NBME - 6/12 - Disorders of AA and Nucleotide Metabolism

Question 1

What is PKU? What chromosome mutation is involved with it?

Answer 1

Phenylketonuria is an AR disorder involving severe decrease in phenylalanine hydroxylase, leading to a buildup of phenylalanine.

The gene is located on Chromosome 12

Question 2

PKU progression in children clinically

Answer 2

These kids are hyperactive, have purposeless movements, rhythmic rocking and athetosis.

We smell a musty odor secondary to phenylacetic acid, and these guys can develop seizures

Question 3

Infants of mothers who have too much Phenylalanine during pregnancy

Answer 3

They are mentally retarded and may have microcephaly and/or congenital heart defects

Question 4

How does PKU present initially?

Answer 4

Normal infant at first, but mental retardation begins with an estimated loss of 50 IQ points in the first 12 months. If left untreated, it increases in severity.

Other early symptoms include vomiting, which can be misdiagnosed as pyloric stenosis

Question 5

What is tyrosinemia?

Answer 5

This is an error of metabolism due to lack of fumarylacetoacetate hydrolase (FAH).

This is the most frequent autosomal recessive enzyme issue.

The body cannot break down tyrosine, leading to liver and kidney issues as well as mental retardation

Question 6

Tyrosinemia in infants

Answer 6

Begins as failure to thrive and hepatomegaly, progressing to liver and kidney dysfunction

Question 7

What liver manifestations of Tyrosinemia do we see?

Answer 7

Causes cirrhosis, conjugated hyperbilirubin, increased AFP, coagulation abnormalities and decreased blood sugar.

This leads to jaundice, ascites, hemorrhage, and puts you at an increased risk for hepatocellular carcinoma (50% of the these children by age 2)

Question 8

Kidney manifestations of Tyrosinemia

Answer 8

Fanconi Syndrome - Renal Tubular Acidosis, hypophosphatemia, aminoaciduria

Question 9

Besides the liver and kidney, Tyrosinemia can creep up in other locations. What are they?

Answer 9

• Cardio
• Neuro
• Derm

Question 10

How do we treat tyrosinemia?

Answer 10

First line therapy is just a low protein diet, but eventually, transplant of the liver is needed.

Question 11

What is A1AT deficiency?

Answer 11

Autosomal recessive disorder marked by abnormally low or no serum A1AT in the blood. It is the most common cause of liver disease in kids and emphysema in adults.

Question 12

What does A1AT normally do?

Answer 12

This is a protease inhibitor made by the liver that inhibits neutrophil elastase released by WBCs

Question 13

A1AT deficiency presents how?

Answer 13

Leads to fatigue and SOB due to the lung damage, as well as jaundice that can lead to hepatitis and cirrhosis if it affects the liver.

Question 14

How does A1AT damage the liver?

Answer 14

In response to tissue injury or inflammation, A1AT in this disease still responds, it just can’t get out of the ER, polymerizing with it. Accumulation damages the hepatocytes.

Question 15

How can we see A1AT deficiency in the lab?

Answer 15

Immunostaining and EM for the neonatal and light microscopy after 3 months

Question 16

What is albinism?

Answer 16

Congenital disorder characterized by complete or partial absence of pigment secondary to absence or defect in tyrosinase, a copper enzyme involved with melanin production from Tyrosine.

It affects about 1:16,000 in U.S.

Question 17

Hallmark of albinism besides the skin

Answer 17

Eye changes. All of them can be seen (Nystagmus, strabismus, astigmatism, photophobia, foveal hypoplasia, optic nerve hypoplasia, abnormal decussation of optic nerves at the optic chiasm, ambylopia, really anything you can think of)

Question 18

What causes Gaucher Disease?

Answer 18

This is an autosomal recessive disorder caused by deficiency of glucocerebrosidase, the lysosomal enzyme that degrades sphingolipids with terminal residues in a B linkage

Question 19

Who gets Gaucher Disease and what chromosome do we associate with it?

Answer 19

Ashkenazi Jews

Chromosome 1 (1q21-q31)

Question 20

Discuss the three types of Gaucher Disease

Answer 20

1 - Young adults, mild to severe effects with no CNS involvement and some glucocerebrosidase activity

2 - Infants. Die in infancy and it affects the CNS. Very little glucocerebrosidase activity

3. Children and young adults - Late onset CNS that becomes very severe with little glucocerebrosidase activity.

Question 21

Clinical presentation of Gaucher disease

Answer 21

Splenomegaly is usually the first sign. Storage of glucocerebroside in the spleen and bone marrow leads to Anemia, Leukopenia, and Thrombocytopenia

Question 22

Most common way to diagnose Gaucher

Answer 22

Bone marrow biopsy

Question 23

How do we treat Gaucher?

Answer 23

Enzyme replacement therapy with macrophage-targeted glucocerebrosidase

Question 24

Signs of Acute hepatitis in Wilsons (remember, that Copper one that gets in your eye)

Answer 24

Ballooning degeneration, acidophilic bodies, cholestasis, lots of lymphocytes

Late you will see your mallory bodies like with alcoholism

Question 25

In Cystic Fibrosis, the problem is with CFTR. What does this do?

Answer 25

It regulates transport of electrolytes across epithelial cell membranes

Question 26

Most common manifestations of CF:

Answer 26

Pulmonary

Recurrent Pneumonias, particularly involving Psuedomonas aeruginosa.

Question 27

“____ in a neonate is CF until proven otherwise”

Answer 27

Meconium Ileus

Question 28

How do we diagnose CF?

Answer 28

Abnormal sweat chloride plus characteristic clinical findings of GI or pulmonary disease

Persistently elevated
concentrations of electrolytes in
the sweat (e.g., sweat chloride >60 mmol per liter; normal usually

Question 29

Genetic testing for CFTR issues?

Answer 29

Failure to find two abnormal genes does not rule out CF