Biochemistry Diseases Flashcards
1
Q
Von Gierke’s disease
A
5 month old patient comes in with severe hypoglycemia, massive liver enlargement, failure to thrive, ketosis, hyperuricemia and increased concentrations of ketone bodies, lactic acid, pyruvate
Glycogen: normal structure, increased amount in the liver
2
Q
Glucose 6 phosphatase deficiency
A
Von Gierke’s disease enzyme deficiency
3
Q
Pompe’s disease
A
cardio-respiratory failure, death before age 2
Glycogen: normal structure; massive increase in the amount of glycogen in the heart
4
Q
Alpha-1,4-glucosidase deficiency
A
Pompe’s disease enzyme deficiency
5
Q
Cori’s disease
A
mild hypoglycemia, liver enlargement, buildup of keto-acids, lactic acid and pyruvate
Glycogen: increased amount with short outer branches
6
Q
Limit dextrans
A
glycogen with small outer branches
7
Q
Debranching enzyme deficiency
A
Cori’s disease enzyme deficiency
8
Q
Andersen’s disease
A
Progressive liver cirrhosis, liver failure
Glycogen: normal amount with very long outer branches
9
Q
Branching enzyme deficiency
A
Andersen’s disease enzyme deficiency
10
Q
McArdle’s disease
A
Patient presents with limited ability to exercise, have painful muscle cramps and no increase in lactic acid levels after a stress test
Glycogen: moderately increased amount with normal structure
11
Q
Muscle glycogen phosphorylase deficiency
A
McArdle’s disease enzyme deficiency
12
Q
Her’s disease
A
mild hypoglycemia and hepatomegaly, adaptable
Glycogen: increased amount in the liver with normal structure
13
Q
Hepatic glycogen phosphorylase deficiency
A
Her’s disease enzyme deficiency
14
Q
Muscle Phosphofructokinase deficiency
A
limited ability to exercise, painful cramps
Glycogen: normal but reduced ability to utilize it
15
Q
Essential fructosuria
A
Fructose in the urine
16
Q
Fructokinase deficiency
A
Essential fructosuria
17
Q
Hereditary Fructose Intolerance
A
~5 month old Infant presents with severe vomiting, poor feeding, jaundice, failure to thrive, later develop cataracts and cirrhosis
18
Q
Aldolase B deficiency
A
Hereditary fructose intolerance, accumulation of fructose-1-phosphate
19
Q
Excessive fructose intake
A
See obesity due to no regulation of glycolysis leading to increased LDL which leads to increased fat in the body
20
Q
Classic Galactosemia
A
Neonates present with vomiting and diarrhea following milk ingestion, also see failure to thrive and mental retardation, cirrhosis and cataracts develop later, deficiency in Galactose-1-phophate uridyl transferase OR galactokinase
21
Q
Galactose-1-Phosphate Uridyl Transferase Deficiency
A
Classic Galactosemia enzyme deficiency
22
Q
Galactosemia triad
A
Mental retardation, cirrhosis and cataracts
23
Q
Sorbitol Dehydrogenase deficiency
A
Known non-diabetic patient presents with cataracts in the lens, retinopathy (bilateral) and neuropathy
24
Q
Glucose-6-Dehydrogenase deficiency Type A
A
African patient presents with self-limiting episodes of hemolytic anemia after exposure to oxidant drugs, specifically antimalarials, sulfonamides, nitrofurantoins), infections (hepatitis, pneumonia, typhoid fever)
25
Glucose-6-Dehydrogenase deficiency
Middle eastern patient presents with hemolytic anemia after exposure to oxidant drugs (antimalarials, sulfonamides, nitrofurantoins) infections (hepatitis, pneumonia and typhoid fever) or fava bean ingestion
26
Hurler's disease
Patient presents with corneal clouding, dystosis multiplex, organomegaly, heart disease, dwarfism, mental retardation, genetic testing shows it is an autosomal recessive disorder and you suspect early mortality for your patient
27
Hunter's disease
Patient presents with dystosis multiplex, organomegaly, heart disease, dwarfism, mental retardation, genetic testing shows it is an X-linked recessive disorder and you suspect early mortality for your patient
28
I-cell disease
Patient prevents with severe psychomotor retardation, skeletal abnormalities, coarse facial features and show painful and restricted join movement, also likely have early mortality
29
GlcNAc Phosphotransferase Deficiency
I-Cell disease enzyme deficiency --> lysosomes appear in fibroblasts as inclusion bodies
30
Chronic Pancreatitis
Patient presents with steatorrhea, testing shows they cannot break down lipids for uptake into their cells, see decreased levels of lipase
31
Cirrhosis
Patient presents with steatorrhea, testing shows an inability to form micelles, excrete all taken in lipids due to decreased amount of intraduodenal bile acids
32
Celiac sprue
Patient presents with steatorrhea due to an inability to uptake lipids and reesterify them for export to the rest of the body due to mucosal dysfunction
33
Abetalipoproteinemia
Patient presents with steatorrhea, testing shows a lack of betalipoproteins and an inability to form chylomicrons
34
Intestinal lymphangiectasia
Patient presents with steatorrhea, testing shows a abnormal lymphatics
35
Carnitine Deficiency
patient presents with mild muscle cramps that can be severe, you suspect they could lead to death because the patient cannot perform beta-oxidation
36
Carnitinepalmitoyltransferase Deficiency Type I
patient prevents with severe hypoglycemia and coma, you suspect they will die soon and further testing shows that they have reduced fatty acid oxidation and ketogenesis
37
Carnitinepalmitoyltransferase deficiency Type II
patient presents with muscle pain, myglobinuria after exercise, and severe weakness, you suspect rhabdomylosis also and testing shows reduced fatty acid oxidation and ketogenesis in muscle cells
38
Acyl-CoA dehydrogenase deficiency
Patient presents with an intolerance to fast, recurrenty hypoglycemic coma, further testing shows MC/VLC/LC/SC-dicarboxylicaciduria, low plasma and tissue carnitine and you suspect impaired ketogenesis and impaired beta-oxidation
39
Refsum Disease
Patient presents with peripheral neuropathy, cerebellar ataxia, retinitis pigmentosa and complain of skin changes (bone changes), you suspect it is due to accumulation of phytanic acid due to an autosomal recessive disorder
40
PhytanoylCoA hydroxylase deficiency
Refsum disease enzyme deficiency
41
Paroxysmal Nocturnal Hemoglobinuria
Patient presents with venous thrombosis, hemolytic anemia and a history of passing red urine in the morning that gets lighter through the day, you also suspect deficient hematopoesis
42
Phophatidylinositolglycan A mutation
Paroxysmal Nocturnal hemoglobinuria cause, see failed complement activation prevention
43
Niemann Pick disease
Infant approx 6 months old presents with a protuberant abdomen (you suspect hepatosplenomegaly), progressive failure to thrive, vomiting, fever and generalized lymphadenopathy, parent also reports progressive deterioration of psychomotor function, further testing shows foaminess in the cytoplasm of CNS cells
44
Sphingomyelinase Deficiency
Niemann Pick disease -- accumulation of sphingomyelin in cells
45
Krabbe Disease
Accumulation of Galactocerebrosides
46
Gaucher's disease
Patient presents with pain, fatigue, jaundice, bone damage, anemia and you suspect death is imminent, further examination shows hepatosplenomegaly, osteoporosis and marrow analysis shows cells replaced with fibrillary cells, you suspect a autosomal recessive disorder
47
Gaucher's cells
phagocytic cells have a cytoplasm that is fibrillary like a crumpled tissue paper
48
Glucocerebrosidase deficiency
Gaucher's disease --> accumulation of glucocerebroside (liver, spleen, bone marrow)
49
Sulfatidelipidosis
Accumulation of sulfatides, AKA: metachromaticleukodystrophy
50
Fabry's disease
Accumulation of globotrioscycleramide (primarily in the kidneys)
51
Tay-Sach's disease
6-month old infant presents with progressive mental and motor deterioration, eventually develop muscular flaccidity, blindness and increasing dementia, you suspect they have a genetic mutation on chromosome 15 and will reach a vegetative state by 1-2 years and likely die by age 3, further examination confirms your diagnosis as you see a cherry-red spot on the retina
52
Cholelithiasis
Decreased bile acids cause increased biliary cholesterol excretion and a build up of cholesterol in the gall bladder
53
21-hydroxylase deficiency
female patient presents with salt wasting, virilization and ambiguous genitalia, you suspect congenital adrenal hyperplasia, further testing shows a lack of aldosterone and cortisol and increased testosterone levels
54
11-beta hydroxylase deficiency
Patient presents with hypertension, physical examination shows virilization, further testing shows increased levels of 11-deoxycortisol, and excessive androgen production
55
17-alpha hydroxylase deficiency
Patient presents with hypertension, further examination shows hypokalemia and excessive levels of mineralocorticoids and a failure of pubertal development in genetic females, genetic males present with female external genitalia and intra-abdominal testes
56
3-beta hydroxyl steroid dehydrogenase deficiency
Patient presents with adrenal failure in early infancy, further testing shows defective production of steroids
57
PEM Kwashiorkor
Patient presents muscle wasting, edema and a distended abdomen, have a history of a low protein/absent protein diet
58
Deficiency of dietary protein
PEM Kwashiorkor disease
| decreased albumin levels lead to decreased osmotic pressure
59
Chronic Granulomatus Disease
NADPH oxidase deficiency, suffer from repeated infections (commonly from Staphylococcus Aureus)
60
Linoleic acid deficiency
Results in lack of arachidonic acid, which leads to poor growth, poor wound healing and dermatitis
61
Hyperlipoproteinemia Type I: Lipoprotein Lipase deficiency
Patient presents with pancreatitis and high circulating levels of chylomicrons
62
Type II Hyperlipoproteinemia: Familial Hypercholesterolemia
Patient presents with symptoms of a MI and blood work shows high LDL levels, you suspect a receptor is missing
63
Type III Hyperlipoproteinemia: Familial Dysbetalipoproteinemia
Patient presents with symptoms of MI, blood work shows high LDL levels and no circulating ApoE is found
64
Folate Deficiency
See increased levels if FiGlu in the urine
65
Histidinemia
You do a patients regular check up blood work and notice high levels of histidine and very low levels of urocanic acid, you suspect an amino acid metabolism disorder
66
Propionyl CoA carboxylase deficiency
Patient presents with episodic vomitting, lethargy, ketosis, developmental retardation, intolerance to protein and hyperglycinemia and hyperglycinuria (AKA: Ketotic Hyperglycinemia)
67
Methyl malonic aciduria
Patient presents with developmental retardation and chronic metabolic acidosis, you suspect an amino acid metabolism disorder and treat with B12 supplements but there is no improvement in the symptoms
68
Classic Maple Syrup Urine Disease
A 12 hour old infant is brought into the ER with poor feeding and irritability and you notice a maple syrup odor, further blood work shows ketonuria
69
Maple Syrup Urine Disease Enzyme Deficiency
Branched-Chain ketoacid dehydrogenase
70
Intermediate Maple Syrup Urine Disease
10 year old comes to your office and the mother complains of a maple-syrup like odor, tells you that the child has not been eating well, is irritable and lethargic, you suspect an amino acid metabolism disorder with residual enzyme activity
71
Intermittent Maple Syrup Urine Disease
An otherwise normal teenager has been coming to your office over the last few months with complaints of a maple-syrup odor and anorexia, further testing also shows ketonuria
72
Thiamine Responsive Maple Syrup Urine Disease
10 year old comes to your office and the mother complains of a maple-syrup like odor, tells you that the child has not been eating well, is irritable and lethargic, you suspect an amino acid metabolism disorder with residual enzyme activity, so you treat with thiamine and notice improved leucine tolerance
73
Phenylketonuria
Patient presents with a Mousy odor, skin
conditions, decreased skin and hair pigmentation, Severe mental retardation,
microcephaly,epilepsy and behavioural problems, urine analysis shows high levels of phenylalanine ketones
74
Maternal Phenylketonuria
Infant presents with congenital heart disease, intrauterine and post natal growth retardation microcephaly and mental retardation in the child, you suspect that the mother has a disorder that caused these symptoms
75
Hartnup Disease
Patient presents with photosensitivity rash, ataxia and neuropsychological problems, (diarrhea, dermatitis, dementia) blood work shows increased tryptophan levels, you suspect it is a defect in tryptophan uptake
76
Cystinuria
Patient comes in complaining of flank pain, examination shows kidney stones, pathology report shows they contain sulfur
77
Ornithine TransCarbamoylase Deficiency
failure to thrive, comatose baby, blood picture shows normoglycemia, blood pH is alkaline, you suspect an X-linked dominant disorder and treat with nitrogen scavengers
78
Homocystinuria
Lack of cystathione synthase, patient presents with arachnodactyly, osteoporosis and ectopic lentis, also see developmental delay
79
Cystathioninuria
benign condition caused by deficiency in cystathionine lyase
80
Porphyrias/Acute intermittent
"Dracula"
"Mad king George"
One of the ONLY disorders that are Autosomal Dominant EXCEPT congenital=autosomal recessive
Enzyme def- urophyrinogen 1 synthase or A block anywhere before urophyrinogen
Symptoms- abdominal pain & neuropsychiatric symptoms & red teeth
Other symptoms associated- photosensitive (build up in skin/mucous membrane)--> & anemia
Avoid drugs that induce cytochrome P450 which will increase heme synthesis
Treatment--> IV Hemin inhibits Ala synthase from cytosol to mitochondria
81
Alkaptonuria
30 yr old patient presents with degenerative arthritis, characterized by discolouration of the sclera and ear cartilage, blood work show deficiency in Homogenetisate oxidase and an accumulation of tyrosine
82
Hyperbilirubinemia/Prehepatic
Hemolytic jaundice- excess production of bilirubin
Due to hemolysis & Liver is NOT damaged
Signs to look for- high concentrations of unconjugated bilirubin in blood
Not water soluble so won't see it in Urine (minor) or feces (major pathway - urobilin)
83
Hyperbilirubinemia/intrahepatic
Symptoms- impaired uptake, conjugation and secretion of bilirubin
Reflects a generalized liver dysfunction BOTH unconjugated (blood) & conjugated (feces,urine) bilirubin --> due to blockage through the intestines see more discolored urine.
Associated- with other abnormalities in biochemical markers of liver function (high levels of AST & ALT-major precursor to diagnosis)
Damage to liver--> HEP A/B/C viral, physical trauma-->loss of appetite/fever
84
Hyperbilirubinemia/post hepatic
Caused by- obstruction to bilary tree aka gallstones or tumors
Signs- bilirubin in plasma is conjugated & bile acids accumulate (ALP-alkaline phosphotase BIG increase)
Symptoms- pale colored stools (absence of urobilin) and dark urine (increased conj. bilirubin)
NO bilirubin is going through intestine
85
Neonatal jaundice
Due to immaturity of enzymes (UDP glucuronyl transferase) in bilirubin conjugation (urine/feces form) due to premature birth
Physiologic- resolves in 10 days and high levels can cross BBB and cause Kernicterus (mental retardation)
Bilirubin levels get to high- treatment: phototherapy(helps conjugate bilirubin)--> converts bilirubin to water soluble form=nontoxic form, phenobarbital(induces P450 microsomal-increase synthesis of Heme), blood transfusion.
86
Crigler-Najjar syndrome
Autosomal recessive
Deficiency- bilirubin UDP glucuronyl transferase (conjugated bilirubin)
People affected- Amish
Type 1- complete absence in bilirubin conjugation
Type 2- reduction in bilirubin conjugation
87
Properties Associated with Disorders of Purine Metab.
Result of abnormal catabolism (breakdown of molecules into smaller units/release of energy) of purines
Manifestations arise from the insolubility of Uris acid
Excess Uric acid-->hyperuricemia or gout
Precipitation of sodium irate crystals in synovial fluid-->severe inflammation and arthritis
88
Gout
2 processes
1. Overproduction of Uric acid
2. Under excretion of Uric acid
Results from metabolic abnormality-->hyperuricemia --> sodium urate crystals
Symptoms- attacks of gouty arthritis or chronic arthritis
Primary gout- most common, inborn error, enzyme is defective
Secondary gout- less common, associated with renal disease, increased nucleic acid turnover, associated with inborn errors in metabolism of nucleic acid
TREATMENT- NSAIDS/corticosteroids anti-inflammatory (high doses), colchicine, Uricosuric agents increase Uric acid at kidney (probenecid, allopurinol-->inhibitor of xanthine oxidase, sulfinpyrazone)
89
Lesch Nyhan syndrome
Total Deficiency of HRPT (hypoxia thine guanine phosphoribosyl transferase) salvage pathway in purines NOT working
X linked recessive
Symptoms- hyperuricemia (renal failure, gouty arthritis and tophi), neurological disability (dystonia, spasticity & hyperreflexia), behavioral problems (cognitive dysfunction, aggressive, and self mutilation)
"Orange sand" in diapers--> Uric acid cyrstalluria causes micro hemorrhages in urethra
90
Syndrome x or Metabolic syndrome
Diagnosed with 3 or more factors below-
```
Android fat
Insulin resistance
Hypertroglyceridemia
Low serum HDL and high LDL
hypertension and increased risk for coronary artery disease
```
91
PEM (protein energy malnutrition)
Is a board term for a range of clinical syndromes
Inadequate dietary intake of protein and calories to meet the body's needs
Commonly found in children of the 3rd world
Marasmus and Kwashiorkor can present separately or together
92
Marasmus
Caused by: severe reduction in caloric intake
Symptoms: 60% reduction In body weight, children suffer from growth retardation, and loss of muscle/subcutaneous fat-->MOST seen in extremities (emaciated), Head appears too large for body, anemia & associated multivitamin deficiencies seen
93
Parkinsonism
Degeneration of substansia niagra
Loss of pigmented dopamine secreting cells
L-dopa used to treat it because it is made into dopamine
MAO inhibitors are used to help decrease breakdown of catecholemines --> accumulate in presynaptic space = ++reuptake
94
Adenosine Deaminase def.
Severe combined immunodeficiency
Down production of DNA and production of T lymphocytes (cell mediated directly & humeral indirectly B-cell)--> mostly effects Thymus
Bone marrow transplant or gene therapy
95
Vit. A deficiency
Onset: undernutrition/def. in absorption of fats
Symptoms: Night blindness, dry eye, bitot spots (opaque plaques lateral eye)
Total blindness due rupture of cornea (keratomalacia cornea soft) irreversible damage.
Upper resp/urinary passages-->secondary pulmonary infect. & renal/urinary stones
Total immune def.
96
Vit. A toxicity
Acute hypervitaminosis-->headache, vomiting (similar symptoms to brain tumor)
Chronic toxicity-->weight loss, nausea, dryness of mucosa
Retinoids should be avoided in preg. due to congenital malformations.
97
Vit. D deficiency - Rickets
Present in growing children-
Infants show craniotabes (excess of osteoid-unminerlized bone matrix)- exhibit Frontal bossing/squared appearance to head.
Deformity of chest-rosary or bumps
Bowing of long bones
In adults- regular bone growth not mineralized correctly-->excess osteoid (osteomalacia) leads to weak bones.
98
Hypovitaminosis E
PRIMARILY due to fat malabsorption can be seen in patients with Cholestasis, cystic fibrorsis
Main symptoms seen in Small intestine
99
Vit. K deficiency
Fat malabsorption-->Bilary tract disease
After use of antibiotics which kills intestinal bacteria
neonatal period-->liver reserves are small
Bleeding diathesis- intracranial hemorrhage, bleeding occurs everywhere, Treated with Vit.K
In adults- hematomas, hematuria, bleeding from the gums
Toxicity- causes hemolytic anemia/jaundice
100
Hereditary Nonpolyposis Colon Cancer
Autosomal Dominant
Defect in Mismatch repair pathway
Early adulthood onset without appearance of adenomatous polyps, heterozygous males 90% risk, females 70% risk
Affected cells are unable to remove small loops of unpaired DNA
101
Xeroderma Pigmentosa
Autosomal Recessive
Defect in nucleotide excision repair pathway
See sensitivity to sunlight (UV) with multiple skin cancers, early death (risk of skin cancer increased 1000-2000 fold)
See high levels of pyrimidine dimers in DNA
102
Transition mutation
Purine substitutes for a purine or pyrimidine substitutes for a pyrimidine
103
Transversion mutation
A pyrimidine substitutes for a purine, or a purine substitutes for a pyrimidine
104
Silent mutation
Undetectable change in the 3rd nucleotide of a code, due to the degeneracy of the genetic code
105
Missense mutation
different amino acid is incorporated into the protein due to a changed codon (ex. sickle cell)
106
nonsense mutation
Mutation causes a stop codon to be formed, see premature termination of the peptide chain
107
In frame deletion/insertion
Nucleotides are inserted/deleted in multiples of three
108
Frame shift deletion/insertion
A change in the reading frame due to a deletion/insertion of nucleotides into the sequence, see more severe mutations
109
Diptheria
See addition of ADP-ribose to eEF-2, so the ribosome cannot move during translation
