Biochem: Diseases Flashcards
Amino Acid Metabolism
No cystathionine synthase
Myocardial infarction, lens dislocation, osteoperosis
Homocystinuria
Amino Acid Metabolism
No homogentisate oxidase
Arthritis, black onchronotic pigments in cartilage, urine
Tx low protein diet
Alkaptonuria
Amino Acid Metabolism
High levels of valine, leucine and isoleucine in blood
Neuro problems, METAB acidosis
Tx with diet restriction, some with thiamin
MSUD
Amino Acid Metabolism
THE MOST COMMON CLINICALLY ENCOUNTERED INBORN ERROR OF AMINO ACID METAB
PKU
Amino Acid Metabolism
Dihydrobiopterine reductase deficiency
Mousey odor, hypopigmentation
Tx with diet restriction, supplement with BH4
PKU
Heme Metabolism
Differentiate Acute Intermittent Porphyria from Porphyria Cutanea Tarda
No photo sensitivity in PCT
Urine turns dark on sunlight with AIP
AIP: Uroporphyrinogen I synthase
PCTL Uroporphyrinogen III decarboxylase
Heme Metabolism
IV drug to alleviate acute porphyria attacks
Hemin
Heme Metabolism
Rate controlling step in synthesis
Formation of ALA from glycine and Succinyl-CoA via the ALA synthase enzyme (requiring B6 as a co-factor)
Heme Metabolism
2 enzymes inhibited by Lead
Ala synthase and ferrochelataas (for iron incorporation)
Nucleotide Metabolism
No HGPRT
EXCESS uric acid, gout
Involuntary movt disorders
Lesch-Nyhan syndrome also with self mutilation
Nucleotide Metabolism
Which nucleic acids lead to gout?
Purines only (Adenine and Guanine)
Nucleotide Metabolism
Large buildups of dATP
Die before 2 years of age
Lack of T and B cells
ADA deficiency which also leads to SCID.
Electron Transport Chain What is inhibited by: Cyanide Carbon monoxide Na azide Hydrogen sulfide
Cytochrome oxidase
Complex 4
Electron Transport Chain
What is inhibited by:
Dimercaprol
Antimycin a
Complex III: ubiquinone ferricytochrome
Electron Transport Chain What is inhibited by: Carboxin Malonate TTFA
Complex II: Succinate dehydrogenase
Electron Transport Chain What is inhibited by: Barbiturate Amytal Piercedin Roten Piercidin A
Complex I: NADH Dehydrogenase
Electron Transport Chain
What is inhibited by:
MELAS
Complex 1 NADH dehydrogenase
Electron Transport Chain
What is inhibited by:
Leigh disease
Complex 4 cytochrome oxidase
Electron Transport Chain
What is inhibited by:
Leber’s disease
Complex 3 ubiquinol ferricytochrome oxidase
Glycogen Storage Diseases
Hypoglycemia and lactic acidosis
Glycogen trapped in liver
(-) glucose 6 phosphatase
I: Von gierke
Glycogen Storage Diseases
Glycogen in lysosomes
Cardiomegaly and heart failure
(-) a-1,4 glucosidase (acid maltase)
II: Pompe
Glycogen Storage Diseases
Benign form of Von Gierke
(-) a-1,6 glucosidase (debranching enzyme)
III: Cori’s
IV: Andersen’s is the SEVERE form of 1 with NO branching enzyme
Glycogen Storage Diseases
Muscle cramps
MYOGLOBINURIA WITHOUT LACTIC ACIDOSIS
(-) skeletal muscle glycogen phosphorylase / myophosphorylase
V: McArdle
Glycogen Storage Diseases
McArdle twin with hemolytic anemia
Type 7 Tarui
Carbohydrate Metabolism
What enzymes are missing in Classic Galactosemia and Fructose intolerance?
Classic Galactosemia: Gal 1 phosphate uridyltransferase
Fructose Intolerance: Aldolase B
Fatty Acid Oxidation
Hypoglycemia
SIDS
Tx IV glucose
Medium chain fatty acyl coa dehydrogenase
Fatty Acid Oxidation
Akee tree, hypoglycin
Hypoglycemia
Jamaican vomiting sickness
Fatty Acid Oxidation
Phytanic acid buildup
Block beta oxidation
NEURO sxs sec to improper myelinization
Refsum’s disease
Fatty Acid Oxidation
Cerebrohepatorenal syndrome
NO peroxisomes to degrade VLCFA
Zellweger’s syndrome
Fatty Acid Oxidation
DEFECTIVE peroxisomes unable to degrade VLCFA
Adrenal insufficiency
X linked adrenoleukodystrophy
Dyslipidemias
NO app B48 and B100
Intestinal malabsorption, steatorrhea
Acanthosis
Abetalipoproteinemia
Dyslipidemias
INCREASED VLDL
CAD, DM T2, Obesity
T4 familial hypertriglyceridemia
Dyslipidemias
INCREASED RISK FOR ATHEROSCLEROSIS AND CAD
NO apo E
Aka Remnant removal disease
T3 familial dysbetalipoprotenemia
Dyslipidemias
INCREASED RISK FOR ATHEROSCLEROSIS AND CAD
xanthomas
NO LDL receptors
T2 Familial hypercholesterolemia
Dyslipidemias
NO INCREASED RISK FOR ATHEROSCLEROSIS AND CAD
xanthomas pancreatitis
NO lipoprotein lipase
Type 1 familial lipoprotein lipase
Dyslipidemias
NO Apo a1 (lack of ABC1 cholesterol transporter gene) = Cholesterol accumulates within the cells
Pathognomonic orange tonsils
HIGH TG
Tangier’s/ fisheye disease
Sphingolipidoses
Hepatosplenomegaly with erosion of long bones
No B-glucosidase
Gaucher’s disease
Sphingolipidoses
Hepatosplenomegaly
Increased sphingomyelin
Niemann-Pick disease
Sphingolipidoses Increase GM2 ganglioside No hexaminidaae A Cherry red macula MR hypotonia
Tay Sach’s disease
Sphingolipidoses
Rash
Renal failure
No alpha galactosidase
Fabry’s disease
Only X-linked recessive others autosomal
Sphingolipidoses Skin rash Hoarseness Bone malformation NO ceramidase
Farber’s dz
GAGS Corneal clouding Cardiomyopathy MR w/ gargoylism Onset age: 1, Death by age: 14
Type 1 Hurler’s syndrome
GAGS
NO corneal clouding
Cardiomyopathy
MR
Type 2 HUNTER’s syndrome
The only one X linked recessive
Others are all autosomal recessive
GAGS
NO MR
Skeletal dysplasia with short stature
Death due to atlanto-axial instability
Type 4 Morquio’s syndrome
The ONLY ONE WITHOUT MR!
GAGS Spasticity then loss of motor fxn MR Hyperactivity Loss of heparan sulfatase
Type 3 Sanflippo syndrome
Genetics
What is the usual genetic problem in enzyme defects?
Structural protein defects?
Recessive (x linked or autosomal)
Dominant
Genetics
Name common dzs with x linked inheritance
Duchenne muscular dystrophy Hemophilia A and B Chronic granulomatous dz G6PD Deficiency Agammaglobulinemia Wiskott Aldrich DI Lesch-Nyhan Fragile X Color blindness
Collagen Which type is defective in osteogenesis imperfecta? Late wound repair Cornea Fascia Dentin Bone
1
Collagen
Which type is defective in alport syndrome?
Basement membrane
4
ETC
Complex 5 is inhibited by?
Oligomycin
Collagen Which type is defective in ehler danlos? Granulation tissue Fetal tissue Uterus Skin Blood vessels
3
Type 2: cartilage, vitreous body, nucleus pulposus
BLOOD
What characteristic morphology is present in patients with G6PD deficiency?
Bite cells and Heinz bodies
DNA Repair Mechanisms
Ineffective Nucleotide Excision Repair - bulky thymine dimers
cannot tolerate sunlight
at risk for malignant melanoma, SCCA, BCCA, and fibrosarcoma
Xeroderma pigmentosum
Tx: 5-FU, Imiquimod
DNA Repair Mechanisms
DNA repair defect + Bone marrow failure
Cafe-au-lait spots
Susceptible to free radical damage
Fanconi Anemia
DNA Repair Mechanisms
Nucleotide excision repair defect, no risk for skin malignancies
Birdlike facies and dwarfism
Accelerated aging of cells
Cockayne syndrome
DNA Repair Mechanisms
Unstable genome
Progressive neurologic dysfunction, ataxia, sinopulmonary infections, telangiectasia
Ataxia-Telangiectasia
DNA Repair Mechanisms Mismatch DNA repair defect Prone to microsatellite instability 80% chance for Colon cancer 30-50% chance for type 3 Endometrial Cancer
HNPCC (Lynch syndrome)
DNA Repair Mechanisms
Higher frequency of p53 mutations
Disposition toward serous adenocarcinomas
60-80% Breast cancer risk
Risk for prostate, ovarian, and pancreatic CA
Hereditary Breast Cancer (BRCA1 or BRCA2)
DNA Repair Mechanisms
Helicase defect = genomic instability
Growth delay, increased risk of various malignancies by 300 fold, telangiectatic erythema
Bloom Syndrome
DNA Repair Mechanisms
Helicase defect
Scleroderma like skin, muscle atrophy, wrinkling of face, cataracts, osteoporosis.
aka Progeria of the Adult
Werner Syndrome
Collagen Diseases
Vit. C deficiency
weakening of the capillaries
Scurvy
Collagen diseases Brittle bones Blue sclerae Hearing loss Dental imperfections
Osteogenesis Imperfecta
Amino Acid Metabolism
Deficiency in tyrosinase
Albinism
Bilirubinemias
Defect in bilirubin-UGT
Criggler-Najar Type 1
Nucleotide Synthesis
Megaloblastic anemia, failure to thrive, (-) hyperamonemia
Tx: Oral uridine administration
Orotic aciduria
Chronic granulomatous disease is due to deficiency in?
NADPH oxidase
Molecular oxygen NOT converted to superoxide in leukocytes
