Genetics Test 2

  1. Abnormality of structure, function or metabolism
    birth defect
  2. Inborn Erros of Metabolism
    • ~1 in 500 newborns (not rare)
    • Many present at neonatal interval
    • Signs and symptoms are nonspecific
  3. Normal parents, one affected offsprin, typcially one affected generation. (Parental recurrence risk is 1 in 4 in each subsequent pregnancy)
    Autosomal Recessive
  4. Consanguinity and incest issues found in what type of inheritance?
  5. Affected males in multiple generations are maternally related by unaffected carrier females.
    X-linked inheritance patterns
  6. Recurrence risk for X-linked inheritance.
  7. Half the sons of a carrier mother will be affected and half of her daughters are carriers.

    Lyonization issues
    X-linked inheritance pattern
  8. Proband-based testing:  Diagnostic, confirmatory test... it has
    High specificity
  9. Population screening:  Complex health initiatives, newborn has
    High sensitivity
  10. Ecogenetic Concerns: 
    Includes locus and allelic heterogeneity.  Genotype classification is needed.
    Genetic Heterogeneity
  11. Ecogenetic Concerns:  Metabolic tolerance will change with physiologic maturation and the catabolic stress of fasting.
    Clinical heterogeneity
  12. Goal in multidisciplinary management issues:
    • Ecogenetic control
    • Overall goal: support the family
  13. Urine Odor:
    Musty or mousy
  14. Urine Odor:
    Maple Syrup
    Maple Syrup Urine Disease
  15. Urine Odor: 
    Sweaty feet
    • Isovaleric acidemia
    • Glutaric Aciduria II
  16. Urine Odor:
    Rotting fish
  17. Urine Odor:
    Tomcat urine
  18. Urine Odor:
    Rancid or "fishy"
  19. Urine Odor:
    Methionine malabsorption
  20. PKU is negative for low glucose, metabolic acidosis, ketosis, and elevated ammonia
  21. Elevated galactose, galactose-1 phosphate and galactitol.
    Urine reducing substances (galactose).
    GALT Deficiency
  22. Name 2 things found in GALT deficiency.
    • Hemolytic anemia
    • Unconjugated hyperbilirubinemia
    • Hepatomegaly (liver failure)
    • Cataracts
    • Cerebral edema
  23. Which disease has static encephalopathy (not reversed by galactose restriction)
    GALT Deficiency
  24. What is the rate of female infertility in hypergonadotropic hypogonadism (GALT Deficiency)?
    • >75% female infertility
    • Elevated LH and FSH
  25. In Galactosemia managment you use formulas derived from
    soybeans (or hydrolysates)
  26. What things can give you false-negative test for GALT.
    • Blood transfusion
    • Before they start breast-feeding
  27. What can give you false-positive test rate for GALT Deficiency?
    Improper processing of newborn screening cards and mailing them during hot, humid summer months.
  28. What 3 things do the MS Newborn Screen identigy?
    GALT, GALE,  GALK deficiency
  29. GALK
    Galactokinase Deficiency
  30. UDP Galactose-4-epimerase deficiency
  31. Galactose-1-phosphate uridyltransferase deficiency
    Classic galactosemia
  32. Two different recessive alleles that work at the same gene.
    Compound heterozygote
  33. Blood Levels of Phenylalanine
    Atypical PKU:
    • >2
    • 10-15
    • 2-10
  34. Phenylalanine Neurotoxicity:  Acute or Chronic?
    Irreversible CNS damage in infancy and childhood
    Acute phenylalanine neurotoxicity
  35. Phenylalanine Neurotoxicity:  Acute or Chronic?
    Functional impairment and progressive neuropsychiatric abnormalities later in life.
    Chronic Phenylalanine Neurotoxicity
  36. Incidence of Tetrahydrobiopterin deficiency is about __% that of hyperphenylalaninemia due to ____ mutations.
    1%, PAH
  37. Major symptom of PKU
    Profound mental retardation (IQ <35) in about 50%
  38. Phenylketonuria: Folling's Ferric Chloride "Diaper" Test for?
    Urinary Phenylpyruvate
  39. Inhibition of bacterial growth by B-2-thienylalanine is overcome by phenylalanine that diffuses out of the blood spot.
    Guthrie Screening Test (PKU)
  40. Confirmation of PKU Diagnostic Testing in Newborns shows _____ levels of plasma phenylalanine and _____ levels of tyrosine.
    Increase phenylalanine, normal tyrosine
  41. Phenylalanine is an ______
    essential amino acid
  42. Restriction of dietary phenylalanine is recommended for all infants with plasma levels greater than?
    6 mg/dL
  43. How many people with PKU have not been identified?
  44. BMI=
    (Weight in Kg)(Stature in meters)2
  45. Children with optimally managed PKU appear normal but may have significant problems.
  46. Phenylketonuria therapy:  Tetrahydrobiopteran (BH4) cofactor therapy
  47. Pregnancy in a woman with hyperphenylalaninemia is a high-risk event.  The highest fetal risk is in women with intrapartum plasma phenylalanin levels greater than
    18 mg/dL
  48. Poor maternal compliance in PKU leads to children with
  49. Clinical features include:
    Eye:  Ectopia, lentis, myopia
    Skeleton:  Osteoporosis, biconcave vertebrae
    CNS: Mental retardation
  50. What is a critical factor in the health of individuals with IEM?
    Protein catabolism
  51. MCADD (Medium Chain Acyl CoA Dehydrogenase Deficiency)
    • AR
    • Sudden onset, very rapid progression
  52. 1st event:  ALTE, SIDS
  53. Hypoketotic hypoglycemia (Low-moderate urinary ketones, Hypoglycemia)
    Hypoketotic Hypoglycemia
  54. How do you manage MCADD?
    • Avoid prolonged fasting (including Night feedings)
    • IV glucose and early hospitalization are necesary if there is emesis or if adequate oral intake to maintain normal glucose levels are needed.
  55. Rate of MCAD Deficieny in US.
    Carrier Frequency?
    • 1/16,000
    • Carrier Frequency = 1/60
  56. Propionic or Methylmalonic Acidemia normal metabolism is dependent on ?
    Biotin & B12
Card Set
Genetics Test 2
Bayesian, Mitochondrial, etc.