Unit 7 - Introduction to Medical Genetics Flashcards

1
Q

inherited VS acquired disease

A

inherited gene complement - mutations may be transmitted from one or both parents (constitutional genome)
-present since birth

acquired gene complement - subset of cells in an individual that arose by clonal propagation from a single mutation in one cell
-arises later in life

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2
Q

what is a syndrome?

A

set of characteristics which occur together and are assumed to have a common basis

  • not all characters occur in all affected individual
  • range of variability within a population
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3
Q

what is biochemical genetics?

A

subspecialty of genetics that deals with diagnosis, treatment, and research of inborn errors of metabolism

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4
Q

what are inborn errors of metabolism?

A

genetically determined biochemical disorder where a specific enzyme defect produces a metabolic block

  • accumulation of substrate
  • deficiency of products
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5
Q

alcaptonuria

A

accumulation of homogentisic acid due to defect in homogentisic acid oxidase in blood damages cartilage, heart, and kidney

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6
Q

what causes albinism?

A

defect in tyrosine oxidase prevents pigment formation

-can be complete (no pigment in any organ/tissue, plus red eyes) or partial (some organs or tissue have pigment)

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7
Q

what are 3 types of hyperphenylalaninemias?

A

phenylketonuria
variant PKU
defects in BH4

related to function of phe hydroxylase

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8
Q

when does PKU occur?

A

AR mutation of phe hydroxylase (PAH) prevents phe –> tyr, causing phe accumulation

  • small fraction of phe is converted to phenylpyruvic acid to be detected in urine
  • must be treated early and in pregnancy by diet modification
  • -even if fetus is non-PKU, mother’s exccess PKU can cross placenta and damage fetus
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9
Q

what is non-PKU hyperphenylalaninemia?

A

10x increase in phe levels (decrease in phe hydroxylase, but still functional)

  • less damaging, may be benign
  • may not require special diet
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10
Q

variant PKU

A

between full PKU and non-PKU hyperphenylalaninemia

-requires diet, but not as restrictive as PKU patients

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11
Q

defect in BH4 metabolism

A

1-3% of hyperphenylalaninemia patients

  • non-mutant phe hydroxylase gene, but mutant DHPR gene (qBH4 –> BH4)
  • patients don’t completely respond to PKU diet and develop neurological defects
  • thus, supplement with oral BH4 for PAH problem, and L-dopa or OH-trp for sopamine/NE/E and serotonin pathways, respectively
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12
Q

lysosomal storage diseases

A

recessive due to mutation of lysosomal hydrolytic enzyme that leads to failure of degradation and accumulation of macromolecules in lysosomes

  • over 50 known deficiencies, and clinically heterogeneous
  • common presentation is progressive degeneration as organelles become larger, so affected organs/tissues increase in mass
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13
Q

how does GM2 gangliosidoses come about?

A

lysosomal storage disease; 3 genes make 3 PRO that function together
-alpha, beta subunits (come together to form dimer) and activator protein)

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14
Q

Tay Sachs disease?

A

AR, onset of 3-6 mo, and death in 2-4 years

  • deficiency of hexosaminidase A, unable to degrade GM2 ganglioside
  • no known treatment, so GM2 builds up in lysosomes and die between 2-4 years
  • have cherry red spot in retina of eye
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15
Q

mucopolysaccharidoses symptoms and cause

A

group of heterogenous disorders

  • absence of specific enzyme involves in degradation of glycosaminoglycans
  • accumulation of macromolecules in lysosomes
  • most are AR, but Hunter syndrome is XLR
  • permanent, progressive damage
  • short stature, delay, skeletal abnormalities, joint stiffness, thickened skin, heart/liver/spleen damage
  • some diseases are more severe than others, are progressive, and worsen over time
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16
Q

treatment for mucopolysaccharidoses

A
  • bone marrow transplantation
  • enzyme replacement therapy
  • gene therapy
17
Q

osteogenesis imperfecta symptoms and cause

A

due to mutations in type I collagen with either reduced collagen production or defective collagen

  • 4 major classes that range from mild to lethal, all AD
  • -I - mildest; reduced collagen production (collagen made in half the normal quantity, causing brittle bones)
  • -II - perinatal lethal
  • -III - between II and IV
  • -IV - mild to moderate bone deformity and fracturing
  • major character is brittle bones and skeletal deformities
18
Q

Ehler-Danlos syndrome

A

error in post-translational modification of collagen (primarily COL5A or COL3A genes) with multiple subtypes (AD, AR, and XLR)
-have fragile skin, joint hypermobility, and skin hyperextensibility

19
Q

Marfan syndrome symptoms and causes

A

connective tissue disorder of fibrillin gene

  • primary targets are skeleton, heart, lungs, and eyes
  • tall and thin, with very long fingers, joint laxity, and scoliosis
  • lung problems cause pneumothorax
  • dislocation of lens or myopia are common findings
  • cataracts, glaucoma, and retinal detachment are additional problems
  • heart issues include mitral valve prolapse, dilatation, and dissection of aorta (common death cause is rupture of thin aorta)
20
Q

Marfan syndrome treatment

A

no known cure, but effective management

  • know limits, limit stress
  • surgical repair of aorta is possible
  • orthopedic braces and devices help skeletal issues, and there are well-established management programs for eye problems