Autosomal Recessive Disorders

Question 1

Denoted:

Answer 1

aa = affected 
Aa = carrier
AA = normal

Question 2

Cystic Fibrosis

Answer 2

“CFTR, 7q”
1 in 25
Abnormal fluid and electrolyte
Pulmonary Disease (chronic lung infection)
Pancreatic Defect (preventing normal digestion)
*Defect in male genital tract (males infertile due to bilateral absence of vas deferens (CBAVD) = azoospermia)
Meconium ileus
Hepatobiliar system

Increased in sweat Cl- level –> salty baby syndrome

CFTR Cl- 5 domains: 2 membrane spanning, 2 nucleotide (ATP) binding domains (NBDs), and 1 regulatory (R-domain) with multiple phosphorylations

Deletion of Phenylalanine at 508th position in 1st NBD = most common defect

Question 3

Tay Sach’s Disease

Answer 3

Lysosomal storage, sphingolipidoses
1:3600 
Retinal red spot 
Deficiency: Hexosaminidase A on Chrm 15
Hex A usuall catalyzes the degradation of GM2

Question 4

Hereditary Hemochromatosis

Answer 4

HFE gene mutation, cysteine replaced by tyrosine, leading INCREASED iron absorption in intestines than normal

Hyperpigmentation, diabetes, cirrhosis, and cardiomyopathy, iron overload

Serum ferritin increased

Females either less affected or unaffected
Usually seen in males

Question 5

Sickle Cell Anemia

Answer 5

Mutation Beta chain coding for HbA in Chrm 11
Glutamate replaced by Valine at 6th position

Forms HbS

HOMOzygotes - have Sickle Cell anemia in (e.g. for novel property mutation)

HETEROzygotes - advantage in MALARIA RESISTANCE

Question 6

Xeroderma Pigmentosum

Answer 6

Mutation of XP genes
Causes defective proteins required for nucleotide excision repair of pyrmidine-pyrimidine (thymine-thymine) dimer

UV light sensitivity, skin cancer, neurological dysfunction

Question 7

Alpha-1 Antitrypsin Deficiency

Answer 7

Missense mutation
Glutamate replaced by Lysine (like HbC)

Z/Z homozygotes, who also develop liver cirrhosis

Alpha-AT: usually a powerful inhibitor for neutrophil elastase in lung, preventing breakdown of lung elastin to protect lungs

Sx: shortness of breath, wheezng, cough

Question 8

Galactosemia

Answer 8

GALT, accumulate Galact-1-PO4, cataracts

Question 8

Phenylketonuria

Answer 8

Phenylalanine hydroxylase (PAH) or Dihydropteridine/Dihydrobiopterin reductase: microencephaly, urine mousy odor, IQ < 50, hypopigmentation

Question 9

Hurler syndrome

Answer 9

alpha-L-Iduronidase, CORNEAL CLOUDING

Question 10

Gaucher’s

Answer 10

Cerebrosidase/Beta-glucosidase, crumpled tissue paper

Question 11

Friedrich’s Ataxia

Answer 11

FRDA Gene, 1st intron, GAA expansion, frataxin protein, mitochondrial Fe-binding protein

associated with spinocerebellar ataxia