Metabolic Diseases Flashcards
(87 cards)
1
Q
6 AMINOACIDOPATHIES
A
Hartnup disease Homocystinuria MSUD Non ketotic hyperglycinemia PKU Sulfide oxidase deficiency
2
Q
Presentation of aminoacidopathies
A
present in infancy or at times of illness with altered mental status, vomiting and poor feeding
3
Q
Ammonia level in aminoacidopathies
A
Usually normal, except in Urea cycle disorders
4
Q
GLYCOGEN STORAGE DISEASES (GSD)
Name the enzyme
I - Von Gierke
A
Glucose-6-phosphatase
5
Q
GLYCOGEN STORAGE DISEASES (GSD)
Name the enzyme
II - Pompe
A
acid maltase (1,4 glucosidase)
6
Q
GLYCOGEN STORAGE DISEASES (GSD)
Name the enzyme
III - Cori-forbes
A
Debranching
7
Q
GLYCOGEN STORAGE DISEASES (GSD)
Name the enzyme
IV - Andersen
A
transglucosidase
8
Q
GLYCOGEN STORAGE DISEASES (GSD)
Name the enzyme
V - McArdle
A
muscle phosphorylase
9
Q
GLYCOGEN STORAGE DISEASES (GSD)
Name the enzyme
VI - Hers
A
liver phosphorylase
10
Q
GLYCOGEN STORAGE DISEASES (GSD)
Name the enzyme
VII - Tarui
A
muscle phosphofructokinase
11
Q
Pattern of inheritance of GSD
A
all are AUTOSOMAL RECESSIVE except
PHOSPHOGLYCERATE KINASE DEFICIENCY (Type IX) which is X-linked
12
Q
Most GSD involve muscle except
A
Type I and VI
13
Q
LYSOSOMAL STORAGE DISEASES
LSD = MPS + NCL + SLD
A
Mucopolysaccharidoses + Neuronal Ceroid Lipofuscinoses + Spingolipidoses
“My Niece Sells LSD”
14
Q
Fabry’s Disease
A
alpha galactosidase
15
Q
Farber’s Disease
A
Ceramidase
16
Q
Gaucher’s Disease
A
Beta glucosidase
17
Q
Krabbe Disease
A
Galactosyl ceramide beta galactosidase
18
Q
Metachromatic Leukodystrophy
A
Arylsulfatase A
19
Q
Niemann Pick Types A and B
A
Spingomyelinase
20
Q
Sandhoff Disease
A
Hexosaminidase A and B deficiency
21
Q
Tay-Sachs Disease
A
Hexosaminidase A deficiency
22
Q
Urea Cycle Disorders
Patients with complete absence of these enzymes present in the ______ period with _____ and _____.
They may have ___________ due to tachypnea.
A
neonatal period
coma and hyperammonemia
respiratory alkalosis
23
Q
T or F
Urea Cycle Disorders
Normal glucose, not acidotic
A
T
24
Q
MC urea cycle defect
A
Ornithine transcarbamylase (OTC) deficiency
25
Inheritance of OTC def
X-linked
the other urea cycle disorders are autosomal recessive
26
Urea Cycle Disorders
```
Carbamyl phosphate synthetase I (CPS I) deficiency
OTC deficiency
Citrullnemia
Arginosuccinicaciduria
Arginemia
```
"Ammonia Came (CPS I) Over The Counter (OTC) synthesized (arginosuccinic acid synthetase), And Slid (Argino-succinic lyase) Away As (arginase) Urea (urea)"
27
Abetalipoproteinemia eponym
Bassen-Kornzweig Syndrome
28
Abetalipoproteinemia cause
mutations in gene that encodes for microsomal triglyceride transfer protein (MTP) on chromosome 4
29
deficiency of MTP results in near absence of apo-B-containing lipoproteins in plasma
Abetalipoproteinemia
30
Abetalipoproteinemia primarily affects ____ columns and ____ tracts
posterior columns and spinocerebellar tracts
31
Clin manifestation of Abetalipoproteinemia
ataxia, neuropathy, streatorrhea, retinitis pigmentosa, acanthocytosis
32
mnemonic
Abetalipoproteinemia is associated with lots of As:
ataxia
areflexia
loss of Vitamin A (and Vitamins D, E, K)
33
mnemonic
Abetalipoproteinemia/ Bassen-Kornzweig disease
BASSEN - K
BASSEN-K
B apolipoprotein B is deficient
Acanthocytosis, ataxia, areflexia, vit A deficiency
Steatorrhea
Sensory loss, Spinocerebellar degeneration
Eye findings: pigmentary retinopathy, Vit E def
Neuropathy
K vit K deficiency
34
Acid Maltase Deficiency
Pompe's Disease or GSD Type II
| autosomal R
35
Infantile Type Acid Maltase Deficiency
| Clinical Manif
neonatal hypotonia
macroglossia
cardiomegaly
hepatomegaly
36
Course/prognosis of Pompe Disease
tend to die by 2 yo from cardioresp failure or aspiration pneumonia without treatment
mnemonic:
patients with infantile onset GSD Type "2" usually die by age "2" yrs without tx
37
Pathologic findings of Pompe
PAS (+) membrane-bound vacuoles in muscle, liver and Schwann cells
38
Pompe Disease
mnemonic
Think of it as Pump's Disease or Plump's Disease
```
Pump's = defective heart (pump)
Plump = plump heart, liver, tongue (cardiomegaly, macroglossia, hepatomegaly)
```
39
Adult Type Acid Maltase Deficiency
| Symptoms
younger adults: fatigue
older adults: leg and trunk weakness
some with respiratory failure
40
Diagnostic Findings in Adult Onset Acid Maltase Deficiency
increased CK
| myotonia on EMG particularly in paraspinal muscles
41
Associated with Adult onset Pompe Disease
Intracranial Aneurysms due to glycogen deposition
42
mnemonic (adult onset Pompe)
| Folks with AM say "I AM what I AM"
Acid Maltase deficiency in adults is associated with Aneurysms and Myopathy (vacuolar) and Asymptomatic Myotonia (in the paraspinal muscles on EMG)
43
Acute Intermittent Porphyria (AIP)
| deficient enzyme
phorphobilinogen deaminase
results in increased production of phorphobilinogen and aminolevulinic acid
glycine + succinyl CoA > aminolevulinic acid > phorphobilinogen (phorphobilinogen deaminase) > hydroxymethylbilane > uroporphyrinogen III >>>> heme
44
AIP
| pattern of inheritance and gene
Autosomal Dominant
| Gene is on 11q
45
AIP
| onset
adolescence and early adulthood
46
AIP attacks triggered by
certain meds, fasting, infection, hormonal changes during pregnancy
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meds avoided in AIP
carbamazepine, clonazepam, phenytoin, valproate
48
Symptoms of AIP
```
motor neuropathy (weakness), may progress to quadriparesis or respi failure, resembling GBS
Decreased reflexes
Confusion, delirium, psychosis, seizures
Severe abdominal pain, fever, tachycardia, HTN
```
49
Problem in Aromatic L-Amino Acid Decarboxylase Deficiency (AADC Deficiency)
autosomal recessive
AADC is impt in synthesis of dopamine and serotonin
Dopa > (AADC) > dopamine
5hydroxytryptophan> (AADC) > serotonin
50
AADC Deficiency mnemonic
AADC
Autonomic symptoms
Athetosis, Ataxia
Dystonia
C (see): ptosis, oculogyric crisis
51
Adrenoleukodystrophy (ALD) lab findings
phytanic acid, pipecolic acid, very long chain fatty acids are elvated
52
Diseases that elevate VLCFA
RAZ (Refsum disease, rhizomelic chondrodysplasia punctata, ALD and Zellweger syndrome), the weak, sickly dog on a Very Long Chain Far Away
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Sx of ALD
dysmorphic, weak, hypotonic
| feed poorly, seizures, hepatomegaly, retinal degeneration, hearing deficit
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Neonatal ALD pattern of inheritance
autosomal recessive
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Sudanophilic Cerebral Sclerosis (ALD)
| pattern of inheritance
X-linked
56
Sudanophilic Cerebral Sclerosis (ALD)
| phenotypes
cerebral form
adrenomyeloneuropathy
addison's disease
asymptomatic
57
Sudanophilic Cerebral Sclerosis (ALD)
| pathology
lame;lar cytoplasmic inclusions in brain and adrenal macrophages, consists of very long chain fatty acid esters
58
Alexander Disease pattern of inheritance
autosomal D
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alexander disease - mutation if gene encoding for ____
GFAP (glial fibrillary acid protein)
60
Sx of Alexander Disease
| mnemonic (Alexander the Great)
megancephaly and seizures
Alexander the Great had a big head /large ego, and seized a lot of land
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MRI in Alexander Disease
demyelination, particularly frontal
| mnenomic; Jason Alexander from Seinfeld has frontal balding
62
2 disease that pathologically involved U fibers
Alexander's and Canavan's
| Alex, Can-U remember the 2 disease that pathologically involved U fibers
63
Pathology in Alexander Disease
| _____ are found in astrocytes of patients
Rosenthal fibers
| Rosenthal fibers are also char of juvenile polycystic astrocytoma
64
Enzyme that converts dopamine to NE
dopamine-B-hydroxylase
65
Sx of Dopamine-B-hydroxylase Deficiency in neonates
hypothermia, hypoglycemia, hypotension
| clue: HYdroxylase
66
Fabry's Disease/Angiokeratoma Corporis Diffusum) pattern of inheritance
X-linked recessive
67
enzyme deficient in Fabry's Disease/Angiokeratoma Corporis Diffusum)
alpha-galactosidase A deficiency
| results in accumulation of glycosphingolipids
68
Often 1st manifestation of Fabry's Disease
Rash
69
Features of Fabry's Disease
Fabry's Disease is associated with All A's
```
Alpha galactosidase A
Acroparesthesias
Autonomic dysfunction
Anhidrosis
Arrhythmia
Acute renal failure
Abdominal pain
```
70
Diseases with Cherry Red Spots
```
(Farber Salivates Getting cherry-picked, half -off Sales at Sacks 5th Ave and Nieman Marcus)
Farber's disease
Sialidosis
GM1 Gangliosidosis
Sandfoff's
Tay Sachs
Niemann Pick Type A
```
71
pathology in Farber's Disease (aka lipogranulomatosis)
ceramidase deficiency
| cause accumulation of ceramide in tissue, particularly joints
72
autosomal recessive degenerative disease that affect gray matter and is accompanied by visceral storage of lipid ceramide
Farber's disease
73
Sx of Farber's disease
hoarseness, subcutaneous nodules, cherry red spots, progressive arthropathy
Neuro: hypotonia, weakness, developemental delay
(Farber and Arthur both like grey ceramic horses = athropathy, grey matter, ceramide, hoarseness)
74
complete deficiency of galactose -1-phosphate uridyltransferase
classical galactosemia
| most severe
75
age at which cataracts develop in galactosemia
1-2 months of age
76
lipid storage disorder due to defect in glucocerebrosidase
Gaucher's disease
| "It may be gauche (Gaucher) but I always have sugar (glucose) on my mind (cerebrum)
77
histiocytes containing lipid (PAS +)
Gaucher cells
78
Types of Gaucher disease
I: non neuropathic, most common
II: acute neuropathic form
(assoc with trismus, strabismus, opisthotonus, spasticity ; death usu by age 2; laryngeal stridor and aspiration pneumonia are common:
III: chronic neuropathic form
(starts at 1st decade; cognitive deterioration, seizures, rigidity, ataxia, horizontal supranuclear gaze palsy; hepatosplenomegaly, ILD)
79
due to mutation in the SLC2A1 gene
GLUT 1 deficiency (De Vivo Disease)
80
Sx of GLUT 1 deficiency
seizures between 1 and 4 months of age; may have apnea and eye movements resembling opsoclonus; delayed milestones, microcephaly, spasticity, ataxia
81
diagnosis of GLUT 1 deficiency
low CSF glucose (<40)
low CSF glucose: serum glucose ratio (1/3)
normal CSF lactate
82
Tx of GLUT 1 deficiency
ketogenic diet
83
MRI shows frontotemporal atrophy with prominent Sylvian fissures; this results in a bat wing appearance
Glutaric Acidemia Type 1
84
may have retinal hemorrhages and subdural effusion
Glutaric Acidemia Type 1
85
deficiency of glutaryl-coenzyme A dehydrogenase
Glutaric Acidemia Type 1
86
lens deviation in Marfan and homocystinuria
Marfan: deviates upward
Homocystinuria: deviates upward
(mnemonic: px with marfan syndrome are really tall, so their lens dislocates upward:
87
If untreated, characterized by Marfanoid features, ectopia lentis and/or myopia, mental retardation, seizures, liveo reticularis, codfish vertebra, malar flush and risk for thrmoboembolism
Homocystinuria due to Cystathione Beta synthase deficiency
