Genetics 5

Question 1

Chromosome 9. Gene FXN. GAA repeat

Answer 1

Friedich ataxia

Question 2

Nervous tissue destruction in spinal cord. Low levels of frataxin protein in mitochondria . Gene? Chromosome?

Answer 2

Chromosome 9
Gene FXN
Repeat GAA

Question 3

Most commonly see. In children between 5 and 15 years old. Progressive ataxia of 4 limbs. Nystagmus. Dysmetria. Dysarthria (impaired speech production). Dx? Gene? Chromosome.

Answer 3

Chromosome 9
Gene FXN
GAA
Friedreichs ataxia

Question 4

Diminished sense of vibration and lropioception. Absent DTRs. (Arreflexia)
Distal weakness. Nystagmus.
Child of 7 years old.

Answer 4

Friedreich ataxia
Gene FXN
GAA
Chrom 9

Question 5

Most common cause of death in mutation of FXN,chrom 9, GAA repeat

Answer 5

Fridreich ataxia
FXN gene
Chromosome 9
Repeat GAA

MCCof death: hypertrophic cardiomyopathy seen in 50% of patients.

Question 6

Cardiac defects in mutation of FXN gene, chr 9 repeat GAA

Answer 6

Hypertrophic cardiomyopathy, murmurs and conduction problems

Question 7

Endocrine problemas seen in gene FXN mutation, chro 9, repeat GAA,

Answer 7

Friedeicj ataxia

Diabetes mellitus

Question 8

Patient of 15 years old. Kyphoscoliosis, Les cabusm hannertoes, nystagmus, hypertrophic cardiomyopathy sx.

Answer 8

Frideichs ataxia
Gene FXN
Chr 9
Repeat GAA

Question 9

FANCA, FANCC, FANCG, inhibit gene repair

Answer 9

Fanconi anemia

Question 10

Fanconi anemia associated with increased risk of ——- (leukemia)

Answer 10

AML

Question 11

Short stature, dermatological issues, risk of AML, decreased rbcells, decreased WBcells, decreased platelets (bone marrow failure).
Brushing, Petechial, superficial bleeding
Man in his 40s

Answer 11

Fanconi anemia

Question 12

Fanconi anemia. Genes mutated.

Answer 12

Majority of cases, three genes: FANCA

FANCC, FANCG

Question 13

Minimum of 15 genes, though 3 involved in majority of cases, cause this disease.

Answer 13

Fanconi anemia
Gene FANCA
FANCC
FANCG

Question 14

Benign spilling of galactose into urine

Answer 14

Galactouria

Question 15

Galactosuria deficiency?

Answer 15

Enzyme galactokinase, GALK1 gene

Chromosome 17

Question 16

Galactosuria, gene?

Chromosomes?

Answer 16

Gene GALK1

Chromosome 17

Question 17

Worrisome complication in GALK1 deficiency.

Answer 17

Cataracts.
Galactouria
Gene GALK1
Chromosome 17

Question 18

Cataracts in galactouria caused by accumulation of ——- in the lens of the patient during first weeks or months of life

Answer 18

Galactitol

Question 19

——- is the enzyme that turns galactose into galactitol and also turns glucose into sorbitol

Answer 19

Aldole reductase

Question 20

How to treat Galactouria?

Answer 20

Eliminate lactose and galactose from diet.

Remove cataracts.

Question 21

Deficiency of galactose 1 phosphate uridiltransferase (UDP)

Answer 21

Causes galactosemia

Question 22

Accumulation of gallatose 1 P causes

Answer 22

Galactosemia

Question 23

Newborn with feeding problems, failure to

Thrive, liver damage/failure, bleeding, infections,

Answer 23

Deficiency in galactose 1 P UDP

Galactosemia

Question 24

Without treatment galactosemia can lead to

Answer 24

Hyperamonemia,

sepsis - leading to shock and death, developmental delays - psychological and motor.

Question 25

Management of galactosemia

Answer 25

Restrict or eliminate galactose from diet because thes elatients have not the enzyme galactose 1 P URidultransferase UDP

Question 26

Most common lysosomal storage disease, dysfunctional metabolism of sphingolipids. Defective GBA gene

Answer 26

Gaucher disease

Question 27

Deficiency of ——— enzyme, characterizes Gaucher’s disease. Gene?

Answer 27

Gluco cerebro sidase enzyme Gene GBA Accumulation of beta- glucocerebrosidase within cells of liver, brain, bone marrow, kidney spleen and lungs.

Question 28

Macrophages look like tissue drooled paper in the cell.

Answer 28

Gaucherie disease Gene GBA Accumulation of Beta gluco cerebro sidase

Question 29

Type 1 in ashkenazi Jews, non neuropathic, hepatosplenomegaly. Type 2 is fatal. Presents within 6 months of age. h/S Magaly, neuro findings, extensive brain damage, seizures, poor sucklingand swallowing reflexes, death within first few years of life Type 3 is chronic neuropathic form From childhood to adulthood, Slowly progressinG neuro sx Live into teens or adulthood

Answer 29

Gaucher’s disease types 1,2 and 3.

Question 30

What types of Gaucher’s disease could be managed by replacement of the deficient enzyme ———?

Answer 30

Types 1 and 3. Give enzyme beta gluco cerebrosidese (Expensive, however)

Question 31

GLB1 gene mutation. Two types Gm1 and Gm2 deficiency?

Answer 31

Beta galactosidase

Question 32

Neurodegeneration, seizures, H/S Magaly, coarsening of facial features, skeletal abnormalities, lipid storage disease seen in early infants, severe form of GLB1 gene mutation

Answer 32

GM1 gangliosidosis caused by def in enzyme beta galatosidase | Gene GLB1

Question 33

Late infantile form of this lipid storage deficiency presents in 1-3 years old withataxia, seizure, dementia, speech difficulties

Answer 33

GM1 gangliosidosis, gene GLB1, lipid storage disorder

Question 34

Tay Sachs

Answer 34

GM2 gangliosidosis, askenazi jews, lipids accumulate in nervous system,

Question 35

GM2 gangliosidosis Cherry red macula, Blindness, psychomotor retardation, death before 2 years of age

Answer 35

Tay Sachs | Deficiency in beta hexosaminidase A

Question 36

Gm 2 gangliosidosis, Tay sachs disease | Deficiency?

Answer 36

Beta hexosaminidase A

Question 37

Affects absorption of non polar Aa, most importantly Trptophan Mutation?chromosome?

Answer 37

Chromosome 5 | Gene SLC 6A19

Question 38

What aa does tryptophan make?

Answer 38

Niacin Serotonin Melatonin Are made by it.

Question 39

Why is niacin important? What does it make?

Answer 39

Important because it makes NAD+

Question 40

If deficiency in niacin occurs then —-,—-,—- and —- Occur.

Answer 40

De,entra, dermatitis, diarrhea d if not treated then possibly death.

Question 41

MEchanism for harnup disease. Chromosome?

Answer 41

Chromosome 5 Gene SLC 6A19 MOO: impedes transport of neutral aa in intestines and kidneys.

Question 42

Sx of FTT, pellagra, photosensitivity, nystagmus, ataxias- intermittent, increased neutral aa in urine

Answer 42

Hartnup disease Chro 5 Gene SLC 6A19

Question 43

These recommendations manage what? | High protein in diet, avoiding sunlight and drugs that may cause hyper sensitivity

Answer 43

Harnups disease management

Question 44

Defect in the IDUA gene, chromosome 4

Answer 44

Hurlers syndrome

Question 45

Inheritance of Hurler syndrome?

Answer 45

Autosomal recessive

Question 46

In hurlers Syndrome there is deficiency of what enzyme? Accumulation of what?

Answer 46

Alpha L Iduronidase Se acumulan Heparan sulfate Dermatan sulfate

Question 47

Child. Deaf, blind, coarse features

Answer 47

Hurler Syndrome Autosomal recessive Chromosome 4

Question 48

Umbilical or inguinal hernia seen at birth Hepatosplenomegaly, macrocephaly, hydrocephalus, gargoilysm , visual deterioration, clouding of cornea, hearing loss, progressive mental retardation, death by first decade of life.

Answer 48

Hurlers Syndrome

Question 49

Management for hurlers Syndrome

Answer 49

Replace enzyme

Question 50

Hemochromatosis gene? Chro?

Answer 50

Gene HFE, chr 6

Question 51

Abnormally high absorption of iron in GI,gene? Chro?

Answer 51

Gene HFE Chr 6 Hemochromatosis

Question 52

Where is the most important site for HFE expression?

Answer 52

Basolateral surface of small intestine | Hemochromatosis

Question 53

Hemochromatosis associated with two things

Answer 53

Liver cirrhosis | Hepatocellular carcinoma

Question 54

In mutations of HFE gene, chr 6, the iron accumulates in

Answer 54

Heart, pancreas (bronze diabetes or sickly gray skin), liver (cirrhosis, hepatocellukar carcinoma) and testicles

Question 55

Mutation in GALC, chrom 14

Answer 55

Krabbes disease

Question 56

In mutations of GALC , chro 14, there is deficiency of enzyme

Answer 56

Galacto- cerebro sidase causing degeneration of Myelin sheath in the CNS

Question 57

Deficiency of galacto cerebro sidase causing myelin degeneration in CNS

Answer 57

Krabbes disease,chrom 14, gene GALC

Question 58

Irritability, Fever, feeding difficulty, vomiting, seizures, mental motor regression, spasticity, deafness, optic nerve atrophy, muscle weakness, problem in GALC

Answer 58

Krabbes disease, degenerates myelin, Chro 14 Gene GALC deficiency of galacto cerebrosidase

Question 59

Management of a deficiency on galacto cerebrosidase

Answer 59

Bone marrow transplant Chr, 14 Gene GALC

Question 60

Primary cikiary dyskinesia, Dunedin arm defect, sperm can’t move, cilia can’t move, situs inversus

Answer 60

Kartagener syndrome

Question 61

Why are people with kartageners syndrome prone to mucocikiary infections?

Answer 61

No cilia action movement. So no cleaning of pathogens.

Question 62

Situs inversus with dextrocardia would look show up like what

Answer 62

Right axis deviation

Question 63

Disruption of formation of integrins, which are needed for migration of leukocytes from vascular space to tissues,

Answer 63

Leukocyte adhesion def

Question 64

In leukocyte adhesion def there is a genetic absence of which integrins?

Answer 64

CD18

Question 65

Late separation of umbilical cord. Poor wound healing. Recurring skin infections. Gingival inflammation.

Answer 65

Leukocyte adhesion deficiency

Question 66

This enzyme if required for breakdown of leucine, valine, isoleucine

Answer 66

Branched-chain alpha keto acid dehydrogenase complex

Question 67

Lysosomal storage disease. Myelin is destroyed in CNS and PNS. In late infantile form: developmental delays, difficulty walking around 2nd year of life, muscle rigidity, wasting and paralysis of swallowing muscles, loss of vision porgressive, dementia and possibly coma. Dx?

Answer 67

Metacheomatic leukodystrophy

Question 68

In metachromatic leukodystrophy. Enzyme def?

Answer 68

Aryl sulfatase A, buildup of sulfatides in tissue and destruction of myelin in both CNS and PNS.

Question 69

Multiple sclerosis sx in children. Dx?

Answer 69

Metachromatic leukodystrophy

Question 70

This lysosomal storage disease strikes between 3-10 years old. Poor school performance, progressive sx of mental deterioration, dementia plus sx of late infantile form develop. Def in Aryl sulfatase A enzyme.

Answer 70

Metachromatic leukodystrophy

Question 71

Inheritance of metachromatic leukodystrophy

Answer 71

Autosoma recessive

Question 72

Whcih lysosomal storage dosease should be included in a differential that includes schizophrenia, drugs and wilson’s Disease Presenting in a 16 year old with psychiatric disturbances that progress to dementia?developes slowly over the course of a decade or more. Considered a terminal illness. No cure,

Answer 72

Metachromatic leukodystrophy | Def in aryl sulfatase A enzyme

Question 73

Inheritance of sickle cell disease?

Answer 73

Autosomal recessive

Question 74

Hemolysis, vaso occlusive sx, infections. Mc in African Americans

Answer 74

Sickle cell disease

Question 75

African American man with increase in indirect bilirubin concentration and increased levels of lactate DH, dactylitis with swelling, warmth and pain of hands and foot, sausage digits, erythematous inflamed digits, predisposed to infections with encapsulated organisms.

Answer 75

Sickle cell disease

Question 76

Encapsulated organisms (name 6)

Answer 76

``` Strep pneumonia, pseudomonas aeruginosa, salmonella, meningitidis , hemophilous influenza , cryptococcus neoformans ```

Question 77

Person cannot make dopamine, epinephrine or norepinephrine. Why?

Answer 77

Def in phenylalanine hydroxylase | PKU

Question 78

Light skin, blonde eyes, blue eyes, musty odor, hypopigmentation, intellectual deficiencies,

Answer 78

PKU | Def in phenylalanine hydroxylase

Question 79

In PKY the body cannot convert ——- into ——-

Answer 79

Phenylalanine into tyrosine, this cannot make dopamine, NE y epi. Or melanin.

Question 80

What causes the musty odor in PKY?

Answer 80

Accumulation of 1. Phenylacetate 2. phenylpyruvate 3. Phenethylamine

Question 81

Inheritance of Wilson’s disease

Answer 81

Autosomal recessive

Question 82

Inheritance of PKU?

Answer 82

Autosomal recessive

Question 83

Inheritance of metachromatic leukodystrophy

Answer 83

Autosomal recessive

Question 84

Toxic accumulation of copper in eyes, liver, brain. And kidney. Mutation? Chrom?

Answer 84

Wilson’s disease Chro 13 Gene ATP 7B

Question 85

Young patient (kid or teenager) with Parkinsonism (cogwheel rigidity bradykynesia, ataxia, dystonia)

Answer 85

Wilson’s disease Chr 13 Gene ATP 7B

Question 86

Teenager with parksinonism, hepatimegaly, and arthritis

Answer 86

Wilson’s disease Chro 13 Gene ATP 7B

Question 87

In Wilson’s disease, there is a problem wit( protein ——- such that copper in the liver isn’t incorporated to ——. Thus, it accumulates in the liver, leading to oxidative damage.

Answer 87

ATP 7B protein | Ceruloplasmin

Question 88

What things are Dx for Wilson’s disease?

Answer 88

1. Káiser fleischer rings - pathognomonic, seen with a lamp 2. Neuropsychiatric sx like Parkinsonism 3. High serum copper 4. Urinary copper with no hepatitis 5. low ceruloplasmin

Question 89

What is the cause of Kaiser fleischer rings?

Answer 89

Accumulation of copper in the descements layer

Question 90

Management of Wilson’s?

Answer 90

Chelator Penicillamine | Diet low in copper

Question 91

Copper tends to accumulate, when in the brain, in the

Answer 91

Basal ganglia, generating psychosis and Parkinson’s