha-galactosidase A

Question 18

Most likely enzyme deficiency in a young male with acroparethesias and angiokeratomas?

Answer 18

alpha-galactosidase A; Fabry’s Disease. X-linked.

Question 19

What is the most concerning consequence of fabry’s disease?

Answer 19

TIA/Stroke due to cardiac hypertrophy secondary to untreated renal damage. Life Expectancy is 40 in males.

Question 20

A decifiency in alpha-galactosidase A will result in the accumulation of what?

Answer 20

Ceramide trihexoside

Question 21

What is the most common lysosomal storage disease?

Answer 21

Gaucher Disease

Question 22

A cherry red spot on the macula makes you think of what two diseases?

Answer 22

Tay-Sachs and Niemann-Pick

Question 23

What is the most likely disease in an adult with hepatosplenomegaly, anemia, and thrombocytopenia. Enzyme Deficient?

Answer 23

Gaucher Disease. Glucocerebrosidase (Beta-glucosidase). Auto recessive.

Question 24

What lysosomal storage diseases are inherited in a autosomal recessive manner?

Answer 24

Gaucher, Niemann-Pick, Tay-Sachs, Krabbe, Metachromatic Leukodystrophy, and Hunter Syndrome.

Question 25

Accumulation of what is seen in this cell?

Answer 25

Glucocerebroside d/t lack of Beta-glucosidase (Glucocerebrosidase). Gaucehr cells are "lipid laiden macrophages resembling "crumpled tissue paper""

Question 26

what are the signs of Gaucher disase? Deficient enzyme?

Answer 26

Glucocerebrosidase: Hepatosplenomegaly, pancytopenia, osteoporosis, aseptic necrosis of bone, Gaucher cells on histology.

Question 27

Most likely diagnosis in a 6m old with progressive loss of motor skills, a large abdomen, and a red spot on the macula? Enzyme Deficiency?

Answer 27

Sphingomyelinase; Niemann-Pick Disease. Life expectancy is 3 years. Large abdomen is likely due to hepatosplenomegaly. KEY=HSM, Tay-Sachs have similar presentation but w/o the HSM.

Question 28

Looking at this liver sample from a 5m old kid. What are you thinking (besides, "I hate histology and it all looks pink and purpkle)

Answer 28

These are foamy macrophages. "Foam macrophages" is FA's buzz word for Niemann-Pick disease. these cells also look like the lipid-laiden macrophages in liver from a patient with Gaucher.

Question 29

What is the inheritance of a diase that results in the accumulation of Sphingomyelin? Deficient enzyme?

Answer 29

Auto. Recessive. Sphingomyelinase is deficienct in Niemann-Pick disease.

Question 30

Most likely enzyme deficiency in an infant who is not latching well to the breast and has progressive loss of motor coordination, a red spot on the macula, and normal abdominal exam.

Answer 30

Hexosaminidase A deficient; Tay-Sachs. Key=No HSM vs. HSM seen in Niemann-Pick.

Question 31

First aid thinks it is important to mention that what disease is seen in Ashkenazi Jewish, Pennsylvania Dutch, and Louisiana Cajuns. Bonus: Which group makes the best food?

Answer 31

Tay-Sachs has greater incidence in these groups. And of course, Axhkenazi's with their pasta and cereal (Kasha Varnishkes)

Question 32

Light microscopy and EM have the corresponding findings from an infant with progressive neurodegereration. What disease are these findings associated with? What is accumulating in the cells?

Answer 32

Light microscopy shows neurons with large lipid vacuoles while the EM shows "onion skinning" lysosomes. Findings are consistent with the accumulation of GM2 Ganglioside d/t deficient Hexosaminidase (Tay-Sachs)

Question 33

What is the disease and inheritance pattern associated with a patient who is described to have developmental delays, peripheral neuropathy and optic atrophy?

Answer 33

Auto recessive. Krabbe disease, a deficiency in Galactocerebrosidase.

Question 34

Globoid cells should cue you in on what enzyme deficiency? What is the associated accumulated substrate?

Answer 34

Galactocerebrosidase; Krabbe disease. Galactocerebroside/psychosine.

Question 35

You see a kid with ataxia, dementia, and metachromic granules on histology what enzyme is likely dificient in this patient?

Answer 35

Arylsulfatase A; Metachromatic leukodystrophy. Neuro deficiets are due to central and peripheral demyelination.

Question 36

Arylsulfatase deficiency will lead to the accumulation of...? Inheritance pattern of this disease?

Answer 36

Cerebroside Sulfate. Auto recessive.

Question 37

The accumulation of mucopolysaccharidoses is possible in what USMLE important diseases?

Answer 37

Hurler and Hunter Syndromes

Question 38

You see a coarse-appearing child, who is short, has a hoarse voice, frequent URIs and some learning problems. What is the most likely diagnosis? What enzyme is deficient?

Answer 38

Hurler Syndrome. Alpha-L-iduronidase. Hurler Syn is characterized by devo delay, gargoylism, airway obstruction, corneal clouding, and hepatosplenomegaly. KEY: Presents just like Hunter but Hunter DOES NOT HAVE CORNEAL CLOUDING

Question 39

Your attending tells you that your patient may have Hurler or Hunter Syndrome. What question could you ask to help decide? What are the inheritance patterns?

Answer 39

Hunter=no corneal clouding, Hurler=Corneal Clouding. Hunter=auto recessive, Hurler=X-linked recessive.

Question 40

What are the accumulated substrates for Hunter and Hurler?

Answer 40

Both accumulate Heparan sulfate/Dermatan Sulfate.

Question 41

Deficient enzyme in Hunter syndrome?

Answer 41

Iduronate sulfatase

Question 42

what skin lesions can be seen in both hurler and hunter?

Answer 42

pearly, papular lesions