Metabolic Disease and Genetics Flashcards
(93 cards)
1
Q
Thymic, Parathyroid and Cardiac Defects
A
DiGeorge Syndrome
2
Q
- Cleft Palate
- Abnormal Facies
- Thymic Aplasia –> T cell deficiency
- Cardiac Defects
- Hypocalcemia d/t parathyriod aplasia
CATCH 22
A
Microdeletion at Chromosome 22q11
3
Q
2 yo is presented to ED because of fever and has high pitched crying. Upon physical examination the following are noted:
1. Microcephaly
2. Moderate intellectual disability (can be severe)
3. Epicanthal folds
4. Cardiac abnormalties (VSD)
What is the congenital dz associated with this patient?
A
Cri-du-chat Syndrome
Cry of the cat
4
Q
What chromosomes are assoc with Robertsonian translocation?
A
Chromosomes 13, 14, 15, 21 and 22
5
Q
What chromosome is associated with:
- von Hippel Lindau dz
- Renal Cell Carcinoma
A
Chromosome 3
6
Q
What dz is associated with chromosome 4?
A
- APKD (PKD2)
- Achondroplasia
- Huntington dz
7
Q
What chromosome is associated with:
- Cri-du-chat syndrome
- Familial adenomatous polyposis (FAP)
A
Chromosome 5
8
Q
What dz is associated with chromosome 6?
A
Hemochromatosis (HFE)
9
Q
What chromosome is associated with:
- Williams Syndrome
- Cystic Fibrosis
A
Chromosome 7
10
Q
What chromosome is associated with:
Friedreich ataxia
A
Chromosome 9
11
Q
What dz is associated with Chromosome 11?
A
- Wilms Tumor
- Beta globin gene defects
a. Sickle cell dz
b. MEN1
c. Beta thalassemia
12
Q
What chromosome is associated with:
- Patau syndrome
- Wilson dz
- Retinoblastoma (RB1)
- BRCA2
A
Chromosome 13
13
Q
What dz is associated with chromosome 15?
A
- Prader-willi syndrome
- Angelman syndrome
- Marfan syndrome
14
Q
What chromosome is associated with:
A
Chromosome 16
15
Q
What chromosome is associated with:
- APKD (PKD1)
- alpha globin gene defects
a. Alpha thalessemia
A
Chromosome 16
16
Q
What dz is associated with chromosome 17?
A
- Neurofibromatosis 1
- BRCA1
- p53
- Li-Fraumeni
17
Q
What chromosome is associated with:
Edwards syndrome
A
Chromosome 18
18
Q
What dz is associated with chromosome 21?
A
Down Syndrome
19
Q
What chromosome is associated with:
- Neurofibromatosis 2
- Di George syndrome (22q11)
A
Chromosome 22
20
Q
What are some x-linked chromosomal dz?
A
- Fragile X syndrome (X-LD
- X-linked agammaglobulinemia
- Klinefelter syndrome (XXY)
- Alport Syndrome (X-LD)
- Hypophasphatemic Rickets (X-LD)
21
Q
What is imprinting?
A
At a loci one allele of the gene is inactive (imprinted/inactivated by methylation) and the other active allele is mutated or deleted
22
Q
What are 2 examples of imprinting?
A
Angelman Syndrome
Prader-willi Syndrome
23
Q
Which foods should be avoided in a patient with phenylketonuria
A
Foods containing phenylalanine (artificial sweeteners)
24
Q
How are the genes affected in Angelman syndrome?
A
MATERNAL Gene is mutated/deleted
Paternal Gene is inactivated (silent)
PATERNAL IMPRINTING
25
What is the clinical presentation associated with Angelman syndrome?
1. Inappropriate laughter ("happy puppet")
2. Seizures
3. Ataxia
4. Severe Intellectual disability
26
What is the clinical presentation associated with Prader-willi syndrome?
1. Hyperphagia
2. Obesity
3. Intellectual Disability
4. Hypogonadism
5. Hypotonia
27
What us the mode of inheritance when both males and females are affected?
Autosomal Dominant
28
Autosomal Dominant inheritance affects what type of genes?
Structural genes
29
Autosomal recessive inheritance is often related to.....
Enzyme deficiency
30
What mode of inheritance often presents in childhood and has increased risk in consanguineous families?
Autosomal Recessive
31
What is a distinguishing factor associated with Autosomal Recessive mode of inheritance?
Often seen in only 1 generation
32
Which mode of inheritance has features that are more severe in males and the females must be homozygous to be affected?
X-linked Recessive
33
What is a distinguishing feature of X-linked Recessive mode of inheritance?
1. No male to male transmission
| 2. Skips generations
34
What are the features associated with X-linked Dominant mode of inheritance?
1. Transmitted through both parents
2. Fathers transmit to daughters only (ALL)
3. Fathers do not transmit to sons
4. Mother transmit to 50% of daughters and sons
35
What is Hypophosphatemic Rickets aka Vit D rickets?
inc Phosphate wasting at proximal tubule --> Rickets like presentation
36
In which mode of inheritance is genes transmitted only through the mother?
Mitochondrial inheritance
37
In phenylketonuria what enzyme is deficient
Phenylalanine hydroxylase
38
What is the distinguishing feature of mitochondrial inheritance?
1. Heteroplasmy
2. Does not skip a generation
3. Clinical presentation is often seen after puberty
39
What becomes essential in Phenylketonuria
Tyrosine
40
Treatment for phenylketonuria
1. Decrease phenylalanine and increase Tyrosine in diet
| 2. Tetrahydrobiopterin supplementation (BH4)
41
What enzyme is deficient is Pompe disease
Alpha 1,4 glycosidase
42
In Maple syrup disease which amino acids cant be broken down
Branched amino acids (Leucine, isoleucine and valine)
43
What is the enzyme deficient in Cori disease
Debranching enzyme (alpha 1,6-gluconidase)
44
BLUISH BLACK connective tissue, ear cartilage and sclerae and urine turns BLACK on prolonged exposure to air
Alkaptonuria
45
Pt with cystic fibrosis can also present with what other issue?
Contraction alkalosis and hypokalemia
46
1. Recurrent pulmonary infections
2. Chronic Bronchitis
3. Bronchiectiasis
4. Pancreatic insufficiency
5. Absence of vas deferens = infertility in men
6. Liver dz
7. Biliary Cirrhosis
8. Nasal Polyps
9. Clubbing of nails
Complications associated with Cystic Fibrosis
47
What is the cause of CYSTINURIA
Defect of renal PCT and intestinal amino acid transport
48
Cystinuria leads to the malabsorption fo which amino acid
Cystine, Ornithine, Lysine and Arginine (COLA)
49
Who are affected in Mitochondrial inheritance?
All offsprings of affected female
50
What is the distinguishing feature of mitochondrial inheritance?
Heteroplasmy
51
What is heteroplasmy?
Variable expression of a mitochondrially inherited gene within a population or family.
52
Excess cystine in urine leads to the precipitation of which type of stones
Hexagonal cystine stones
53
What is the treatment for cystinuria
1. Urinary alkalinization (eg. potassium citrate,
acetazolamide) ,
2. good hydration, and
3. chelating agents ( eg. penicillamine)
54
What are some effects of mitochondrial mode of inheritance?
Rare disorders that tend to present with myopathy, lactic acidosis, and CNS dz (neuropathies)
55
What is an example of a clinical presentation of a pt with mitochondrial mode of inheritance of a dz?
```
1. MELAS Syndrome
Mitochondrial
Encephalopathy
Lactic
Acidosis
Stroke like episodes
2. Red ragged fibers on muscle biopsy
```
56
What is the diagnostic test for cystinuria
Urinary cyanide-nitroprusside test
57
Severe fasting HYPOGLYCEMIA or severe HYPOGLYCEMIA during exercise, Increased GLYCOGEN in the liver, increased blood lactate, triglycerides increased uric cid (gout) and hepatomegaly
Von Gierke Disease
58
In Von Gierke disease which enzyme is deficient
Glucose-6-phosphatase
59
What is the treatment for Von Gierke Disease
Oral glucose/ cornstarch
Avoidance of fructose and galactose
(impaired gluconeogenesis and glycogenolysis)
60
Cardiomegaly, hypertrophic cardiomyopathy, hypotonia, exercise intolerance
Pompe disease
61
What enzyme is deficient is Pompe disease
Alpha 1,4 glucosidase
62
Severe fasting hypoglycemia, increased glycogen in liver, NORMAL LACTATE levels and accumulation of limit dextrin-like structures in cytosol
Cori disease (typeIII)
63
What is the enzyme deficient in Cori disease
Debranching enzyme (alpha 1,6-gluconidase)
64
What causes Cystic Fibrosis?
Defect in CFTR gene on Chromosome 7 --> deletion of Phe508
65
What is the function of the CFTR gene?
encodes ATP gated CL channel that secretes CL in lungs and GI tract and reabsorbs CL in sweat glands
66
What is the effect of defect in CFTR gene?
dec. CL and H2O secretion
inc. intracellular CL
inc. Na reabsorption
inc. H2O reabsorption ==> abnormally thick mucus in lungs and GI tract
67
Increased glycogen in muscle but muscle cannot break it down leading to painful MUSCLE CRAMPS, MYOGLOBINURIA (red urine) with strenuous exercise
McArdle Disease
68
Myoglobinuria (red urine) with strenuous exercise and arrhythmia from electrolyte abnormalities. Second wind phenomenon noted during exercise due to increase muscular blood flow
Excercise
69
Which enzyme is deficient in McArdle Disease
Myophosphorylase
| ( cannot break down glycogen----> glucose--1--phosphate
70
1. Recurrent pulmonary infections
2. Chronic Bronchitis
3. Bronchiectiasis
4. Pancreatic insufficiency
5. Absence of vas deferens = infertility in men
Complications associated with Cystic Fibrosis
71
What is the tx for CF?
1. Chest physiotherapy
2. Albuterol
3. Hypertonis saline to facilitate mucus clearance
4. Azithromycin as anti-inflammatory
5. Ibuprofen slows dz progress
72
What are the 3 main types of muscular dystrophy?
1. Duchenne MS
2. Becker
Myotonic Type 1
73
what the 3 MC autosomal trisomies?
1. Down Syndrome (trisomy 21)
2. Edwards Syndrome (trisomy 18)
3. Patau Syndrome (trisomy 13)
74
```
Which autosomal trisomy presents with the following: PRINCE
1. Prominent Occiput
2. Rocker-bottom feet
3. Intellectual disbility
4. Non-disjunction
5. Clenched fist (w/ overlapping fingers)
6. low set Ears
Micrognathia
Congenital Heart dz
Death occurs by age 1
```
Edwards Syndrome
75
Progressive neurodegeneration, developmental delay, cherry red spot on macula, NO hepatomegaly
Tay-sachs
76
What enzyme is deficient in Tay-sach (AR)
Hexosaminidase A
77
What substrate in Accumulated in Tay-sachs
GM2 ganglioside
78
Episodic peripheral neuropathy, angiokeratomas, hypohidrosis (excessive sweating)
Fabry disease
79
What enzyme is deficient in Fabry disease
Alpha-galactosidse A
80
What is accumulated in Fabry disease (XR)
Ceramide trihexoside
81
Central peripheral demyelination with ataxia and edema
Metachromatic leukodystrohy
82
What enzyme is defcient
Arysulfatase A
83
What is accumulated metachromatic leukodystrophy
Cerebroside sulfate
84
What do you expect to see on labs during pregnancy?
Decreased:
1st Trimestor = beta-hcg and PAPP-A
Quad Screen = alpha-fetoprotein, estriol, inhibin A (may be normal)
85
MC cause of Down Syndrome?
Mitotic Non-disjunction
86
In Down Syndrome when does mitotic non-disjunction occur?
Post fertilization
87
What is zellweger syndrome?
1. Autosomal recessive disorder due to mutated PEX
gene
2. Malfunction in peroxisome biogenesis
88
What is the clinical presentation of zellweger syndrome?
1. Hypotonia
2. Hepatomegaly
3. Siezures
4. Early death
89
What is Refsum dz?
1. AR disorder of alpha oxidation
2. inhibit the metabolism of phytonic acid to pristanic
acid
90
How does Refsum dz present?
1. Scaly skin
2. Catarracts --> Night blindness
3. Ataxia
4. Shortening of the 4th toe
5. Epiphyseal dysplasia
91
What is adrenoleukodystrophy?
```
XLR of beta oxidation -->
VLCR (very long chain fatty acid) buildup in:
1. Adrenal glands
2. White (leuko) matter of the brain
3. Testes
```
92
What is the Tx for Refsum dz?
Diet and Plasmapheresis
93
Progressive adrenoleukodystrophy leads to ...
Adrenal gland crisis, coma and death
