FA2015 - Biochem Chapter Diseases

Question 1

Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase -> Prevents DNA synthesis and thusly -> Decreased lymphocyte count. (Major cause of AR SCID)

Answer 1

Adenosine deaminase deficiency

Question 2

Defective purine salvage pathway. X-linked Recessive. Leads to hyperuricemia, gout, aggression and self mutilation, retardation and dystonia.

Answer 2

Lesch-Nyhan Syndrome. Absent HGPRT gene.

Question 3

Failure of Golgi to phosphorylate mannose residues leading to decreased mannose-6-phosphate on glycoproteins. Results in proteins not being trafficked to lysosomes. Coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes.

Answer 3

I-cell Disease. Defect in N-acetylglucosaminyl-1-phosphotransferase.

Question 4

Immotile cilia due to dynein arm defect. Results in male infertility, dysfunctional fallopian tubes, possible bronchiectasis, recurrent sinusitis, and situs inversus.

Answer 4

Kartagener Syndrome (Primary Ciliary Dyskinesia)

Question 5

AD disease. Defective production of type I collagen. Multiple fractures with minimal trauma, blue sclerae, hearing loss, dental imperfections. May be confused with child abuse.

Answer 5

Osteogenesis Imperfecta

Question 6

Defect in type V or type III collagen. Type V leads to joint and skin hyperlaxity. Type III leads to vascular and organ rupture. May be associated with joint dislocations, berry and aortic aneurysms, and organ rupture.

Answer 6

Type V: Classical Type Ehlers-Danlos Syndrome

Type III: Vascular Type Ehlers-Danlos Syndrome

Question 7

X-Recessive Disease, impaired copper absorption and trasports. Results in brittle, “kinky” hair, growth retardation and hypotonia.

Answer 7

Menkes Disease

Question 8

Maternal Imprinting Disease. Results in Hyperphagia, obesity, retardation, hypogonadism, and hypotonia.

Answer 8

Prader-Willi Syndrome

Question 9

Paternal Imprinting Disease. Results in inappropriate laughter (“happy puppet”), seizures, ataxia, and severe intellectual disability.

Answer 9

Angelman Syndrome

Question 10

Myopathy, lactic acidosis, CNS disease. Muscle biopsy often shows “ragged red fibers.”

Answer 10

Mitochondrial myopathies

Question 11

AR Disease. Defect in ATP Gated Cl- Channel. Results in thick mucus secretions. Diagnosed by Cl- sweat test.

Answer 11

Cystic Fibrosis. Tx: N-acetylcysteine (cleaves disulfide bonds within mucus glycoproteins.

Question 12

X-linked Defect in methylation and expansion of the FMR1 Gene. Post-pubertal macroorchidism, long face with large jaw, large everted ears, autism, MVP.

Answer 12

Fragile X Syndrome (CGG Repeats)

Question 13

Name the Trinucleotide Repeat Expansion Diseases

Answer 13

Huntington’s Disease (CAG)n
Fragile X Syndrome (CGG)n
Friedreich’s Ataxia (GAA)n
Myotonic Dystrophy (CTG)n

Question 14

Intellectual disability, flat facies, prominent epicanthal folds, single palmar crease. Increased risk of Hirshprung’s, ASD, early-onset alzheimer’s, ALL, AML.

Answer 14

Trisomy 21 - Down’s Syndrome
Dx: Low - AFP, Estriol
High - Beta-HCG, inhibin-A

Question 15

Severe Intellectual Disability, rocker-bottom feet, micrognathia (small jaw), low-set ears, clenched hands and overlapping fingers, congenital heart diseases, death usually within 1 year of birth.

Answer 15

Trisomy 18 - Edward’s Syndrome

Dx: Low - AFP, Estriol, Beta-HCG, Inhibin-A

Question 16

Severe Intellectual Disability, rocker bottom feet, micropthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, cutis aplasia.

Answer 16

Trisomy 13 - Patau Syndrome
Dx: Low - Beta-HCG, PAPP-A
Increased Nuchal Translucency

Question 17

Micro deletion of short arm of chromosome 5. Presents with microcephaly, moderate to severe intellectual disability, high-pitched crying or mewing, epicanthal folds, cardiac VSDs

Answer 17

Cri-du-chat Syndrome

Question 18

Micro deletion of long arm chromosome 7 (deleted region of elastin gene). Elfin facies, intellectual disability, hypercalcemia, well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems.

Answer 18

Williams Syndrome

Question 19

Micro deletion at chromosome 22q11. Cleft palate, abnormal facies, thymic aplasia, cardiac deficiencies, hypocalcemia.

Answer 19

DiGeorge Syndrome - thymic, parathyroid, and cardiac defects.
Velocardiofacial Syndrome - palate, facial, and cardiac defects.