Genetics 5 Flashcards
Chromosome 9. Gene FXN. GAA repeat
Friedich ataxia
Nervous tissue destruction in spinal cord. Low levels of frataxin protein in mitochondria . Gene? Chromosome?
Chromosome 9
Gene FXN
Repeat GAA
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.
Chromosome 9
Gene FXN
GAA
Friedreichs ataxia
Diminished sense of vibration and lropioception. Absent DTRs. (Arreflexia)
Distal weakness. Nystagmus.
Child of 7 years old.
Friedreich ataxia
Gene FXN
GAA
Chrom 9
Most common cause of death in mutation of FXN,chrom 9, GAA repeat
Fridreich ataxia
FXN gene
Chromosome 9
Repeat GAA
MCCof death: hypertrophic cardiomyopathy seen in 50% of patients.
Cardiac defects in mutation of FXN gene, chr 9 repeat GAA
Hypertrophic cardiomyopathy, murmurs and conduction problems
Endocrine problemas seen in gene FXN mutation, chro 9, repeat GAA,
Friedeicj ataxia
Diabetes mellitus
Patient of 15 years old. Kyphoscoliosis, Les cabusm hannertoes, nystagmus, hypertrophic cardiomyopathy sx.
Frideichs ataxia
Gene FXN
Chr 9
Repeat GAA
FANCA, FANCC, FANCG, inhibit gene repair
Fanconi anemia
Fanconi anemia associated with increased risk of ——- (leukemia)
AML
Short stature, dermatological issues, risk of AML, decreased rbcells, decreased WBcells, decreased platelets (bone marrow failure).
Brushing, Petechial, superficial bleeding
Man in his 40s
Fanconi anemia
Fanconi anemia. Genes mutated.
Majority of cases, three genes: FANCA
FANCC, FANCG
Minimum of 15 genes, though 3 involved in majority of cases, cause this disease.
Fanconi anemia
Gene FANCA
FANCC
FANCG
Benign spilling of galactose into urine
Galactouria
Galactosuria deficiency?
Enzyme galactokinase, GALK1 gene
Chromosome 17
Galactosuria, gene?
Chromosomes?
Gene GALK1
Chromosome 17
Worrisome complication in GALK1 deficiency.
Cataracts.
Galactouria
Gene GALK1
Chromosome 17
Cataracts in galactouria caused by accumulation of ——- in the lens of the patient during first weeks or months of life
Galactitol
——- is the enzyme that turns galactose into galactitol and also turns glucose into sorbitol
Aldole reductase
How to treat Galactouria?
Eliminate lactose and galactose from diet.
Remove cataracts.
Deficiency of galactose 1 phosphate uridiltransferase (UDP)
Causes galactosemia
Accumulation of gallatose 1 P causes
Galactosemia
Newborn with feeding problems, failure to
Thrive, liver damage/failure, bleeding, infections,
Deficiency in galactose 1 P UDP
Galactosemia
Without treatment galactosemia can lead to
Hyperamonemia,
sepsis - leading to shock and death, developmental delays - psychological and motor.
Management of galactosemia
Restrict or eliminate galactose from diet because thes elatients have not the enzyme galactose 1 P URidultransferase UDP
Most common lysosomal storage disease, dysfunctional metabolism of sphingolipids.
Defective GBA gene
Gaucher disease
Deficiency of ——— enzyme, characterizes Gaucher’s disease. Gene?
Gluco cerebro sidase enzyme
Gene GBA
Accumulation of beta- glucocerebrosidase within cells of liver, brain, bone marrow, kidney spleen and lungs.
Macrophages look like tissue drooled paper in the cell.
Gaucherie disease
Gene GBA
Accumulation of Beta gluco cerebro sidase
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
Gaucher’s disease types 1,2 and 3.
What types of Gaucher’s disease could be managed by replacement of the deficient enzyme ———?
Types 1 and 3.
Give enzyme beta gluco cerebrosidese
(Expensive, however)
GLB1 gene mutation. Two types Gm1 and Gm2 deficiency?
Beta galactosidase
Neurodegeneration, seizures, H/S Magaly, coarsening of facial features, skeletal abnormalities, lipid storage disease seen in early infants, severe form of GLB1 gene mutation
GM1 gangliosidosis caused by def in enzyme beta galatosidase
Gene GLB1
Late infantile form of this lipid storage deficiency presents in 1-3 years old withataxia, seizure, dementia, speech difficulties
GM1 gangliosidosis, gene GLB1, lipid storage disorder
Tay Sachs
GM2 gangliosidosis, askenazi jews, lipids accumulate in nervous system,
GM2 gangliosidosis
Cherry red macula,
Blindness, psychomotor retardation, death before 2 years of age
Tay Sachs
Deficiency in beta hexosaminidase A
Gm 2 gangliosidosis, Tay sachs disease
Deficiency?
Beta hexosaminidase A
Affects absorption of non polar Aa, most importantly Trptophan
Mutation?chromosome?
Chromosome 5
Gene SLC 6A19
What aa does tryptophan make?
Niacin
Serotonin
Melatonin
Are made by it.
Why is niacin important? What does it make?
Important because it makes NAD+
If deficiency in niacin occurs then —-,—-,—- and —- Occur.
De,entra, dermatitis, diarrhea d if not treated then possibly death.
MEchanism for harnup disease. Chromosome?
Chromosome 5
Gene SLC 6A19
MOO: impedes transport of neutral aa in intestines and kidneys.
Sx of FTT, pellagra, photosensitivity, nystagmus, ataxias- intermittent, increased neutral aa in urine
Hartnup disease
Chro 5
Gene SLC 6A19
These recommendations manage what?
High protein in diet, avoiding sunlight and drugs that may cause hyper sensitivity
Harnups disease management
Defect in the IDUA gene, chromosome 4
Hurlers syndrome
Inheritance of Hurler syndrome?
Autosomal recessive
In hurlers Syndrome there is deficiency of what enzyme? Accumulation of what?
Alpha L Iduronidase
Se acumulan Heparan sulfate
Dermatan sulfate
Child. Deaf, blind, coarse features
Hurler Syndrome
Autosomal recessive
Chromosome 4
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.
Hurlers Syndrome
Management for hurlers Syndrome
Replace enzyme
Hemochromatosis gene? Chro?
Gene HFE, chr 6
Abnormally high absorption of iron in GI,gene? Chro?
Gene HFE
Chr 6
Hemochromatosis
Where is the most important site for HFE expression?
Basolateral surface of small intestine
Hemochromatosis
Hemochromatosis associated with two things
Liver cirrhosis
Hepatocellular carcinoma
In mutations of HFE gene, chr 6, the iron accumulates in
Heart, pancreas (bronze diabetes or sickly gray skin), liver (cirrhosis, hepatocellukar carcinoma) and testicles
Mutation in GALC, chrom 14
Krabbes disease
In mutations of GALC , chro 14, there is deficiency of enzyme
Galacto- cerebro sidase causing degeneration of Myelin sheath in the CNS
Deficiency of galacto cerebro sidase causing myelin degeneration in CNS
Krabbes disease,chrom 14, gene GALC
Irritability, Fever, feeding difficulty, vomiting, seizures, mental motor regression, spasticity, deafness, optic nerve atrophy, muscle weakness, problem in GALC
Krabbes disease, degenerates myelin,
Chro 14
Gene GALC
deficiency of galacto cerebrosidase
Management of a deficiency on galacto cerebrosidase
Bone marrow transplant
Chr, 14
Gene GALC
Primary cikiary dyskinesia, Dunedin arm defect, sperm can’t move, cilia can’t move, situs inversus
Kartagener syndrome
Why are people with kartageners syndrome prone to mucocikiary infections?
No cilia action movement. So no cleaning of pathogens.
Situs inversus with dextrocardia would look show up like what
Right axis deviation
Disruption of formation of integrins, which are needed for migration of leukocytes from vascular space to tissues,
Leukocyte adhesion def
In leukocyte adhesion def there is a genetic absence of which integrins?
CD18
Late separation of umbilical cord. Poor wound healing. Recurring skin infections. Gingival inflammation.
Leukocyte adhesion deficiency
This enzyme if required for breakdown of leucine, valine, isoleucine
Branched-chain alpha keto acid dehydrogenase complex
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?
Metacheomatic leukodystrophy
In metachromatic leukodystrophy. Enzyme def?
Aryl sulfatase A, buildup of sulfatides in tissue and destruction of myelin in both CNS and PNS.
Multiple sclerosis sx in children. Dx?
Metachromatic leukodystrophy
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.
Metachromatic leukodystrophy
Inheritance of metachromatic leukodystrophy
Autosoma recessive
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,
Metachromatic leukodystrophy
Def in aryl sulfatase A enzyme
Inheritance of sickle cell disease?
Autosomal recessive
Hemolysis, vaso occlusive sx, infections. Mc in African Americans
Sickle cell disease
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.
Sickle cell disease
Encapsulated organisms (name 6)
Strep pneumonia, pseudomonas aeruginosa, salmonella, meningitidis , hemophilous influenza , cryptococcus neoformans
Person cannot make dopamine, epinephrine or norepinephrine. Why?
Def in phenylalanine hydroxylase
PKU
Light skin, blonde eyes, blue eyes, musty odor, hypopigmentation, intellectual deficiencies,
PKU
Def in phenylalanine hydroxylase
In PKY the body cannot convert ——- into ——-
Phenylalanine into tyrosine, this cannot make dopamine, NE y epi. Or melanin.
What causes the musty odor in PKY?
Accumulation of
- Phenylacetate
- phenylpyruvate
- Phenethylamine
Inheritance of Wilson’s disease
Autosomal recessive
Inheritance of PKU?
Autosomal recessive
Inheritance of metachromatic leukodystrophy
Autosomal recessive
Toxic accumulation of copper in eyes, liver, brain. And kidney. Mutation? Chrom?
Wilson’s disease
Chro 13
Gene ATP 7B
Young patient (kid or teenager) with Parkinsonism (cogwheel rigidity bradykynesia, ataxia, dystonia)
Wilson’s disease
Chr 13
Gene ATP 7B
Teenager with parksinonism, hepatimegaly, and arthritis
Wilson’s disease
Chro 13
Gene ATP 7B
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.
ATP 7B protein
Ceruloplasmin
What things are Dx for Wilson’s disease?
- Káiser fleischer rings - pathognomonic, seen with a lamp
- Neuropsychiatric sx like Parkinsonism
- High serum copper
- Urinary copper with no hepatitis
- low ceruloplasmin
What is the cause of Kaiser fleischer rings?
Accumulation of copper in the descements layer
Management of Wilson’s?
Chelator Penicillamine
Diet low in copper
Copper tends to accumulate, when in the brain, in the
Basal ganglia, generating psychosis and Parkinson’s
