Autosomal Recessive Disorders

Question 0

What is the autosomal recessive disorder where a point mutation of HBB gene on c11 producing HbS, glutamic acid changed to valine at position 6 in beta-hemoglobin chain?

Answer 0

Sickle Cell

Question 1

What are characteristics of autosomal recessive disorders?

Answer 1

• usually skips a generation common with consanguinity/inbreeding (consanguinity seen more commonly in rare diseases)
• complete penetrance
• males and females equally affected
• 25% AA (affected), 50% Aa (unaffected carrier), 25% aa (unaffected)
• 25% chance each child born after one affected child produced will be clinically affected, 50% chance each child will be carrier
• 100% chance of transmitting the gene to each child for an affected individual
• heterozygotes have 50% of normal function usually

Question 2

What autosomal recessive disorder has the recurrence risk of 1/625 for African American 1/160,000 for Caucasians?

Answer 2

Sickle Cell

Question 3

What autosomal recessive disorder has the following phenotype:
- variation in clinical manifestations: often severe lifelong hemolytic anemia. Failure to thrive, hemosiderosis, gallstones, splenomegaly in children, fibrotic spleen in adults, vascular problems, dactylitis/infections, resistance to malaria, severe pain in the limbs, back, chest and abdomen. Three main pathological findings: chronic hemolysis, microvascular occlusion so nitric oxide down and adhesion markers up, tissue damage, vascular structure leads to tissue infarction?

Answer 3

Sickle Cell

Question 4

What autosomal recessive disorder is diagnosed by screen for HbS with meta bisulfide. Gold standard test is hemoglobin electrophoresis to identify HbS. DNA analysis can be done in prenatal testing.

Answer 4

Sickle Cell

Question 5

In what autosomal recessive disorder to RBC’s sickle with hypoxia or low pH. Heterozygotes are asymptomatic unless oxygen levels are very low and are resistant to malaria. Sickle cells return to their normal shape due to an influx of calcium, decrease of potassium and oxygen or an increase in membrane damage. ~50% of patients survive beyond 5th decade

Answer 5

Sickle Cell

Question 6

What autosomal recessive disorder has a CFTR gene deletion at 7q31 delta-F508 most common?

Answer 6

Cystic Fibrosis

Question 7

What autosomal recessive disorder has a recurrence risk of 1/2500 in Caucasians,1/15,000 African Americans, 1/31,000 Asians

Answer 7

Cystic Fibrosis

Question 8

What autosomal recessive disorder has the following phenotype:
Neonatal - meconium ileus, abdominal or scrotal calcifications
Infant - persistent filtrates on chest radiographs, failure to thrive, chronic diarrhea, staph aureus pneumonia
Childhood - chronic pansinusitis or nasal polyposis, rectal prolapse, inussusception, idiopathic recurrent or chronic pancreatitis
Adult- allergic brochopulmanary aspergillosis, chronic pansinusitis or nasal polyposis, brochiectasis, pancreatitis, delayed puberty, azoospermia due to absence of vas deferens

Answer 8

Cystic Fibrosis

Question 9

What autosomal recessive disorder can be diagnosed with a sweat chloride test?

Answer 9

Cystic Fibrosis

Question 10

What autosomal recessive disorder is fully penetrant, chloride transport channels are non-functional b/c of protein formation error, heterozygotes (carriers) have protection against diarrheal diseases such as cholera and typhoid

Answer 10

Cystic Fibrosis

Question 11

What are examples of autosomal recessive disorders?

Answer 11

Sickle Cell

Cystic Fibrosis