MSK - Genetics - Neurocutaneous, Mitochondrial, & Lysosomal Disorders Flashcards
1
Q
What is the simplified pathophysiology of tuberous sclerosis complex?
A
Mutation in genes coding for tumor suppressor proteins
–> potential mix of benign tumor growth in several organs
(e.g. kidneys, heart, liver, eyes, lungs, and skin)
2
Q
Does tuberous sclerosis typically result in benign or malignant tumors?
A
Benign
3
Q
What are some of the organs most commonly affected by tuberous sclerosis?
A
Skin, brain, kidney, heart, lung
4
Q
85% of individuals with tuberous sclerosis will show a mutation in one of what two genes?
A
TSC2 (69%);
TSC1 (31%)
5
Q
As far as tuberous sclerosis diagnoses go, describe the constellation of signs/symptoms that would indicate each the following in separate patients:
definite TS complex
probable TS complex
possible TS complex
A
Definite
2 major features or 1 major + 2 minor
Probable
1 major + 1 minor
Possible
1 major or 2 minor
6
Q
Between major and minor features of tuberous sclerosis complex, what constellation is needed for definitive diagnosis?
A
2 major features
OR
1 major + 2 minor features
7
Q
Name three skin lesions commonly associated with tuberous sclerosis.
A
Hypomelanotic (ash leaf) macules (87-100% of cases)
Facial angiofibromas (47-90% of cases)
Shagreen (coast of Maine) patches (20-80% of cases)
8
Q
Name two brain lesions commonly associated with tuberous sclerosis.
Name two signs or symptoms of brain lesions commonly associated with tuberous sclerosis.
A
Subependymal nodules (SENs; 90% of cases)
Cortical tubers (70% of cases);
Seizures (80% of cases)
Intellectual Disability (50% of cases)
9
Q
Tuberous sclerosis is associated with mutations in what two genes (85% of cases involving one of these genes)?
What two proteins are coded for by these two genes, respectively?
A
TSC1 - hamartin;
TSC2 - tuberin
10
Q
What is the leading cause of increased morbidity and mortality in tuberous sclerosis?
What is the 2nd leading cause of increased morbidity and mortality in tuberous sclerosis?
A
CNS tumors / intellectual disability;
renal disease
11
Q
What is the most common renal lesion in tuberous sclerosis?
What is the 2nd most common renal lesion in tuberous sclerosis?
A
Benign angiomyolipomas (70% of cases)
epithelial cysts (30% of cases)
12
Q
True/False.
Tuberous sclerosis complex has a fairly high association with autism spectrum disorder?
A
True (~0.4)
13
Q
What mode of inheritance does tuberous sclerosis show?
A
Autosomal dominant
(with variable expressivity)
14
Q
What is the purpose of the proteins hamartin and tuberin?
What disease is associated with mutations in the genes coding for these proteins?
What are the genes?
A
Tumor suppression;
tuberous sclerosis;
TSC1 (hamartin) and TSC2 (tuberin)
15
Q
Name some of the major features of tuberous sclerosis that are present in the majority of cases (bolded).
Name a few features that aren’t necessarily present in the majority of cases (italicized).
A
- Subependymal nodule (SEN) (90%)
- Hypomelanotic (ash leaf) macule (87-100%)
- Facial angiofibroma (47-90%)
- Cortical tuber (70%)
- Shagreen (coast of Maine) patch (connective tissue nevus) (20-80%)
- Cardiac rhabdomyoma (47-67%)
- Renal angiomyolipoma (typically benign)
- Multiple retinal hamartoma
- Lymphangiomyomatosi (LAM) (30%)
- Subependymal Giant Cell Astrocytoma (SEGA) (6-14%)
16
Q
What is a defining feature of tuberous sclerosis autosomal dominant inheritance?
A
Variable expressivity
17
Q
What mode of inheritance does tuberous sclerosis display?
What may be responsible for its variable expressivity?
A
Autosomal dominant;
the ‘two-hit’ hypothesis / random nature of second hit (TSC1, TSC2 genes)
18
Q
True/False.
The majority of cases of tuberous sclerorsis develop malignant renal angiomyolipomas.
A
False (<3%);
70% show benign renal angiomyolipomas
19
Q
Define the medical term proband.
A
An individual who presents with a genetic disorder
(must warrant investigation of the individual’s family)
20
Q
What percentage of tuberous sclerosis probands (new cases) have an affected parent?
What percentage do not?
A
1/3;
2/3 (de novo mutations)
21
Q
An individual with tuberous sclerosis complex has what likelihood of passing it on to their progeny?
(Note: meaning the likelihood of a single birth where one parent is affected resulting in a child with the disease)
A
50%
(autosomal dominant)
22
Q
A child is born with tuberous sclerosis. Neither of her parents are affected. What risk do her future siblings have?
A
1-2%
(possible germline mosaicism)
23
Q
What dermatological lesion is here shown?
With what neurocutaneous disorder is it associated?
A
A shagreen patch;
tuberous sclerosis complex
24
Q
What dermatological lesions are here shown?
With what neurocutaneous disorder is it associated?
A
Hypomelanotic macules;
tuberous sclerosis complex
25
What dermatological lesions are here shown?
With what neurocutaneous disorder is it associated?
Similar wart-like projects and bumps are sometimes associated with this disorder and found where on the body?
Facial angiofibromas;
tuberous sclerosis complex;
skin around nail folds (periungal fibromas)
26
A seven-year-old male is brought in by his concerned parents for your evaluation after experiencing a short seizure of undetermined type and origin.
Upon physical exam, you notice the child has several near-white macules on his hips, back, and shoulders. You also notice some roughened skin on his face in a malar distribution.
The child is mentally disabled.
What syndrome is at the top of your differential?
It is associated with mutations in what gene(s)?
Tuberous sclerosis;
TSC1 (hamartin protein), TSC2 (tuberin protein)
27
What is the treatment for a patient with tuberous sclerosis that has a subependymal giant cell astrocytoma?
What is the treatment for a patient with tuberous sclerosis that has a renal angiomyolipoma?
What is the treatment for a patient with tuberous sclerosis that is experiencing somewhat frequent seizures?
mTOR (mammalian target of rapamycin) inhibitors;
renal artery embolization / surgery (renal sparing);
normal epileptical / seizure control
28
What disorder has a similar pathophysiology as tuberous sclerosis complex (mutations in tumor suppressor genes/proteins) but is mainly characterized by benign tumors of the nervous system?
Neurofibromatosis
29
What are the two types of neurofibromatosis called?
Some sources include what as a third type?
Neurofibromatosis type I and type II;
Schwannomatosis
30
Neurofibromatosis type I is associated with what tumor suppressor gene on what chromosome? What is its inheritance pattern?
Neurofibromatosis type II is associated with what tumor suppressor gene on what chromosome? What is its inheritance pattern?
NF-1, chromosome 17, autosomal dominant;
NF-2, chromosome 22, autosomal dominant
31
Describe the inheritance pattern of both types of neurofibromatosis.
(E.g. inheritance type, expressivity, penetrance, mutation rate)
Autosomal dominant;
nearly 100% penetrant;
high level of variance in expressivity;
high mutation rate (50% of cases are new cases)
32
What is the hallmark feature of neurofibromatosis type I?
What is the hallmark feature of neurofibromatosis type II?
Cafe au lait spoits;
acoustic neuromas
33
What is the hallmark feature of neurofibromatosis type I?
Cafe au lait spots
34
What is the hallmark feature of neurofibromatosis type II?
Acoustic neuromas
35
Why is the diagnosis of neurofibromatosis so difficult?
High variance in expressivity
36
Dianosis of neurofibromatosis type I is made if a person has two or more of what signs and symptoms?
≥ 6 café au lait spots *(\> 5 mm in diameter in pre-pubertal persons and \> 15 mm in post-pubertals)*
≥ 2 neurofibromas of any type
Freckling in the axillary or inguinal regions
Optic glioma
≥ 2 Lisch nodules
A distinct osseous lesion
A first degree relative with NF-1 (by the above criteria)
37
What is the most common CNS tumor of neurofibromatosis type I?
Optic gliomas
38
Chromosome 17 produces a protein that is involved in maintaining the balance between cell proliferation and differentiation.
What protein is it and a deficiency in it is associated what disease?
Neurofibromin;
neurofibromatosis type I
39
Diagnosis of neurofibromatosis type II requires 2 or more of what clinical features?
**Either**
Bilateral auditory canal masses;
**OR**
an affected first-degree relative and a unilateral auditory mass
40
What dermatological lesions are here shown?
This is indicative of what disorder?
It is associated with a mutation of what chromosome?
Cafe au Lait (also known as coast of Maine) spots;
neurofibromatosis type I;
chromosome 17
41
What is the pathophysiology of Huntington's disease?
Neuronal death due to Huntingtin protein amyloidosis
42
What is the genetic cause of Huntington disease pathology?
CAG trinucleotide repeats on chromosome 4
43
Less than how many CAG repeats on chromosome 4 is normal?
Greater than how many CAG repeats on chromosome 4 is associated with severe Huntington's disease?
\< 26;
≥ 40
44
What is the inheritance pattern of Huntington's disease?
It usually presents at what age?
Autosomal dominant'
30 - 40 (can be as low as 10 and as high as 60)
45
The increased severity of Huntington's disease is associated with transmission from which parent?
Paternal transmission
46
Name the major signs and symptoms of Huntington's disease.
Progressive chorea, rigidity, psychiatric symptoms, and dementia
47
What is the most common form of inherited cognitive impairment?
Fragile X syndrome
## Footnote
*(spectrum of ADHD vs. mild impairment vs. autism vs. severe intellectual disability)*
48
What disorder is associated with trinucleotide CGG repeats on the X chromosome?
What number of repeats is considered normal?
What number is considered pathological?
Fragile X syndrome;
5 - 44;
\> 200
49
Fragile X syndrome is generally more severe in which sex?
Males
50
Some cells have 100s of \_\_\_\_\_\_\_\_\_.
Highly active cells can have 1000s of \_\_\_\_\_\_\_\_\_.
Mitochondria;
mitochondria
51
What organelle is the major source of reactive oxygen species (ROSs)?
What organelle regulates apoptosis?
Mitochondria;
mitochondria
52
What is homoplasmy?
What is heteroplasmy?
A cell contains only one type of mtDNA (DNAmitochondrial);
a cell contains both normal and mutant mtDNA
53
What is difficult about the pleiotropic nature of many disorders of the mitochondrial genome?
Different organs can be affected in different patients with the same mutation
54
Disorders of the mitochondrial genome are often pleitotropic and show variable \_\_\_\_\_\_\_\_\_\_\_, making them difficult to both diagnose and also track through generations.
Expressivity
55
**True/False.**
A mutant gene must show effects on multiple phenotypic characteristics simultaneously in order to be considered an example of pleiotropy.
False.
(the same pleiotropic gene can show different effects in differing individuals)
56
If a woman is homoplasmic for a certain mutation, how many of her children are likely to receive that mutation?
If a man is homoplasmic for a certain mutation, how many of his children are likely to receive that mutation?
All of them;
none of them
57
A woman who is heteroplasmic for a point mutation or duplication will pass it on to how many of her children?
(What will the effect be like?)
All of them
(*however*, there will be varying severity of phenotypic manifestation as the fraction of mutant mitochondria in the offspring may vary significantly)
58
A woman who is heteroplasmic for a deletion will pass it on to how many of her children?
(What will the effect be like?)
Likely none of them
(Heteroplasmic deletions are not typically inherited)
59
What are a few factors that contribute to the wide variability in expressivity in disorders of the mitochondrial genome?
Pleiotropy;
heteroplasmy
(fraction of mutant mtDNA among varying individuals and even varying tissues means there is often a whole spectrum of disease manifestation)
60
**True/False.**
The fraction of mutant mtDNA among differing individuals and even differing tissues varies widely, meaning there is often a whole spectrum of disease manifestation.
Yes;
this explains part of the varying expressivity and pleiotropy of disorders of the mitochondrial genome
61
What are two examples of mitochondrial diseases that result from mutations in nuclear DNA?
(1 category and 1 disorder)
Disorders relating to the *POLG* gene (involved in mtDNA replication);
Leigh syndrome (75% of cases;
25% of cases come from deletions of mtDNA)
62
Mutations in the *POLG* gene often have what effect?
A significant drop in mtDNA in affected tissues
63
Describe the clinical manifestations of mitochondrial disorders regarding the following terms:
* Inheritance
* Symptoms
* Organ
* Time
* Scenario
* Diagnostics
* Progression
All extremely variable
(due in part to pleiotropy, heteroplasmy, and variable expressivity)
64
An individual has a significantly low number of mitochondria in each of her cells.
Mutations in what gene may be responsible?
Is there a typical phenotype for this disorder?
*POLG* (nuclear DNA);
no (highly variable)
65
Name five syndromes associated with mutations in mtDNA.
(the first two are acronyms)
(the last one (LS) is *usually* associated with mutations in nuclear DNA)
MELAS;
MERRF;
Kearne-Sayre syndrome;
Pearson syndrome;
Leigh syndrome (although most cases come from mutations in nuclear DNA)
66
MELAS is a disorder that results from mutations in mtDNA.
What does MELAS stand for?
Is it hetero- or homoplasmic?
*(What are some of its signs and symptoms?)*
**M**yopathy, mitochondrial **E**ncephalomyopathy, **L**actic **A**cidosis, and **S**troke-like episodes'
heteroplasmic;
*(weakness, ataxia, headache, seizures, dementia, vomiting, transient hemiparesis, lactic acidosis, deafness)*
67
MERFF is a disorder that results from mutations in mtDNA.
What does MERFF stand for?
Is it hetero- or homoplasmic?
*(What are some of its signs and symptoms?)*
**M**yoclonic **E**pilepsy with **R**agged **R**ed **F**iber;
heteroplasmic;
*(Myopathy, ataxia, sensorineural deafness, dementia)*
68
Kearne-Sayre syndrome is a disorder that results from mutations in mtDNA.
Is it caused by genetic duplications, deletions, or point mutations?
What are some of its signs and symptoms (don't memorize, just be aware of some of these options)?
Deletion;
progressive external ophthalmoplegia of early onset, cardiomyopathy, heart block, ptosis, retinal pigmentation, ataxia, diabetes
69
Pearson's syndrome is caused by what kind of genetic mutations?
What are two of its signs or symptoms?
Deletions in mtDNA;
sideroblactic anemia, exocrine pancreatic dysfunction
70
Leigh's syndrome is caused by what kind of genetic mutations?
What are two of its signs or symptoms?
Deletions in mtDNA;
lesions in the basal ganglia and midline brain stem
71
Kearne-Sayre syndrome, Pearson's syndrome, and Leigh's syndrome are all caused by what sort of genetic mutation?
Deletions in mtDNA
72
How do lysosomal enzymes act upon macromolecules within the lysosome?
In a **step-wise** fashion
(one enzyme after the other in a specific order)
73
**True/False.**
If a single step in the normal lysosomal enzyme step-wise pathway is missing, all subsequent steps will likey not occur.
True.
74
Most lysosomal storage diseases follow what inheritance program?
Autosomal recessive
| (mutations in single enzymes)
75
**True/False.**
Lysosomal storage diseases typically present in newborns.
False;
these are chronically progressive diseases that present with normal newborns
76
What are the five main categories of lysosomal storage disorder?
## Footnote
*(note: they are categories named for the lysosomal substrate involved)*
Mucopolysacharridoses;
sphingolipidoses;
glycogen storage;
glycoproteinoses;
mucolipidoses
(also membrane transporter defects)
77
How do amino acids, carbohydrate monomers, and small lipids leave lysosomes after being digested out of larger structures?
There are many specific transporters in the lysosomal membrane for these building block units
78
What disease is an example of a disorder resulting from lack of a certain amino acid transporter in the lysosomal membrane?
What amino acid is it that cannot leave and crystalizes / builds up in the cell?
What is the result?
Cystinosis;
cystine;
cell death
79
Lamellar, circular lysosomes are associated with what type of disorder?
Sphingolipidoses
80
What are some of the major first signs (in general) of a lysosomal storage disease in terms of noticing something in a child that has met their cognitive and motor milestones?
School failure, regression, seizures
81
Mucopolysaccharidoses involve a failed lysosomal digestion of:
Glycosaminoglycans (GAGs)
82
Name a few major sphingolipidoses.
Tay-Sachs disease;
Gaucher's disease;
Fabry's disease;
Niemann-Pick disease
83
What is the most common form of lysosomal storage disease?
What substance is building up in the lysosome in this condition?
Gaucher disease;
glucocerebroside
84
What organs are most affected in Gaucher disease?
What enzyme is deficient?
Bone, liver, spleen;
glucocerebrosidase
85
The following are all examples of what form of lysosomal storage disease?
Tay-Sachs disease
Gaucher disease
Fabry's disease
Niemann-Pick disease
Sphingolipidoses
86
What are Gaucher cells?
What organs are typically swollen in Gaucher disease?
Lipid-laden macrophages;
liver and spleen
87
A mother brings in her child with hepatosplenomegaly.
Through lab work, lipid-laden macrophages are identified.
What is the likely diagnosis?
Gaucher disease
88
How can lysosomal storage diseases be treated?
**IV infusions of the missing enzyme** every 1-2 weeks
89
What type of disorder results due to a failure of attachment of mannose-6-phosphate to certain enzymes?
To where would M-6-P target these enzymes?
I-cell disease;
lysosomes
90
How does I-cell disease work?
A lack of mannose-6-phosphate means lysosomal enzymes are exocytosed
91
What organ is typically hit first in Fabry disease?
What type of lysosomal storage disease is Fabry disease?
What are the initial symptoms?
The glomeruli;
a sphingolipidosis;
severe rash, proteinuria, corneal whorl clouding
92
What are the general signs seen in mucopolysaccharidoses (a type of lysosomal storage disorder)?
Bone/liver/spleen issues;
coarsening of the face;
corneal clouding
93
What are two examples of a mucopolysaccharidosis with somatic and neurologic effects?
These are a type of:
Hurler's (type I), Hunter's (type II);
lysosomal storage disorder
94
What is an example of a mucopolysaccharidosis with only somatic effects?
What is an example of a mucopolysaccharidosis with only neurologic effects?
These are a type of:
Morquio syndrome (type IV);
Sanfilipo syndrome (type III);
lsosomal storage disease
95
What are a few examples of glycogen storage diseases (a type of lysosomal storage disease)?
von Gierke's disease;
Pompe's disease;
Cori's disease;
McArdle's disease
96
Ataxia telangiectasia is associated with mutations on what gene?
Ataxia telangiectasia is associated with what type of tumor?
Ataxia telangiectasia is associated with a deficiency of what antibody?
XTNR, ATM;
ocular angiomas;
IgA
97
What are the common signs / symptoms of Sturge-Weber syndrome?
(facial, ocular, CNS (x3))
Facial port-wine stains,
glaucoma,
seizures,
intellectual disability,
ipsilateral leptomeningeal angioma
98
Name two lysosomal storage diseases that are X-linked recessive.
Fabry's;
Hunter's
99
What are the major signs of Menke's disease?
Short stature;
white-gray, kinked hair
100
1. One of the commonest LSDs which is inherited in an X-linked fashion is Fabry Disease, which causes proteinuria and renal disease. An unusual presenting feature of Fabry Disease is:
A. mental retardation
B. hepatomegaly
C. pathologic fractures
D. corneal whorl opacification
E. congenital malformations
D. corneal whorl opacification
101
2. A mucopolysaccharidosis condition which manifests with neurologic regression and skeletal signs of storage and hepatosplenomegaly (neurologic + somatic features) in early childhood is \_\_\_\_\_.
A. MPS I (Hurler)
B. MPS III (Sanfilipo)
C. MPS IV (Morquio)
D. Tay-Sachs
E. cystinosis
A. MPS I (Hurler)
102
3. A child is born with stenosis of pharyngeal nostrils (choanal atresia), a coloboma of the iris and and malformations of the ear. The chromosomal evaluation is normal and there are no obvious prenatal or family history features which explain this set of abnormalities. Which of the following is the likely diagnosis?
A. VATER association
B. CHARGE association
C. Maternal PKU effects
D. Fetal alcohol syndrome
E. Oligohydramnios sequence
B. CHARGE association
103
What neurological sequelae are seen in Fabry disease?
None
104
4. In children with inborn errors of metabolism such as isovaleric academia, a metabolic exacerbation leading to acidosis and illness can be caused by which of the following?
A. change in weather
B. intercurrent illness (colds) causing catabolism
C. puberty
D. emotional stressors
B. intercurrent illness (colds) causing catabolism
105
5. Signs of a neurocutaneous disease such as NF1 and tuberous sclerosis include numerous clinical signs. In addition to clinical signs, which of the following is helpful in making a diagnosis of either condition?
A. chromosomal analysis
B. positive family history in a parent
C. microcephaly
D. limb reduction abnormality
B. positive family history in a parent
106
6. Metabolic inherited diseases are often ascertained by newborn screening. The abnormality detected in NBS testing in a newborn with PKU is which of the following?
A. elevated phenylalanine in dried blood spots
B. chromosomal abnormality
C. urine phenylketones
D. elevated fatty acids in dried blood spot
A. elevated phenylalanine in dried blood spots
107
7. In diagnosing a child with disproportional short stature, which of the following tests is most useful?
A. chromosomal analysis
B. urine organic acid analysis
C. complete skeletal series
D. bone marrow biopsy
C. complete skeletal series
108
8. Mitochondrial disorders often do not appear to follow obvious Mendelian inheritance patterns. In conditions such as MELAS, which is the typical inheritance pattern?
A. multifactorial inheritance
B. autosomal dominant with decreased penetrance
C. sporadic inheritance
D. maternal inheritance
D. maternal inheritance
109
9. Diagnosis of neurofibromatosis 1 (NF1) is based on the presence of two or more specific criteria. Which one of the following criteria is NOT included in the NIH Guidelines for clinical diagnosis of NF1?
A. Reduced levels of RAS expression
B. Freckling in the armpit or groin area
C. Two or more neurofibromas
D. Optic glioma
E. Family history of NF1
A. Reduced levels of RAS expression
110
10. 7 year old child is seen by the neurologist because of the combination of multiple café au lait macules, Lisch nodules, and freckling in her armpits and groin. She is MOST at risk for developing:
A. aortic dilatation
B. neurofibromas
C. polycystic kidneys
D. cardiomyopathy
E. neurologic regression
B. neurofibromas
111
11. Which one of the following statements about genetic defects in oxidative phosphorylation is true?
**A.** All genetic defects of oxidative phosphorylation follow an autosomal recessive pattern of inheritance.
**B.** All genetic defects of oxidative phosphorylation follow a maternal pattern of inheritance.
**C.** Genetic defects of oxidative phosphorylation generally affect tissues and organs that rely on glycolysis as the sole energy source (e.g. red blood cells). **D.** Genetic defects of oxidative phosphorylation are due to mutations in the mitochondrial genome in majority of cases.
**E.** Some genetic defects of oxidative phosphorylation follow an autosomal recessive pattern of inheritance and some follow a maternal pattern of inheritance.
**E.** Some genetic defects of oxidative phosphorylation follow an autosomal recessive pattern of inheritance and some follow a maternal pattern of inheritance.
112
A deficiency of the enzyme α-galactosidase A leads to what disease?
Note: copied from Brainscape Step 1 flashcards.
Fabry's disease
113
A deficiency of what enzyme leads to what Fabry's disease?
Note: copied from Brainscape Step 1 flashcards.
α-galactosidase A
114
What type of inheritance does Fabry's disease demonstrate?
Note: copied from Brainscape Step 1 flashcards.
X-linked recessive
115
A patient has peripheral neuropathy of the hands and feet, angiokeratomas of the skin, and both cardiovascular and renal disease.
These characteristics are typical of which lysosomal storage disease?
Note: copied from Brainscape Step 1 flashcards.
Fabry's disease
116
What are some of the main organ systems affected by Fabry's disease?
PNS (peripheral neuropathy of the hands and feet),
skin (angiokeratomas),
heart,
kidneys
117
What substrate accumulates in a patient with a deficiency of α-glucocerebrosidase?
Where?
Note: copied from Brainscape Step 1 flashcards.
Glucocerebroside;
the liver, spleen, and bone (Gaucher's disease)
118
A child has progressive neurodegeneration, developmental delay, cherry-red spots on the macula, and lysosomes with onion skinning; he **does not have hepatomegaly**. These characteristics are typical of which lysosomal storage disease?
Note: copied from Brainscape Step 1 flashcards.
Tay-Sachs disease
(hepatomegaly here would indicate Niemann-Pick)
119
What sign is useful in distinguishing between Tay-Sachs and Niemann Pick?
Hepatomegaly (present in N-P)
120
What enzyme deficiency leads to Gaucher's disease?
α-Glucocerebrosidase
121
What is the most common lysosomal storage disorder?
Gaucher's disease
122
A patient has developmental delay, gargoylism, airway narrowing, and corneal clouding. These characteristics are typical of which lysosomal storage disease?
What is the inheritance pattern?
Hurler's syndrome;
autosomal recessive
123
For which three lysosomal storage disorders are Ashkenazi Jews at an especially increased risk?
Tay-Sachs, Niemann-Pick, and some forms of Gaucher's disease
124
Gaucher's disease inheritance?
Autosomal recessive
125
What are Gaucher cells?
Macrophages that look like crumpled tissue paper on microscopy (they are full of glucocerebroside)
126
Niemann-Pick disease is a deficiency of:
What inheritance pattern does it follow?
Sphingomyelinase;
autosomal recessive
127
A child has progressive neurodegeneration, **hepatosplenomegaly**, and a cherry-red spot on his macula. These characteristics are typical of which lysosomal storage disease?
Note: copied from Brainscape Step 1 flashcards.
Niemann-Pick disease
128
Cherry-red spot on macula **+** hepatosplenomegaly = probably \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
Cherry-red spot on macula **w/o** hepatomegaly = probably \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
Niemann-Pick's disease;
Tay-Sachs disease
129
What type of inheritance does Niemann-Pick disease demonstrate?
Autosomal recessive
130
What enzyme deficiency leads to Tay-Sachs disease?
Hexosaminidase A
131
A deficiency of hexosaminidase A leads to:
Inheritance pattern:
Tay-Sachs disease;
autosomal recessive
132
What enzyme is deficient in Tay-Sachs disease?
What substance accumulates?
Hexosaminidase A;
GM2 ganglioside
133
What two lysosomal storage diseases may present with a cherry-red spot on the macula?
Niemann-Pick disease;
Tay-Sachs disease
134
What substrates accumulates in Hurler's syndrome?
What pattern of inheritance is shown?
Heparan sulfate and dermatan sulfate;
autosomal recessive
135
What substrates accumulates in Hunter's syndrome?
What pattern of inheritance is shown?
Heparan sulfate and dermatan sulfate;
X-linked recessive
136
A patient has mild developmental delay, gargoylism, and airway obstruction but no corneal clouding. These characteristics are typical of which lysosomal storage disease?
Note: copied from Brainscape Step 1 flashcards.
Hunter's syndrome
137
What the two lysosomal storage diseases lead to an accumulation of heparan sulfate and dermatan sulfate?
Hunter's and Hurler's
138
What two lysosomal storage disorders shown an X-linked recessive pattern of inheritance?
Fabry's disease;
Hunter's syndrome
139
What enzyme is deficient in Krabbe's disease?
What substrate accumulates?
What is the inheritance mode?
Galactocerebrosidase;
galactocerebroside;
autosomal recessive
140
Which type of mucopolysaccharidosis shows only somatic symptoms?
Which type of mucopolysaccharidosis shows only neurologic symptoms?
Which types of mucopolysaccharidosis show both neurologic and somatic symptoms?
Morquio's;
Sanfilipo's;
Hunter's and Hurler's
141
Which type of mucopolysaccharidosis shows only somatic symptoms?
(no neurologic)
Marquio's
142
Which types of mucopolysaccharidosis show both neurologic and somatic symptoms?
Hunter's and Hurler's
143
Which type of mucopolysaccharidosis shows only neurologic symptoms?
(no somatic)
Sanfilipo's
