INHERITED METABOLIC DISEASES 2 Flashcards
1
Q
This uncommon disease of the neonatal period or early
infancy has many biochemical etiologies. The symptoms
have consisted of psychomotor regression and episodic
hyperventilation, hypotonia, and convulsions, with intervening periods of normalcy
A
Congenital Lactic Acidosis
2
Q
Pathology of Congenital Lactic Acidosis
necrosis and cavitation of the _______ and ______
A
globus pallidus
and cerebral white matter.
3
Q
Congenital Lactic Acidosis is a variant of what disease?
A
Possibly this is a variant of
Leigh disease.
4
Q
It has
its onset in the neonatal period or early infancy and as a
rule leads to death within a few months. Motor inactivity
and hypotonia, dysmorphic alterations of the skull and
face. What is this?
A
Cerebro h epatorenal (Zel lweger) Disease
5
Q
What is characteristic of Cerebro h epatorenal (Zel lweger) Disease
A
Stippled, irregular calcifications of
the patellae and greater trochanters are highly characteristic .
6
Q
In Zelweger dse:
Pathologically, there is ________of the cerebral cortex
and _______ of white matter as well as a number
of visceral abnormalities-cortical renal cysts, hepatic
fibrosis, intrahepatic biliary dysgenesis, agenesis of
the thymus, and iron storage in the reticuloendothelial
system.
A
dysgenesis
degeneration
7
Q
As to the biochemical abnormality, Moser and
coworkers (1984) demonstrated a fivefold increase of
very-long-chain fatty acids, particularly__________, in the plasma and cultured skin fibroblasts from 35
patients with Zellweger disease.
A
hexacosanoic
acid
8
Q
current notions about the basic abnormality in Zellweger syndrome, namely, that it is caused by a lack of _________ (oxidase-containing, membrane-bound cytoplasmic organelles), in which the very-long-chain fatty acids are normally oxidized
A
liver peroxisomes
9
Q
The most common form of Zellweger syndrome
is due to a mutation in ______ . However, the most
widely recognized peroxisomal disorders are _________ and ______, but the Zellweger
cerebrohepatorenal syndrome can be considered a prototype.
A
PEX1
adrenoleukodystrophy
Refsum disease
10
Q
(OCRL 1 M utati o n )
X-linked recessive,
The abnormal gene is located on chromosome Xq25.26.
A
The Ocu locerebrore n a l ( Lowe) Synd rome
11
Q
Sx of The Ocu locerebrore n a l ( Lowe) Synd rome:
Cause of death is from:
A
Renal failure from RTA
12
Q
In Lowe syndrome:
The primary genetic defects are in the gene encoding ________ of the Golgi complex.
A
inositol
polyphosphate phosphatase
13
Q
sex-linked recessive trait.
The hair is normal at birth but the secondary growth is lusterless and depigmented and feels like steel wool;
A
Menkes disease
14
Q
In Menkes disease
Arteriography discloses tortuosity and elongation of the _______ and _______ and occlusion of some.
The combination of intracerebral hemorrhage and metaphysial bone spurs, which may be
interpreted as “________ has led in some cases
to the erroneous diagnosis of child abuse.
A
corner fractures
15
Q
The manifestations of this disease are attributable
to one of numerous known mutations in a copper transporting _________ resulting in: ________
A
adenosine triphosphatase (ATPase), ATP7 A
failure of Cu absorption
16
Q
Treatment of Menkes disease:
Parenteral administration of cupric salts, usually in
the form of ______ administered subcutaneously
twice daily by the parents, restores the serum and
hepatic copper and may allow normal development in
a few children as noted above but it does not materially
influence the neurologic symptoms
A
copper histidine
17
Q
General features of inherited metabolic disease:
there is a ________ and a paucity of movement without
paralysis or loss of reflexes; later there is _______
A
loss of postural tone
spasticity with
hyperreflexia and Babinski signs.
18
Q
The differentiation of the inherited metabolic diseases
of infancy rests essentially upon four types of data:
1.
2.
3.
4.
A
(1) a few highly characteristic neurologic and ophthalmic
signs;
(2) the presence of an enlarged liver and / or
spleen;
(3) special dysmorphic features of the face; and
(4) the results of several relatively simple laboratory
tests, such as images of the thoracolumbar spine, hips,
and long bones
19
Q
- Acousticomotor obligatory startle: ______
- Abolished tendon reflexes with definite Babinski
signs: _____, _________, _________
A
Tay-Sachs disease
globoid cell (Krabbe) leukodystrophy, occasionally
Leigh disease, and (beyond infancy) metachromatic
leukodystrophy
20
Q
- Peculiar eye movements, pendular nystagmus, and
head rolling: ___________; later, hyperbilirubinemia and Lesch-Nyhan
hyperuricemia (see below) - Marked rigidity, opisthotonos, and tonic spasms:
_______, _______ and _______
(classic triad: trismus, strabismus, opisthotonos)
A
Pelizaeus-Merzbacher disease, Leigh
disease
Krabbe, Alpers disease, or infantile Gaucher disease
21
Q
- Intractable seizures and generalized or multifocal
myoclonus: _________ - Intermittent hyperventilation:___________
lactic acidosis (also nonprogressive familial
agenesis of vermis) - Strabismus, hypotonia, seizures, lipodystrophy:
____________
A
Alpers disease
Leigh disease and congenital
carbohydrate-deficient glycoprotein syndrome
22
Q
- Rapid pendular nystagmus: ___________, rarely Krabbe leukodystrophy, Cockayne syndrome (later age)
- Macular cherry-red spots: __________some cases of infantile NiemannPick disease, and rarely lipofuscinosis
- Corneal opacification: ________, _________; later, the mucopolysaccharidoses
- Cataracts: __________ (also congenital rubella)
A
Pelizaeus-Merzbacher disease,
Tay-Sachs disease and Sandhoff variant,
Lowe disease, infantile GM1 gangliosidosis
galactosemia, Lowe disease, Zellweger
disease
23
Q
- Dysmorphic facies: generalized GM1 gangliosidosis,
________ and ________, and some early
cases of mucopolysaccharidosis and mucolipidosis - Enlarged liver and spleen: ________, _________; one type of hyperarnmonemia; Sandhoff disease; later, the _____________ and mucolipidoses
A
Lowe and Zellweger syndromes
infantile Gaucher disease and Niemarm-Pick disease
mucopolysaccharidoses
24
Q
- Enlarging head without hydrocephalus (macrocephaly):
________ of infancy, some
cases of _______ Alexander disease - Beaking of vertebral bodies in radiographs: ________
(and, at a more advanced age, the mucopolysaccharidoses, fucosidosis, marmosidosis, and
the mucolipidoses)
A
Canavan spongy degeneration
Tay-Sachs disease,
GM1 gangliosidosis
25
5. Multiple arthropathies and raucous dysphonia:
____________
6. Storage granules and vacuolated lymphocytes:
_____________ and __________
Farber disease
Niemarm-Pick disease, generalized 1 gangliosidosis
26
Three aminoacidopathies of the late infantile and
| early childhood period-__________, ________ and _______
PKU, tyrosinemia, and Hartnup
27
One must refer to the phenylketonurias in the plural,
for there are
(1) the usual type and several mild and severe
variants thereof, in all of which _________ is
invariable if the disease is not treated early in life;
(2) other types, presumably allelic mutations, in which there is ________ without PKU and without effect
on the nervous system; and
(3) a rare adult type with a progressive ____________or without neurologic manifestations
mental retardation
hyperphenylalaninemia
spastic paraparesis
28
In PKU, By
5 to 6 years in an untreated child, when the IQ can be estimated,
it is usually less than ________
20, occasionally 20 to 50, and
| exceptionally above 50
29
The majority of PKU patients are _______and fair in
skin and hair color, and their skin is rough and dry and
subject to ________
blue-eyed
eczema.
30
```
A_________ odor (because of phenylacetic
acid excretion) can often be detected
```
musty body
31
The finding of high levels of serum _________(above
| 15 mg/ dL) and of _______ in the blood, CSF, and urine is diagnostic of PKU.
phenylalanine
phenylpyruvic acid
32
screening test for PKU and positive results
Guthrie test (ferric chloride)
33
In Guthrie test
It yields an _______ color that reaches
peak intensity in 3 to 4 min and fades in 20 to 40 min. In
contrast, the __________ color in the urine of patients
with histidinemia is permanent.
emerald-green
green-brown
34
A small number of infants have a variant of PKU in
which a restricted PA diet does not prevent neurologic
involvement. In some such infants, a ______________has appeared as
early as the neonatal period, and, according to Allen and
coworkers, it responds to _________
dystonic extrapyramidal rigidity ("stiff-baby syndrome")
biopterin
35
This i s a rare, predominantly dermatologic arninoacidopathy, but in approximately one-half of the infants there is a mild to moderate degree of mental retardation.
Also, as in some other arninoacidopathies, there may be
self-mutilation and incoordination of limb movements.
H e red ita ry Ty ros i n e m i a ( Oc u l ocuta n e o u s
| Ty ros i n e m i a ; R i c h n e r- H a n h a rt D i sease)
36
In H e red ita ry Ty ros i n e m i a
Palmar and plantar ______ with _______ and
pain are frequently present as a result of an inflammatory
reaction to deposits of crystalline tyrosine (also the cause
of the corneal changes).
keratosis
| hyperhidrosis
37
Hereditary Tyrosinemia
The most severe form (type 1) is caused by a mutation in the gene (FAH) that codes for____________, the final enzymatic step in tyrosine metabolism,
fumarylacetoacetate hydrolase
38
the encephalopathy takes the form mainly of fluctuating
extrapyramidal signs in combination with ocular
and vegetative symptoms
Ty ros i n e Hyd roxy l ase Defi c i e n cy (TH M utati o n )
39
The clinical features consist of an intermittent
red, scaly rash over the face, neck, hands, and legs, resembling that of pellagra. It is often combined with an episodic personality disorder in the form of emotional lability, uncontrolled
temper, and confusional-hallucinatory psychosis;
episodic cerebellar ataxia
H a rt n u p D i s e a s e ( S LC6A 1 9 M utati o n )
40
In Hartnup dse
there is the excretion of large amounts of _______, mainly indoxyl sulfate, particularly after oral L-tryptophan loading, and an abnormally high excretion of nonhydroxylated indole
metabolites.
indicans
41
In Hartnup dse
Treatment consists of avoiding exposure to sunlight
and to ________ drugs. Because of the similarities
between pellagra and Hartnup disease, the usual practice is to give _______in doses of 50 to 300 mg daily
sulfonamide
nicotinamide
42
In Hartnup dse
Possibly a better response
is obtained by the administration of__________in doses of 20 mg/kg tid.
L-tryptophan ethyl
| ester
43
Non Friedrich ataxia:
1. Cerebellar ataxia with diplegia, hypotonia, and mental
retardation (also called____________;
this is a form of cerebral palsy.
2. Agenesis of the cerebellum: early cerebellar ataxia
(with or without mental retardation) and episodic
hyperventilation; this group included the selective
agenesis of the vermis-_________
3. Cerebellar ataxia with cataracts and oligophrenia:
onset from childhood (mainly) to as late as adult
years________________
atonic diplegia of Foerster)
Joubert syndrome.
(Marinesco-Sjogren disease).
44
Non-Friedrich ataxia
4. Familial cerebellar ataxia and retinal degeneration
________
5. Familial cerebellar ataxia with cataracts and ophthalmoplegia or with cataracts and mental as well as
physical retardation.
6. Familial cerebellar ataxia with mydriasis.
(Behr disease).
45
persistent cerebellar ataxias of childhood in
which a metabolic fault or gene defect diseases
```
1.
2.
3.
4.
5.
```
1. Refsum disease
2. Abetalipoproteinemia (Bassen-Kornzweig syndrome)
3. Ataxia-telangiectasia
4. Galactosemia
5. Friedreich ataxia
46
The abnormality is the mutation of the gene for enzyme arylsulfatase A, which prevents the conversion of sulfa tide to cerebroside (a major component of myelin) and results in an accumulation of the former.
Metach ro m atic Leu kodystrop hy ( M LD,
| Arylsu lfatase Deficiency
47
In metachromatic leukodystrophy,
2 Types of mutations:
________ mutation causes a lack of active gene product and of the corresponding enzyme;
___________ mutation results in low levels
0-type
R-type
48
Clinical presentation of metachromatic leukodystrophy
The disease in this age group is characterized clinically
by progressive impairment of motor function (gait disorder,
spasticity) in combination with reduced output of speech
and mental regression
49
IN metachromatic leukodystropy,
The diagnostic laboratory findings, in addition to the
MRI and histologic changes, are the elevated _____________ and a marked_________ and an absence of _________ in white blood cells, in serum, and in cultured fibroblasts
CSF protein (75 to 250 mg/dL)
increase in sulfatide in urine
arylsulfatase A
50
Tx of metachromatic leukodystrophy
Treatment with enzyme replacement or bone marrow
| transplantation is being tried.
51
polymorphism in approximately 7 percent of Europeans and makes the point that low enzyme levels alone are insufficient to be expressed as a phenotype of metachromatic leukodystrophy
"arylsulfatase pseudodeficiency,"
52
AR
psychomotor
deterioration (loss of ability to sit, stand, and
speak), marked hypotonia but brisk reflexes and Babinski
signs, and progressive blindness with optic atrophy but
normal retinae
In neuroaxonal dystrophy
53
In neuroaxonal dystrophy
Pathologic examination reveals ______________ in the posterior columns and nuclei of Goll and Burdach and in the Clarke column, substantia nigra, subthalamic nuclei, central nuclei of brainstem, and cerebral cortex
eosinophilic spheroids
| of swollen axoplasm
54
As stated earlier, Gaucher disease usually develops in
early infancy, but some cases, so-called _________, may begin in childhood, between 3 and 8 years of
age
Gaucher disease
| type III
55
finding of splenomegaly, Gaucher cells,
glucocerebroside storage, and deficient activity of glucocerebrosidase
in leukocytes or cultured fibroblasts
Gaucher Disease
56
a subacute or chronic neurovisceral storage disease with early signs of hepatosplenomegaly and later signs (2 to 4 years) of neurologic involvement.
Late I nfa ntile-Early C h i l d h ood
| N i e m a n n -Pick Disease
57
In Niemann Pick dse
```
progressive dementia, dysarthria, ataxia, rarely
extrapyramidal signs (choreoathetosis), and ________, the latter being a distinguishing feature of the later-onset types
```
paralysis of
| horizontal and vertical gaze
58
Variant of Niemann Pick
characterized by extrapyramidal symptoms and paralysis
of vertical eye movements.
juvenile dystonic lipidosis
59
Variant of Niemann Pick
(liver, spleen, and bone marrow contain histiocytes
with sea-blue granules)-in which there is retardation
in mental and motor development, grayish macular
degeneration, and, in rare cases, posterior column and
pyramidal degeneration
The syndrome of the "sea-blue
| histiocyte"
60
I n type 2 o r so-called juvenile GM1 gangliosidosis, the
onset is between _________months, with survival for 3
to 10 years
12 and 24
61
In Late I nfa ntile-C h i l d hood GM1 G a n g l i osidosis
Important laboratory findings
are hypoplasia of the ____________ bodies,
mild hypoplasia of the _________, and the presence in
the bone marrow of__________ or
wrinkled cytoplasm.
thoracolumbar vertebral
acetabula
histiocytes with clear vacuoles
62
In Late I nfa ntile-C h i l d hood GM1 G a n g l i osidosis
leukocytes and cultured skin fibroblasts
show a deficiency or absence of ___________activity. GM1 ganglioside accumulates in the cerebral neurons.
beta-galactosidase
63
This is a group of diseases in which the storage of lipid in
| neurons is combined with that of polysaccharides in connective tissues
M u copo lysacch a ridoses
64
In MPS,
The nervous system may also be involved secondarily
as a result of skeletal _______ and ____________ of connective tissue at the base of the brain,
leading to obliteration of the subarachnoid space and
obstructive hydrocephalus or compression of the cervical
cord.
deformities and thickening and
| hyperplasia
65
In MPS,
All forms of the disease except the _________
which is sex-linked, are inherited in an autosomal
recessive pattern.
Hunter syndrome,
66
This, the classic form, also known a s _________ , begins clinically toward the end of the first year.
Mental retardation is
severe, and skeletal abnormalities are prominent
MPS 1 OR HURLER'S
67
In Hurler's dse
The biochemical abnormalities consist of the accumulation
of _______ and _________(glycosaminoglycans)
in the tissues and their excretion in the u rine, probably as
a consequence of absence of activity of a-_________
dermatan
heparan sulfate
L-iduronidase.
68
Tx of Hurler
Enzyme replacement therapy
| Hematopoietic stem cell bone marrow transplantation
69
In children with the _________ and those with CNS involvement, bone marrow
transplantation is not helpful and enzyme replacement
is recommended.
milder Scheie
| form
70
Unlike the Hurler and other types, the _________ form
| (MPS II) is transmitted as an X-linked trait
Hunter
71
Hurler and Hunter syndromes are clinically alike except that the ________ form is milder:
mental retardation is less severe
than in the Hurler type, deafness is less common, and
corneal clouding is usually absent
Hunter
72
This form, o r MPS III, expresses itself clinically between 2
and 3 years of age, with progressive intellectual deterioration.
The patients are of short stature, but in other respects
the physical changes are fewer and less severe than in the Hunter and Hurler syndromes
S a nfi l i p p o D i sease
73
This form o f the disease, MPS rv; i s characterized by
| marked dwarfism and osteoporosis
Morqiuo dse
74
Features of Morquio
Skeletal deformity and compression of the spinal cord and medulla are constant threats because of_______ and atlantoaxial dislocation and ________around the cervical cord and inferior surface of the cerebellum.
hypoplasia of the odontoid process
thickening of the dura
75
There is excessive excretion of derma tan and heparan
| sulfate, the result of a deficiency of B-glucuronidase
MPS 7 OR SLY DSE
76
the morphologic features are those of
gargoylism, with slowly progressive mental retardation.
Cherry-red spots in the maculae, corneal opacities, and
ataxia have been noted in some patients
mucolipidosis I
77
the most common of the mucolipidoses,
Abnormal facies and periosteal thickening (dysostosis m ultiplex, like that of GM1 gangliosidosis and Hurler disease) are characteristic.
mucolipidosis II (I-cell disease)
78
symptoms do not appear until 2 years of age or later
and are relatively mild. Retardation of growth, fine corneal
opacities, and valvular heart disease are the major
manifestations.
m ucolipidosis III (pseudo-Hurler polydystrophy
79
dysmorphic features of broad nose, depressed bridge, thick lips, and protruding tongue.
M a n n os i d os i s
80
M a n n os i d os i s
Mannosiduria is diagnostic, caused by a defect
in __________. Mannose-containing oligosaccharides
accumulate in nerve cells, spleen, liver, and leukocytes
alpha-mannosidase
81
a. Corneal clouding---several of the mucopolysaccharidoses
like ______, _________, _______ mucolipidoses, tyrosinemia, aspartylglycosaminuria
(rare)
```
b. ____________-GMZ gangliosidosis,
GM1 gangliosidosis (half the cases), lipomucopolysaccharidosis,
occasionally Niemann-Pick disease
```
c. ____________________Jansky-
Bielschowsky lipid storage disease, GM1
gangliosidosis, syndrome of sea-blue histiocytes
(Hurler, Scheie, Morquio, Maroteaux-Lamy),
Cherry-red macular spot
Retinal degeneration with pigmentary deposits
82
d. Optic atrophy and blindness-__________ and __________
e. _______________Marinesco-Sjogren syndrome, Fabry
disease, mannosidosis
f. Ocular apraxia-ataxia-telangiectasia, NiemannPick
disease
g. ____________late infantile
Niemann-Pick disease, juvenile dystonic lipidosis,
sea-blue histiocyte syndrome, Wilson disease
h. _____________ limited abduction-late
infantile Gaucher disease
metachromatic leukodystrophy, neuroaxonal dystrophy
Cataracts
Impairment of vertical eye movements-
Jerky eye movements,
83
_____________-late-onset Niemann-Pick disease
(rigidity, abnormal postures), juvenile dystonic
lipidosis (dystonia, choreoathetosis), Rett, ataxiatelangiectasia
(athetosis), Sanfilippo mucopolysaccharidosis,
type I glutaric acidemia, Wilson disease,
Segawa dopa-responsive dystonia
Extrapyramidal signs
84
___________Hurler, Scheie, Morquio,
and Maroteaux-Lamy forms of mucopolysaccharidosis,
aspartylglycosaminuria, mucolipidoses, GM1
gangliosidosis, mannosidosis, fucosidosis (some
cases), multisulfatase deficiencies (Austin), some
mitochondrial disorders
Facial dysmorphism-
85
__________Hurler,
Morquio, and other mucopolysaccharidoses,
Cockayne syndrome
Dwarfism, spine deformities, arthropathies
86
______________-Niemann-Pick disease,
Gaucher disease, all mucopolysaccharidoses, fucosidosis,
mucolipidoses, GM1 gangliosidosis
Enlarged liver and spleen
87
__________(Cockayne syndrome
and one form of porphyria);
___________ (Fabry disease, fucosidosis);
telangiectasia of ears, conjunctiva, chest (ataxia-telangiectasia);
_______(Sjogren-Larsen disease, caused by
fatty alcohol dehydrogenase deficiency);
plaque-like lesions in _________
photosensitivity
papular nevi and angiokeratoma
ichthyosis
Hunter syndrome
88
__________mucopolysaccharidoses, mannosidosis,
Cockayne syndrome
10. _________mucolipidoses, mannosidosis
11. ____________all mucopolysaccharidoses,
mucolipidoses, mannosidosis, fucosidosis
12. __________-all mucopolysaccharidoses,
mucolipidoses, mannosidosis, fucosidosis, multiple
sulfatase deficiencies
Deafness-
Hypertrophied gurns-
Vacuolated lymphocytes-
Granules in neutrophils
89
Of the other cerebellar ataxias of late childhood and adolescence, only the
1
2
3
4
5
fall into the category of truly metabolic disease
```
BassenKornzweig acanthocytosis,
late-onset G M2 gangliosidosis,
Refsum disease,
ataxia-telangiectasia,
and a genetic fault in vitamin E metabolism
```
90
____________ is a prominent feature
of Unverricht-Lundborg (Baltic) disease and Lafora-body
disease
Cerebellar ataxia
91
In____________ , spastic weakness and pseudobulbar palsy are combined
with cerebellar ataxia
cerebrotendinous xanthomatosis
92
__________ children have
a broad-based gait and are clumsy in addition to being
obese, genitally deficient, and diabetic
Prader-Willi
93
a rare metabolic disease of lipoproteins that causes ataxia, sensory neuropathy, and acanthocytic deformity of red cells
B a sse n - Ko r n zw e i g Aca nth ocytosis
| Abeta l i po p rote i n e m i a
94
Vitamin deficiency associated with Bassen Acanthocytosis
Vit E
95
___________, in which progressive
muscular atrophy, seizures, involuntary movements,
and elevated serum creatine kinase (CK) are
combined in various configurations
McLeod syndrome
96
This is another rare but well-defined disease resembling
abetalipoproteinemia, in which there is hypocholesterolemia,
acanthocytosis of red blood corpuscles, retinitis
pigmentosa, and a pallidal atrophy (HARP syndrome) .
Fa m i l i a l H y p o beta l i po p rote i n e m i a
97
widespread, continuous myoclonus (except during
deep sleep) affecting male and female infants whose
development had been normal until the onset of the
disease at the age of 9 to 20 months
Myoclonic Enceph of Infants/ Opsoclonus-Myoclonus syndrome
98
Treatment of Myoclonic Enceph of Infants/ Opsoclonus-Myoclonus syndrome:
___________ in doses of 1.5 to 4.0 mg/ d
suppresses the myoclonus and permits developmental
progress
Ordinary___________ seem to have no effect.
Dexamethasone
anticonvulsants
99
F a m i l i a l Prog ress ive Myoc l o n u s
Five major categories o f familial polymyoclonus of
late childhood and adolescence have been delineated:
1
2
3
4
5`
( 1 ) Lafora- or amyloid-body type, (2) juvenile cerebraretinal
degeneration, (3) cherry-red spot myoclonus
(sialidosis or a-neuraminidase deficiency), (4) mitochondrial
encephalopathy, and (5) a more benign degenerative
disease (dyssynergia cerebellaris myoclonica of
Hunt) .
100
polyglucosan bodies in the dentate, brainstem, and thalamic neurons
The myoclonus becomes widespread and can be evoked as a startle by noise, an unexpected tactile stimulus (even the tap of a reflex hammer), and also by excitement, or certain sustained motor activities
Lafora-Body Polymyoclonus With Epilepsy
101
EEG of Lafora
The EEG shows diffuse slow waves and
| spikes as well as bursts of focal or multifocal discharges
102
HP of Lafora
Neuropathologic examinations have shown a slight loss
of granule and Purkinje cells and loss of neurons in the
dentate nuclei, inner segment of globus pallidus, and
cerebral cortex in addition to the Lafora bodies
103
ceruloplasmin, the serum protein that binds copper,
is reduced in this disease
recession of symptoms
after prolonged treatment with BAL
Hepalenticular degeneration/ Wilson's dse
104
In Wilson's dse:
The gene, called ATP7B (homologous
with the ATP7 A gene, which is defective in Menkes
disease), codes for a membrane-bound, _________
copper-binding
| ATPase
105
In Wilson's dse
The mutation gives rise to two fundamental disturbances
of copper metabolism:
1.
2.
(1) a reduced rate of incorporation
of copper into ceruloplasmin and (2) a reduction
in biliary excretion of copper
106
In Wilsons
The first neurologic manifestations are most often
_________ with a proclivity to affect the oropharyngeal
musculature.
extrapyramidal
107
dysphagia and drooling, rigidity and slowness
| of movements of the limbs; flexed limb postures, "vacuous smile"; dysarthria or virtual anarthria
Wilson's dse
108
In Wilson's:
They take the form of a crescentic rusty-brown discoloration of the deepest layer of the cornea (Descemet membrane).
KF rings
109
T or F,
In Wilsons
In the purely hepatic stage of the disease,
the rings may not be evident (in 25 percent of cases), but
they are virtually always present (if properly sought) once the neurologic signs become manifest
T
110
Dx of Wilsons
low serum ________ level (less than 20 mg/ dL in 80 to 90 percent of patients),
low serum _________ (3 to 10 mM/L; normal ll to
24 mM/L), and
increased urinary copper excretion (more
than 100 mg Cu/24 h) corroborate the diagnosis
ceruloplasmin
copper
111
In Wilsons
Early
in the course of the illness, the most reliable diagnostic
findings are a _______________ (more than 200 f/-g Cu/ g dry weight) and a failure
to incorporate ________
high copper content in a biopsy of liverc tissue
labeled 64Cu into ceruloplasmin
112
T or F
Persistent
aminoaciduria, reflecting a renal tubular abnormality, is
present in most but not all patients.
T
113
MRI of Wilsons
also an increase in T1 signal throughout the basal
ganglia, particularly in the __________
pallidum
114
HP of Wilsons
in the rapidly
advancing and fatal form, there is frank cavitation in the
____________
lenticular (putamina! and pallidal) nuclei,
115
In Wilsons
marked hyperplasia
of protoplasmic astrocytes ____________in
the cerebral cortex, basal ganglia, brainstem nuclei, and
cerebellum, almost certainly a reaction to liver failure and
hyperarnmonemia.
(Alzheimer type II cells)
116
Tx of Wilsons
reduction of
dietary copper to less than ________ which can usually
be accomplished by avoidance of copper-rich foods
1 mg/d,
117
Tx of Wilsons
administration of the copper chelating agent
D_________ by mouth, in divided doses.
___________ should be added in order to prevent
anemia.
-penicillamine (1 to 3 g/d)
Pyridoxine 25 mg/ d
118
adverse reactions with penicillamine
(lupus-like or nephrotic
| syndromes or myasthenia gravis
119
alternative for penicillamine
triethylene
| tetramine (trientine) or ammonium tetrathiomolybdate
120
___________ which blocks the intestinal
absorption of copper, is also a suitable treatment, but
ineffective alone
Zinc,
121
T or F
institution of treatment
with penicillamine may induce an abrupt remission of
neurologic signs
F
| worsening
122
An important aspect of treatment is the screening of
potentially affected relatives for abnormalities of serum
copper and ceruloplasmin; if any relative is found to
have the disease, penicillamine should be given _____________to prevent the emergence of neurologic symptoms
indefinitely
123
This is a rare illness, similar t o Wilson disease, occurring
in patients with a recessively inherited deficiency of ceruloplasmin;
it is not simply a heterozygous form of Wilson
disease (the mutation involves a different gene).
H e red ita ry Defi c i e n cy of C e r u l o p l as m i n
| Ac e r u l o p l a s m i n e m i a , C P M utati o n
124
also
| known as pigmentary degeneration of the globus pallidus.
N e u ro d e g e n e rati o n With B ra i n I ro n
| Acc u m u l at i o n ( Fo r m e r l y, H a l l e rv o r d e n - S patz D i sease, PA N K M utati o n )
125
In Hallervorden-Spatz dse,
caused by, in all classic cases, a defect in the gene encoding ____________ usually in the form of a missense
mutation.
pantothenate kinase 2 (PANK2),
126
In Hallervorden-Spatz dse,
there is increased uptake of radioactive
iron in the region of the __________ following intravenous injection of labeled ferrous citrate
basal ganglia
127
In Hallervorden-Spatz dse,
In T2-weighted images, the rim of
the pallidum appears intensely black (iron deposition),
with a small white area in its medial part that represents
a zone of __________
necrosis
128
MRI
"eye-of-the-tiger
In Hallervorden-Spatz dse,
129
In Hallervorden-Spatz dse,
T or F
Tx is Levo-dopa
F
No TX
130
it is a hereditary choreoathetosis with self-mutilation and
| hyperuricemia
Lesc h - N yh a n Sy n d ro m e ( H P RT 1 M utati o n )
131
In Lesch Nyhan Syndrome
A deficiency of the enzyme ______________ has been found in all typical cases of this disease
hypoxanthine guaninephosphoribosyl transferase (HPRT)
132
In Lesch Nyhan Syndrome
This is with the xanthine oxidase inhibitor
allopurinol, which blocks the last steps of uric acid
synthesis, reduces the uric acid in Lesch-Nyhan disease,
and prevents the _________, but it seems to
have no effect on CNS symptoms
uricosuric nephropathy
133
In Lesch Nyhan Syndrome
_______ is reported to have suppressed the self-mutilation after haloperidol (Haldol) had failed to do so.
Fluphenazine
| Prolixin
134
This is an idiopathic form of calcification of
the basal ganglia and cerebellum in which choreoathetosis
and rigidity are prominent acquired features
Fahr's dse
135
T or F,
In Fahr's dse
The serum calcium levels in the aforementioned
diseases are usually normal and there is no explanation
of the calcification
T
136
The terms ________, ________ , ________
etc., refer to the distinctive products of myelin degeneration and staining characteristics (or lack thereof) of the white matter in the individual leukodystrophies
metachromatic, sudanophilic, orthochromic,
137
The fundamental defect is impairment in peroxisomal
oxidation of very-long-chain fatty acids (VLCFAs), leading
to their accumulation in the brain and adrenal glands
Ad renoleu kodystrop hy ( S u d a n o p h i l i c
| Leu kodystrophy, ABCD 1 M utati o n }
138
Ad renoleu kodystrop hy (ALD)
```
The deficient membrane protein, encoded by
a gene that maps to chromosome_________, is a peroxisomal
membrane transporter (ABCD1
```
X28
139
Subtypes of ALD
1.__________________-the
classic type, accounting for half of all cases
```
2. An intermediate form in juvenile or young adult
males with______________involvement (5 percent
of cases)
3. A progressive ________________ in adult
males (25 percent of cases)
```
A progressive degeneration of cerebral white matter
in young males, often with cortical blindness
cerebral and spinal
spinal cord tract degeneration
140
Subtypes of ALD
4. A chronic mild, nonprogressive spastic paraparesis in
______________ carriers (10 percent of cases)
5. Familial instances of ___________ without neurologic
involvement in males (10 percent of cases)
6. Possibly, in male infants, a form originating at birth
____________
heterozygous female
Addison disease
(e.g., Zellweger disease)
141
Lab dx of ALD
The specific laboratory marker of the disease is an excess of VLCFAs, in particular three measurements are of value:
the absolute level of
__________, the ratio of C26 to C22 (docosahexanoic
acid; C26:C22), and of C24 (tetracosanoic acid)
to docosahexanoic acid (C24:C22) in plasma, erythrocytes,
leukocytes, or cultured fibroblasts
hexacosanoic acid (C26)
142
metabolic diseases associated with stroke
homocystinuria, Fabry
disease, and sulfite oxidase deficiency,
Tangier disease and familial hypercholesterolemia.
143
This aminoaciduria i s inherited a s an autosomal recessive
| trait and simulates Marfan disease
H o m ocyst i n u ri a
144
In Homocyinuria,
The only neurologic abnormality is ________usually
of mild degree, which sets this syndrome apart from
Marfan disease, in which intellect is unimpaired
mental retardation,
145
T or F
In Homocyinuria,
Blood vessel changes of thickening and fibrosis of the
coronary, cerebral, and renal arteries tend to appear later
in the illness.
T
146
In Homocystinuria,
Homocysteine is elevated in the blood and CSF, and
homocystine in the urine. This is because of an inherited
____________ that results in an inadequacy of cystathionine formation, a substance essential
to many tissues including the brain
cystathionine synthase deficiency
147
In Homocystinuria,
The administration of large doses (50 to 500 mg) of
_________ (a cystathionine synthase coenzyme), ______
5 mg daily and ______ (vitamin B12) 1,000 !lg daily,
reduces the excretion of homocystine
pyridoxine
folate
cobalamin
148
This disease, also known as angiokeratoma corporis diffusum, is inherited as an X-linked recessive tra
Fa b ry D i sease (An d e rso n-Fa b ry D i sease, G LA
| M utat i o n ) (
149
The primary deficit is in the enzyme
___________, the result of which is the accumulation of ceramide trihexoside in endothelial, perithelial, and smooth muscle cells of blood vessels as well as in renal tubular and glomerular cells and other viscera and in nerve cells in many parts of the nervous system
alpha-galactosidase A
150
There was an increased level of sulfite and
thiosulfate and an abnormal amino acid, 5-sulfocysteine,
in the blood.
S u l fite O x i d a s e Defi c i e n cy
151
the histochemical and electron-microscopic abnormalities of the muscle mitochondria in a childhood myopathy; which they called _____________(meaning marked enlargement of the mitochondria)
or _________(referring to an excessive number
of mitochondria)
megaconial
pleoconial
152
so named because of the subsarcolemmal
and intermyofibrillar collections of membranous mitochondrial) material in the type 1 (red) muscle fibers
as visualized by the Gomori trichrome stain in sections
of frozen muscle
"ragged red fibers,"
153
A second unifying feature of mitochondrial diseases is an
elevation of __________or of the ___________
ratio in the blood and CSF; this is the result of
the respiratory chain abnormalities.
lactate concentration
lactate-to pyruvate
154
________and ________ particularly have a tendency to
exhibit elevations of lactate; however, the diagnosis of
either cannot be excluded in the presence of normal levels of this substance, even after provocation by exercise
Leigh syndrome
MELAS
155
________a symmetrical subacute
necrotizing encephalomyelopathy; usually with
lactic acidosis,
Leigh syndrome,
