Diseases Flashcards
1
Q
- autosomal recessive disorder
- mutation in both alleles of PAH gene on chromosome 12 leading to deficiency in phenylalanine hydroxylase (PAH)
- Symptoms: mental retardation, organ damage, unusual posture, microcephaly, seizures, hyperactivity, musky diaper smell
- Milder form: hyperphenylalanemia
- Can also be caused by mutation in genes involved in production or recycling of tetrahydrobiopterin (BH4)
- Accumulation of phenylalanine (normal is
A
Phenylketonuria (PKU)
2
Q
- converts phenylalanine to tyrosine by hydroxylating the phenolic ring
- deficiency causes accumulation of phenylalanine leading to PKU
A
Phenylalanine Hydroxylase (PAH)
3
Q
- a cofactor of PAH
A
Tetrahydrobiopterin (BH4)
4
Q
- autosomal recessive
- Caused by frameshift mutation of TATC insertion in exon 11 of HEXA gene on chromosome 15 leading to deficient Hexosaminidase A enzyme
- accumulation of GM2 ganglioside in the brain
- Common in Ashkenazi Jews
- Symptoms: progressive neurological deterioration until death at 2-4 yrs if affected as infant, cherry-red spot in retina,
- In later onset: vision and intelligence remains normal, spinocerebellar degeneration (lower motor neuron dysfunction and ataxia), psychosis
A
Tay-Sachs Disease
5
Q
- cleaves the terminal N-acetyl-B-galactosamine residue from the ganglioside
- composed of alpha subunit (HEXA) and beta subunit (HEXB)
- requires an activator protein
A
Hexosaminidase A
6
Q
- autosomal recessive
- mannose-6-phosphate defect
- defect in Golgi-specific N-acetylglucosamine-1-phosphotransferase by mutation in GNPTAB on chromosome 12q23.2 which leads to a defect in protein trafficking
- abnormal lysosomes (inclusion bodies)
- Symptoms: unusual facial features, skeletal changes, severe growth retardation, mental retardation, increased acid hydrolases levels in body fluids
A
I-Cell Disease
7
Q
- autosomal recessive
- deficiency in cystathionine B-synthase, methionine synthase, Vit B6 deficiency, Folate, or B12
- Symptoms: dislocation of the lens, mental retardation, osteoporosis, long bones, thromboembolism of the veins and arteries
A
Homocystinuria
8
Q
- autosomal recessive
- associated with chronic obstructive lung disease (emphysema) and liver cirrhosis
- inherited conformational disease - changes the shape or size of a protein
- mutation in Z allele (Glu342Lys) leading to formation of long bead-like necklaces of mutant a1AT polymers
- Symptoms: SOB, cough or wheeze, rhonchi, can develop emphysema, cirrhosis
A
a1-Antitrypsin Deficiency
9
Q
- a serine protease inhibitor (serpin)
- binds to and inhibits activity of elastase
- methionine 358 oxidized by cigarette smoke and inflammatory cells reducing affinity for elastase
A
a1-Antitrypsin
10
Q
- autosomal dominant
- caused by mutation in gene encoding for porphobilinogen (PBG) deaminase (PBGD) on chromosome 11
- occurs in response to events that decrease concentration of heme in liver cell [barbiturates, drugs, steroid hormones, surgery]
- Symptoms: GI and neuropathic episodes, abdominal pain, vomiting, confusion, emotional, hallucinations, psychosis
A
Acute Intermittent Porphyria
11
Q
- autosomal dominant
- elevated plasma cholesterol carried by LDL
- mutation in LDL receptor (chr 19), ApoB-100 (chr 2), PCSK9 protease (chr 1), or ARH adaptor protein (chr1)
- symptoms: premature heart disease, xanthomas, arcus corneae
A
Familial Hypercholesterolemia
12
Q
- autosomal recessive
- Caucasian children (1/2000; 1/25 carriers)
- Mutation of CFTR gene at deltaF508, C to T, Phe to Ile
- Chromosome 7q31
- Symptoms: recurrent lung infections, positive salt sweat test, large greasy stools light in color with foul odor, congenital bilateral absence of the vas deferens, infertile
- Diagnostic feature: increased concentrations of sweat Na+Cl-
A
Cystic Fibrosis
13
Q
- X-linked
- age of onset about 3-5 years
- progressive muscle weakness, awkward gait, pseudohypertrophy of calves, Gower maneuver, lordosis, death by 18 due to cardiorespiratory failure
- elevated serum level of creatine kinase (CK)
- absence of dystrophin
- most often a frameshift mutation deletion of the dystrophin gene (60%)
- considered a “genetic lethal” condition
A
Duchenne Muscular Dystrophy
14
Q
- X-linked
- age of onset about 11 years
- progressive muscle weakness, awkward gait, pseudohypertrophy of calves, but ambulant into adult life, decreased life span
- truncated dystrophin
- inframe deletion mutation of dystrophin gene (60%)
A
Becker Muscular Dystrophy
15
Q
- joint hypermobility, cutaneous fragility, cigarette paper skin, hyperextensibility
- genetic defect in collagen structure, synthesis, secretion, or degradation
A
Ehlers-Danlos Syndromes (EDS)
16
Q
- mutations in loci containing COL5A1 or COL5A2 genes encoding the alpha-chains of Type V collagen
- autosomal dominant
- skin and joint hypermobility, atrophic scars, easy bruising
A
Classical EDS (Type I and II)
17
Q
- Autosomal Dominant
- joint hypermobility, pain, dislocations
A
EDS Type III
18
Q
- decreased amount of Type III collagen (reticulin)
- mutation in COL3A1
- Thin skin, arterial or uterine rupture, bruising, small joint hyperextensibility
- autosomal dominant
A
EDS Type IV
19
Q
- autosomal recessive
- deficiency in lysyl hydroxylase
- hypotonia, joint laxity, congenital scoliosis, ocular fragility
A
EDS Type VI
20
Q
- severe skin fragility, cutis laxa, bruising
- procollagen N-peptidase
A
EDS Type VIIc
21
Q
- autosomal dominant
- severe joint hypermobility, mild skin changes, scoliosis, bruising
- defect in COL1A1, COL1A2
A
EDS Type VIIa,b
22
Q
- autosomal recessive
- extreme sensitivity to UV radiation and multiple skin cancers
- marked freckling of face, xerosis, poikiloderma, corneal opacification
- result from lack of nucleotide-excision repair
A
Xeroderma Pigmentosa
23
Q
- drug that inhibits the calcium pump in the rough ER
- used to prevent calcium-dependent chaperone that traps mutant CFTR protein and impairs its binding in ER for degradation
A
Curcumin
24
Q
drug that allows the ribosome to bypass a premature stop codon at relatively low frequency and enables increased expression of full length protein
A
Gentamycin
25
Q
- autosomal dominant
- mutation in gene for APC, tumor suppressor gene on chromosome 5q21-q22
- thousands of polyps on the colon which have potential to form a malignant tumor
A
Familial Adenomatous Polyposis (FAP)
26
Q
- protein misfolding of Amyloid Precursor Protein (APP) creating neurotoxic peptide (AB-42)
- B-amyloid neuritic plaques
- neurofibrillary tangles
- abnormal cleavage of amyloid precursor protein by alpha, beta, gamma secretases
- Tau protein normally organizes microtubules but abnormal post-translation hyperphosphorylation causes tangles
- Mutation in PSEN1&2 (cofactor of gamma secretase)
- e4 of APOE mutation also causes build of up APOE plaques
- progressive deterioration of memory and higher cognitive functions, agitation, social withdrawal, hallucinations, seizures, rigidity, mutism, eventually bed ridden and will die from malnutrition, infection or heart disease
A
Alzheimer’s Disease
27
Q
- mitochondrial disorder
- mutation in tRNA for Lysine
- A->G transition @8344
- myopathy, sensineural deafness, dementia, epilepsy, ataxia
- dx made from: myoclonus, generalized epilepsy, ataxia, ragged red fibers
- Structurally and biochemically abnormal mitochondria appear red in muscle tissue
A
MERFF (myoclonic epilepsy with ragged red fibers)
28
Q
- mitochondrial disorder
- point mutation in tRNA for leucine, translation of codons for leucine
- A->G transition @3242
- affects many of the body’s systems (brain, nervous system, muscles)
- muscle weakness, vomiting, seizures, diabetes, vision loss, dementia, deafness, lactic acidosis, stroke like episodes at age 40
A
MELAS (Mitochondrial Encephalopathy, Lactic Acidosis and Stroke)
29
Q
- mutation of Abelson (ABL) proto-oncogene by translocation 9 (ABEL) and 22 (BCR)
- symptoms: enlarged spleen, joint/hip pain, low-grade fever, anemia, thrombocytopenis
A
CML (chronic myologenous leukemia)
30
Q
drug that that prevents fusion protein BCR-ABL from binding ATP so it can’t phosphorylate it’s substrates that are involved in enhanced growth of leukemia cells
A
Gleevec (imantinib)
31
Q
- autosomal dominant
- results from mutations in genes coding for proteins involved in mismatch repair
- most common mutations are in MLH1 and MSH2 genes for MutL and MutS
- Microsatellite instability
A
HNPCC
32
Q
- caused by mutation in tumor suppressor gene
- Rb1 gene, Rb protein - chrom 13
- early symptom is white reflex in cornea of eye while shining a light
A
Retinoblastoma
33
Q
- Symptoms include mental retardation and macroorchidism and deep plantar creases
- X-linked dominant
- Caused by abnormal CGG repeat >200 leading to hyper-methylation of 5’ UT and decreased FMR1 expression
- gain of function
A
Fragile X Syndrome
34
Q
- B cell tumor of the jaw
- translocation between chromosomes 8 and 14
- c-myc proto-oncogene on 8q24 translocated distal to the immunoglobin heavy chain(IGH) locus at 14q32
- IGH enhancer upregulates c-myc and converts it to oncogene
- common in children in equatorial Africa
- other possible translocations: IGL 22 lambda, 2 kappa
A
Burkitt Lymphoma
35
Q
- use to treat sickle cell
- cytosine analog incorporated into gamma globin gene promoter
- causes hypomethylation of HbF, increasing adult HbF
A
Decitabine
36
Q
- autosomal recessive
- deficient in ADA
- leads to accumulation of deoxyadenosine
- T and B cell lymphotoxicity leads to SCID
A
Adenosine Deaminase Deficiency
37
Q
What does PAH do?
A
- converts phenylalanine to tyrosine by hydroxylating the phenolic ring
38
Q
Individuals with PKU are often what?
A
compound heterozygoes
39
Q
- autosomal recessive
- a-L-iduronidase deficiency (chromosome 4)
- corneal clouding, coarse facies, skeletal abnormalities, hepatosplenomegaly, hearing loss, progressive and profound mental retardation, linear growth ceases, death by cardiorespiratory failure
A
Hurler Syndrome
40
Q
What are the 6 types of defects that can cause homocystinuria?
A
- classic homocystinuria due to defective cystathionine synthase
- methylene-h4-folate reductase defects (impairs methionine synthase)
- defects in the intracellular metabolism of cobalmins which affect methionine synthase
- direct affect on methyl-b12 formation
- cobalmin intestinal absorption
- abnormalities in the major extracellular transport protein, transcobalamin II
41
Q
How are all defects in cobalamin metabolism inherited?
A
autosomal recessively
42
Q
anemia that results from inhibition of DNA synthesis in red blood cell production
- due to a deficiency of vitamin B12 and/or folic acid
- characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow
A
Megaloblastic anemia
