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Flashcards in Biochemistry Deck (110):
1

Lesch-Nyhan Syndrome


Defective purine salvage due to absent HGPRT
No conversion of hypoxanthine to IMP or guanine to GMP. Results in excess uric acid and de novo purine synthesis

X-linked Recessive
Hyperuricemia
Gout
Pissed off self mutilation
Retardation
Twitching (dystonia)

Treatment: allopuirnol of febuxostate (2nd line)

2

Adenosine Deaminase Deficiency

Excess ATP and dATP imbalances nucleotide pool via feedback inhibition of ribonucleotide reductase thus preventing DNA synthesis and decreasing lymphocyte count

Autosomal Recessive
SCID (sever combined immunodeficiency)

3

Herediatray Orotic Aciduria

Enzyme which makes UMP is defective

X-linked Recessive
↑ blood glutamine
Orotic Aciduria
Growth retardation

Treatment: uridine

4

Xeroderma Pigmentosum

Defect in xeroderma pigmentosum, which prevents the repair of pyrimidine dimers because of ultraviolet light exposure. Usually produces thymine dimers.

Autosomal Recessive
Sun sensitivity
Skin lesions and skin cancers
Ocular melanomas

5

Hereditary Nonpolyposis Colorectal Cancer (HNPCC) otherwise known as Lynch Syndrome

Impaired DNA mismatch repair

Autosomal Dominant
High risk of colon cancer as well as other cancers including endometrial, ovarian and stomach cancer

6

α-amanitin found in Amanita Phalloides (death cap mushrooms)

Inhibits RNA polymerase II

Sever hepatotoxicity

7

Li-Fraumeni Syndrome

p53 gene is mutated. Requires a second hit for pathology to come about.

8

Retinoblastoma

Cancer of developing retina. It is a mutation of RB gene which keeps it phosphorylated. First “hit” inherited and second mutation must occur in retinoblast to cause tumor formation.

Autosomal Dominant
90% penetrance

9

I-Cell Disease (inclusion cell disease)

Inherited lysosomal storage disorder. Failure of golgi to phosphorylate mannose residues (↓ mannose-6-phosphate) leading proteins to be excreted extracellularly rather than deliverd to lysosomes.

Autosomal Recessive
Inclusion bodies in lysosomes
Coarse facial features
Clouded corneas
Restricted joint movement
Often fatal

10

Kartagener Syndrome (primary ciliary dyskinesia)

Immotile cilia due to a dynein arm defect.

Results in infertility due to immotile sperm and disfunctional fallopian tube cilia
Increased risk of ectopic pregnancy
Can cause bronchiectasis
Recurrent sinusitis

11

Osteogenesis Imperfecta Type 1

Decreased production of Type 1 collagen used in bones, skin and tendons. Glycosylation of pro-α-chain hydroxylysine and formation of procollagen via hydrogen and disulfide bonds is impaired. Triple helix not formed properly.

Autosomal Dominant
Bones predisposed to fracture especially during birthing
Hearing loss
Blue sclera (whites of the eyes)
Dental imperfections

12

Alport Syndrome

Underproduction of Type 4 collagen leading to defective basement membrane.

X-linked
End-stage kidney disease
Visibly bloody urine
Protein in urine

13

Goodpasture Syndrome

Autoantibodies of Type 4 collagen leading to defective basement membrane.

Coughing up blood
Dry cough
Shortness of breath
Bloody urine
Burning sensation when urinating

14

Ehlers-Danlos Syndrome

Problem with reinforcement of many staggered tropocollagen molecules through covalent lysine-hydroxylysine cross-linkage (using lysyl oxidase/Cu2+). Collagen fibers not formed.

Variable Severity (Autosomal Recessive and Dominant)
Hyper-extensible skin
Hyper-mobile joints
Berry aneurysms and organ rupture (Vascular type with defective type III collagen)

15

Menkes Disease

Impaired copper absorption leads to connective tissue disease due to ↓ activity of lysyl oxidase.

Kinky hair
Growth retardation
Hypotonia

16

α - 1 Antitrypsin (Emphysema)

The serpina 1 gene on chromosome 14 codes for α1AT which protects tissues especially the lungs from neutrophil elastase. α1AT is made in the liver and secreted in circulation. Under normal conditions neutrophils protect lungs by killing microbes. At times the protease elastase escapes from the neutrophils and is inactivated by α1AT. Accumulation of miss-folded αLAT leads to liver damage and the inability to stop the effects of elastase.

Co dominance
Cirrhosis without drinking
Smoking/Alcohol can cause a second hit (but only one is necessary)

17

Marfan Syndrome

Mutation in the protein fibrillin which forms a glycoprotein sheath around elastic fibers of connective tissue. Affects skeleton, heart and eyes.

Autosomal Dominant
Very tall and thin
Arachnidactyly (long slender fingers)
Pectus excavadum (sunken chest)
High arched palate
Lens dislocation
Aortic insufficiency --> floppy mitral valve
Sublaxation of lenses, typically upwards

18

Epidermolysis Bullosa Simplex

Mutations in the cytokeratin genes that causes a failure of intermediate filament binding to the basement membrane.

Blistering caused by incidental trauma.

19

Angelman Syndrome

Paternal imprinting and a deleted maternal active gene. 5% of cases are uniparental disomy (two paternally imprinted genes). Deletion is on chromosome 15.

Severe mental retardation
Happy puppet syndrome (inappropriate laughter)
Seizures
Ataxia

20

Prader-Willi Syndrome

Maternal imprinting and a deleted paternal active gene. 25% of cases are uniparental disomy (two maternally imprinted genes). Deletion is on chromosome 15.

Hyperphagia: excessive hunger
Obesity
Intellectual disability
Hypogonadism
Hypotonia

21

Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Mutation in PKD1 (chromosome 16/85%) or (chromosome 4/15%).

Autosomal Dominant
Always bilateral enlargement of kidneys

22

Familial Adenomatous Polyposis

Colon becomes covered in adenomatous polyps after puberty. Mutations of chromosome 5 (APC gene). Colon must be resected.

Autosomal Dominant
Colon cancer

23

Familial Hypercholesteroemia

Defective or absen LDL receptor

Autosomal Dominant
Elevated LDL
Severe atherosclerotic disease early in live
Tendon xanthomas (classically Achilles tendon)

24

Hereditary Hemorrhagic Telangiectasia

Disorder of blood vessels

Autosomal Dominant
Telangiectasia (widened skin blood vessels)
Recurrent epistaxis
Skin discolorations
GI bleeding
Hematuria
Arteriovenous malformations

25

Hereditary Spherocytosis

Spectrin or ankyrin defect which leads to irregularly shaped RBC's.

Autosomal Dominant
Hemolytic anemia
↑ MCHC
Treat with splenectomy

26

Huntington Disease

Trinucleotide repeat disorder. Gene on chromosome 4. Decreasing age of onset through generations with progressively worse symptoms.

Autosomal Dominant
Depression
Progressive dementia
Choreiform movements (jerky) due to ↓levels of GABA

27

Marfan Syndrome

Mutation in the protein fibrillin which forms a glycoprotein sheath around elastic fibers of connective tissue. Affects skeleton, heart and eyes.

Autosomal Dominant
Very tall and thin
Arachnidactyly (long slender fingers)
Pectus excavadum (sunken chest)
High arched palate
Lens dislocation
Aortic insufficiency --> floppy mitral valve
Sublaxation of lenses, typically upwards

28

Multiple Endocrine Neoplasias (MEN)

Ret gene mutation (present in 2A and 2B)

Autosomal Dominant
Tumors in endocrine glands especially pancreas, parthyroid, pituitary, thyroid, and adrenal medulla.

29

Neurofibromatosis Type 1

Mutations in the NF1 gene on chromosome 17. 100% penetrance with variable expression.

Autosomal Dominant (variable expression)
Cafe-au-lait spots
Cutaneous neurofibromas

30

Neurofibromatosis Type 2

Mutation on chromosome 22.

Autosomal Dominant
Bilateral acoustic schwannomas (nerve sheath tumors)
Juvenile cataracts, meningiomas and ependymomas (tissues of CNS)

31

Tuberous Sclerosis

Neurocutaneous disorder with multi-organ system involvement

Autosomal Dominant (variable expression, incomplete penetrance)
Hamartomas (benign tumors)

32

Von Hippel-Lindau Disease

Deletion of VHL gene (TMS) on chromosome 3.

Autosomal Dominant
Both benign an malignant tumors

33

Autosomal Recessive Diseases

Albinism
ARPKD
Cystic Fibrosis
Glycogen Storage Diseases
Hemochromatosis
Kartagener Syndrome
Mucopolysaccharidoses (except Hunter)
Phenylketonuria
Sickle Cell Anemia
Sphingolipidoses (except Fabry)
Thalassemias
Wilson Disease

34

Cystic Fibrosis

Defect in CFTR gene on chromosome 7. Common deletion of Phe508. Most common lethal genetic disease in whites. ATP/Cl- channel that secrets Cl- into the lungs and GI tract is defective.

Autosomal Recessive
Abnormally thick mucous
Cl- concentration > 60 mEq/L, present in sweat
Bronchitis
ADEK deficiencies
Nasal polyps
Pancreatic insufficiency

Treatment: N-acetylcystein to loosen mucus plugs by cleaving disulfide bonds + dornase alfa to clear leukocytic debris.

35

X-linked Recessive Disorders

Be Wise, Fool's GOLD Heeds Silly HOpe

Bruton agammaglobulinemia
Wiskott-Aldrich Syndrome
Fabry Disease
G6PD deficiency
Ocular albinism
Lesch-Nyhan Syndrome
Duchenne (and Becker) muscular dystrophy
Hunter Syndrome
Hemophilia A and B
Ornithing transcarbamylase deficiency

36

Duchenne Muscular Dystrophy

X-linked frameshift mutation leading to truncated dystrophin protein which yields accelerated muscle breakdown. Dystrophin helps anchor muscle fibers, primarily those in the skeleton, heart. It connects the cytoskeleton (actin) to the dystroglycan transmembrane proteins which anchor into the ECM.

X-linked Recessive
Child onset
Weakness in pelvic girdle muscles which moves to superior muscles
Gower maneuver-patients use upper extremity to help them stand up
Pseudohypertrophy of calf muscles (fatty muscle)
Cardiomyopathy

37

Becker Muscular Dystrophy

X-linked point mutation in dystophin.

X-linked Recessive
Adolescent or early adulthood onset

38

Myotonic Type I

Trinucleotide repeat expansion in DMPK gene which leads to abnormal myotonin protein kinase

Trinucleotide Repeate Expansion Disease (anticipation)
Myotonia
Frontal balding
Cataracts
Testicular atrophy
Arrhythmia

39

Trinucleotide Repeate Expansion Diseases

X-Girlfriend's First Aid Helped Ace MY Test
Fragile X Syndrome cGg
Friedreich Ataxia cAa
Huntington Disease cAg
Myotonic Dystrophy cTg

40

Down Syndrome

Most common viable chromosomal disorder. Most common genetic intellecutal disability. Non-disjunction or translocation. Trisomy 21. First-trimester ultrasound shows increased nuchal translucency.

Falt Facies
Mental Retardation
Epicanthal folds
Large protruding tongue
Brushfield spots
Single palmar crease
Gap between 1st and 2nd toes

41

Edwards Syndrome

Non-disjunction resulting in trisomy 18.

Rocker-bottom feet
Mental retardation
Heart disease
Small lower jaw
Clenched hands
Low set ears

42

Patau Syndrome

Non-disjunction resulting in trisomy 13.

Mental retardation
Microphthalmia
Cleft lip and palate
Rocker bottom feet

43

Cri-du-chat Syndrome

Chromosome 5 terminal deletion (5p-)

Kitten like cry
Mental Retardation
Microcephaly
Hypertelorism

44

Williams Syndrome

Congenital microdeletion pf long arm of chromosome 7 (including elastin gene).

Elfin facies
Intellectual disability
Extreme friendliness with strangers
Well-developed verbal skills
Cardiocardiovascular problems

45

22q11 Deletion Syndromes

Microdeletion of chromsom 22q11

Velocardiofacial:
Cleft palate
Abnormal facies
Cardiac defects

DiGeorge Syndrome:
Thymic aplasia
Parathyroid defects
Cardiac defects
Hypocalcemia

46

Vitamin A: Retinol

Green leafy vegetables/liver/yellow & orange vegetables

Vision
Normal growth and reproduction
Maintenance of epithelial tissues

Night blindness (dry eyes, keratomalcia)
Dry scaly skin
Squamous metaplasia of the trachea, bronchi and renal pelvis

Toxicity:
Cerebral edema
Skin changes
Teratogenic
Osteoporosis

47

Vitamin D: "ciferols"

Dairy Products

Calcium metabolism
Promotes calcium/phosphorus absorption in the liver

Inadequate bone mineralization
Rickets in kids/osteomalacia in adults

48

Vitamin E:

Antioxidant (protects against radicals)
Integrity of membranes

Hemolytic anemia
Muscular dystrophy
Neurologic abnormalities

49

Vitamin K:

Grean and yellow vegetables and dairy products. Bacterial flora

Activator of precursors (through glutamyl carboxylation) of clotting factors (serine proteases)

Defective blood coagulation

50

Vitamin C:

Antioxidant
Hydroxylation in collagen synthesis
Absorption of iron
B-hydroxylase co-factor in catelcholamine synthesis

Scurvy
Defective formation of mesenchymal tissue and osteoid matrix.
Defective wound healing (hemmorhagic)

51

B1 - Tyrosine Pyro Phosphate

Whole grains, green leafy vegetables, fish, meat and dairy

Carbohydrate and AA Metabolism:
Transketolase (HMS, NADPH Synthesis)
Pyruvate Dehydrogenase (Formation of Acetyl-CoA)
Alpha-keto Glutarate (TCA cycle)
Branched Keto Acid Dehydrogenase (Carbon Degradation of valine and isoleucine)


Dry Beri Beri: Peripheral Neuropathy
Wet Beri Beri: High-output cardiac failure

Wernick-Korskoff Syndrome:
-Hemorrhagic lesions of cortical gray matter
-Mamillary bodies (under dicaphelon or brain)
-Confusion/Ataxia/Confabulation

52

B2 – Riboflavin (FAD)

Whole grains, green leafy vegetables, fish, meat and dairy

Deposits electrons into the ETC through complex II (succinate dehydrogenase)

Glossitis (cheilosis on angles of mouth)
Corneal vasclarization
Seborrhea(yellow scales) on face, genital

53

B3 – Niacin (as well as tryptophan )

Whole grains, green leafy vegetables, fish, meat and dairy

Can be used to raise HDL levels and lower VLDL levels

Reduction of glutathione
Synthesis of FA

Pellagra (Dermatitis exposed areas, Dementia, Death and Diarrhea)

54

B5 – Pantothenic Acid

Whole grains, green leafy vegetables, fish, meat and dairy

Coenzyme A

Listlessness
Fatigue
Burning feet syndrome

55

B6 – Pyridoxial Phosphate

Whole grains, green leafy vegetables, fish, meat and dairy

Amino acid transamination
Synthesis of niacin from tryptophan
Porphyrin synthesis,
Catelcholamine synthesis
GABA synthesis

Convulsions (decreased GABA firing)
Anemia (heme synthesis compromised)
Homocystinuria

56

B7 - Biotin

Whole grains, green leafy vegetables, fish, meat and dairy

Egg whites highly bind biotin

Carboxylation of Pyruvate, Acetyl –CoA, and Porpionyl-CoA

Anorexia
Glossitis (tongue)
Alopecia
Scaly Dermatitis

57

B9 - Folate

Whole grains, green leafy vegetables, fish, meat and dairy and fruits

Transfer of 1 Carbon Unit from dUMP N5,10 Methylene FH4 (DNA synthesis)

Megoblastic anemia
PMN nucleus with > 5 lobes
Homocysteinemia with risk of cardiovascular disease
Deficiency develops in 3-4 months
Normal methylmalonic acid

Deficiency caused by: phenytoin, sulfonamides, methotrexate

58

B12 – Coalbin

Intestinal bacteria and animal sources

Transfer of methyl group to homocysteine and conversion of methylmalonyl-CoA to succinyl-CoA

Lack of parietal cells due to autoimmune disorder in the stomach lead to intrinsic factor deficiency or damage to terminal ileum (Crohn Disease or Dihyllobotrium latum (tapeworm)). B12 is used in odd chain FA degradation, the degradation of AA acids, and the synthesis of purines.

Megoblastic anemia
PMN nucleus with > 5 lobes
Homocysteinemia with risk of cardiovascular disease
Methylmelonic aciduria: goes to neurons and into myelin sheaths
Progressive peripheral neuropathy
Deficiency develops in years

59

Kwashiorkor

Deficiency in only proteins but with adequate caloric intake. Typically in children less than 1 year of age who are not breast fed and receive starch rich, low protein diet

Depigmented bands with pales streaking in the hair or skin
Malbsorption
Edema
Anemia
Liver is fatty

60

Marasmus

Deficiency in all nutrients especially proteins and calories. Coexists with vitamin deficiencies
Typically in children less than 1 year of age who are not breast fed and do not have an adequate intake of substitute nutrients.

Muscle wasting

61

Essential Frutosuria

Deficiency in Fructokinase. Fructose re-enters blood.

Benign
Fructose in urea and blood

62

Hereditary Fructose Intolerance

Deficiency in Aldolase B. Fructose 1-P accumulates in liver and kidney and causes problems.

Hypoglycemia : Glucose production is inhibited
Liver Damage, Hyperbilirubinemia
Hyperuricemia (kidney function: level of uric acid in the blood that is abnormally high)
Renal Proximal Tubule Defect (Fanconi)

63

Lactose intolerance

Deficiency in Lactase. Most commonly inherited disease in the world. It is present in 90% of Asians, 50% of Mexicans, 80% of Africans.

Location: Intestine
Diarrhea: lactose is osmotic so it takes more water as it leaves the body
Bloating/cramps: bacteria in gut take up sugar but have no oxygen so they ferment the sugar and create methane, hydrogen gas and hydrogen sulfide

64

Galactosemia

Deficiency in Galactokinase or Gal 1P uridyl transferase. The latter is much more severe due to the trapping of Galactose 1P in the liver and brain.
Location: Liver and Brain

Galactokinase Deficiency:
Cataracts in early life

Gal 1P uridyl transferase Deficiency:
Cataracts in early life
Mental Retardation
Liver Damage, Hyperbilirubinemia
Lethargy, Vomitting, diarrhea

65

Deficiency in Pyruvate Kinase

Deficiency in Pyruvate Kinase (second most common reason for hemolytic anemia after G6PD deficiency). Glycolysis is one of only two pathways still present in erythrocytes along with HMS. Glycolysis is the only energy source since there is no B-oxidation or amino acid metabolism. If glycolosis is blocked then the cell membrane is destroyed because there is no energy in the cell. HMS is needed to reduce reactive oxygen species that can also destroy the membrane.

Location: Erythrocytes
Increased 2,3 Biphosphoglycerate: this enhances oxygen unloading because of a rightward shift of the oxygen dissociation cure. Cooperativity is the relative ease of adding additional 02. There is no change in the cooperativity of HbF because there is not B-unit for 2,3 BPG to bind. This is why HBF take O2 and never gives it back
No Heinz Bodies

66

Von Gierke

Glucose 6 Phosphatase Deficiency

Autosomal Recessive
Hyperlipidemia, increase
Hypoglycemia
Enlarged Liver
Lactic Acidosis
Protruding Abdomen
Growth failure
Emaciated Extremities
Doll like facies

67

Pompe

Lysosomal alpha-1,4 glucosidase Deficiency

Autosomal Recessive
Glycogen in inclusion bodies
Cardiomegaly
Early Death (by two years)
Muscle weakness

68

Cori Disease

debranching Enzyme (Amylo 1,6-glucosidase) Deficiency

Autosomal Recessive
Liver Enlargement
Mild Hypoglycemia: liver cannot rely on glycogen stores so uses blood glucose extensively
Glycogen with short outer branches with single glucose (alpha 1,4 not cleaved)

69

Anderson Disease (amylo-pectinosis)

Branching Enzyme (Amylo 4,6- glucosidase) Deficiency

Autosomal Recessive
Infantile hypotonia
Cirrhosis
Death by 2 years
Glycogen with very few branches especially towards periphery

70

Mcardle

Muscle Glycogen Phosphorylase Deficiency
(or PKA, phosphorylase kinase)

Autosomal Recessive
Muscle Cramps
Weakness on exercise
No lactate after exercise: glycolysis rate is high in liver because it can take up glucose using the GLUT 2 but in muscles the rate of uptake peaks and after strenuous exercise the sole source of glucose comes from glycogen breakdown
Myoglobinuria

71

Hers

Hepatic Glycogen Phosphorylase Dificiency

Autosomal Recessive
Mild fasting hypoglycemia: liver cannot rely on glycogen stores so uses blood glucose extensively
Hepatomegaly
Cirrhosis

72

Wernick-Korsakoff Disease

Point mutation in transketolase which reduces its affinity for TTP. Can be treated by giving TTP nutritionally (genetic disease helped nutrionally)

Ataxia,
Confusion and Opthalmplasia: due to reduced brain function

73

Beri Beri:

Nutritional deficiency in TTP which affects all TLCFN enzymes. Usually affects alcoholics because they have no TTP in diet. Wernick-Korsakoff Syndrome should be accompanied by other symptoms.

Dry Beri Beri: Neurological symptoms, muscle wasting

Wet Beri Beri: High cardiac output failure, edema

74

Chronic Granulomatous Disease

Defect in NADPH oxidase which leads to the inability to produce superoxide’s and kill microbes
Location: Neutrophils

Increased NADPH levels
Immunodeficiency

75

Methemoglobin

Defect in Methemoglobin Reductase or NADH from glycolysis which stops the ability to reduce Methemglobin back to Hemoglobin (Fe3+ Fe2+ does not happen) limiting the O2 carrying capacity of blood. Treatment occurs through the administration of methylene blue which chemically converts Met Hb  HB.

Location: Erythrocytes
Blue People because of hypoxia

76

Glycogen 6 Phosphate Dehydrogenase Deficiency

Not necessarily genetic. Africans have episodes under high oxidative stresses such as infections, drugs and fava bean ingestion. Mediterranean peoples have chronic condition because the level of enzyme is low all the time.
Location: Erythrocytes

X-linked
Heinz Bodies: because hydrogen peroxide oxidizes SH of hemoglobin and allows for disulfide bridges between Hb molecules
Hemolytic Anemia because hydrogen peroxide introduces holes in membrane
Immunodeficiency: Inactivation of NADPH oxidase in neutrophils because no NADPH

77

Hartnup Disease

Transporter for large neutral essential amino acids (tryptophan --> which makes niacin), if a little comes in it is lost by the kidney because it has the same defective transporter and cant keep it in.

Location: Intestine, Kidney
Pellegra like symptoms (Dermatitis, Diarrhea, Dementia)

78

Cysteinuria Disease

Transporter for large basic amino acids (lysine, arganine) as well as cysteine. Cysteine is lost in the urine and the cysteine SH groups will crosslinking forming cystine which is insoluble in water and accumulates.

Location: Intestine, Kidney
Autosomal Recessive
Renal Stones
UTI’s

79

Carbamoyl Phophate Synthetase Deficiency OR N-Acetylglutamate Deficiency

No orotic aciduria
Autosomal Recessive (rare)
Increased NH4 (hyperammonemia)
Increased Blood Gluatamine
Decreased BUN
Cerebral Edema (NH4 goes to brain)
Lethargy, Convulsions, Coma Death

80

Orthinine Trans Carbomylase (OTC) Deficiency



MOST COMMON
Orotic aciduria (X-linked): Increased Carbamyl Phosphate and spills in the cytoplasm and enters the pyrimidine (CUT) synthesis pathway. The precursor to these is orotic acid and since they are being made then orotic acid leaks out.
Increased NH4 (hyperammonemia)
Increased Blood Gluatamine
Decreased BUN
Cerebral Edema

81

Phenylketonuria

Pheynylalanine Hydroxylase or tetrahydrobiopterin are missing. Phenylalanine accumulates and a transaminase pops a NH2 off making phenylketones. Diet should be low in phenylalanine and supplemented withTyrosine.

Autosomal Recessive
Mental Retardation
Musty Odor
Microcephaly (impairs brain function)

82

Albinism

Tyrosine cannot be used to make melanin due to tyrosinase deficiency

Light colored skin, hair and eyes

83

Alcaptonuria

Accumalation of homogentistic acid which goes to urine due to homogentistate oxidase deficiency.

Autosomal Recessive
Dark blue/black urine - If red, orange its polyphuria, if tea/brown then bilirubiniemia
Arthritis
Ochronosis: Darkening of cartilage
Brown Sclerae

84

Maple Syrup Urine Disease

Accumalation ketoacids due to deficiency of branched chain ketoacid dehydrogenase

Autosomal Recessive
Maple Syrup Smelling Urine
Mental retardation
Ketosis
Death
Abnormal Muscle Tone

85

Methylmalonic Aciduria

Can differentiate between folate or B12 deficiency. Both cause megoblastic anemia and increased homocysteine.
Caused by:
B12 Deficiency
Mutase Defect
Pernicious Anemia (Intrinsic Factor Deficiency)

Increased Methylmalonic Aciduria
Peripheral Nerupathy

86

Fabry Disease

α-glactosidase A enzyme deficiency.
Leads to accumulation of trihexoside

X-linked Recessive
Peripheral neuropathy of hands and feet
Cardiovascular /renal disease
Angiokeratomas, lesion of capillaries leading to small dark red to purple raised spots

87

Gaucher Disease

Glucocerebrosidase (B-glucosidase) deficiency
Leads to accumulation of glucocerebrosidase

Autosomal Recessive
Most common sphingolipidose
Hepatosplenomegaly
Easy bone fracturing
Pancytopenia
Crumpled tissue paper inclusions in macrophages

88

Tay-Sachs Disease

Hexosaminidase A deficiency
Leads to accumulation of GM2 ganglioside

Autosomal Recessive
Progressive neurodegeneration and developmental delay
No startle reflex
"Cherry red" spot on macula
No hepatosplenomegaly

89

Niemann-Pick Disease

Sphingomyelinase deficiency
Leads to accumulation of sphingomyelin

Autosomal Recessive
Progressive neurodegeneration and developmental delay
"Cherry red" spot on macula
Hepatosplenomegaly
Zebra body inclusions (foamy macrophages)

90

Krabbe Disease

Galactocerebrosidase deficiency
Leads to accumulation of galactocerebroside, psychosine

Autosomal Recessive
Peripheral neuropathy
Developmental delay
Optic atrophy
Globoid cells

91

Metachromatic Leukodystrophy

Arylsulfatase A deficiency
Leads to accumulation of cerebroside sulfate

Autosmal Recessive
Central and peripheral demyelination with ataxia and dementia

92

Hurler Syndrome

α-L-iduronidase deficiency
Leads to accumulation of heparan sulfate, dermatan sulfate

Autosomal Recessive
Developmental delay
Gargoylism
Airway obstruction
Corneal clouding
Hepatosplenomegaly

93

Hunters Syndrome

Iduronate sulfatase deficiency
Leads to accumulation of heparan sulfate, dermatan sulfate

X-linked Recessive
Mild Hurler + aggresive behavior
No corneal clouding

94

Acute Respiratory Distress Syndrome

Dipalmitoylphophatidylcholine serves as a major component of lung surfactant and is present in the fetus by week 30 of gestation. Needed for proper inhalation

95

Steatorrhea

Fatty stools (>6%) due to exclusion of bile or pancreatic lipase or malabsorption.

TG in stool if due to exclusion of bile or pancreatic lipase
FA in stool if problem with malabsorption (can arise from ADEK, Linoleic and Linoenic Def. ) or a caloric Def.

96

Abetalipoproteinemia

Genetic dysfunction of the ApoB-48 protein

Serum TG Low
Serum cholesterol Low

97

Hyperlipidemia Ib

Familial lipoprotein lipase deficiency (rare)
Or apoC II deficiency (rare)

Autosomal recessive
Elevated triglyceride
Elevated chylomicron/VLDL
Red-orange eruptive xanthomas
Fatty Liver
Acute pancreatitis
Abdominal pain after fatty meal

98

Hypercholestremia IIA

LDL receptor deficiency

Autosomal dominant
Elevated cholesterol
Elevated LDL
Xanthomas of achilles tendon
Corneal arcus (gray ring around eyes)
Xanthelasmas (palm)
High risk of atherosclerosis & coronary artery disease

99

Tangier Disease


Decrease of ABC1: Transporter of HDL

Orange tonsils
Premature heart disease

100

Familial LCAT - LCAT Def. Cholesterol LDL - Renal Failure
- Anemia
- Cornea opacities

LCAT deficiency

Renal failure
Anemia
Cornea opacities

101

Myopathic CAT/CPT Deficiency

Leads defective carnitine shuttle

Autosomal Recessive
Muscle cramps, weakness
Hypoketotic hypoglycemia
Myoglobinuria: muscle lyse
Elevated muscle TG

102

MCAD Deficiency

MCAD Deficiency: LCAD is for long chains. MCAD is an isoform of Fatty acyl-CoA Deyhydrogenase for medium chains (8-10 carbons) and SCAD for shorter chains.

Autosomal Recessive
C8, C10 acyl carnitines in the blood
Dicarboxilicacidemia (in urine): when B-oxidation not working w-oxidation kicks in in the peroxisomes. Trying to get some ATP.
Fasting hypoglycemia: gluconeogenesis needs energy and that energy comes from B-oxidation
No ketone bodies
Acyl glycine

103

Jamaican Vomiting Sickness

Toxin from unripe fruit of akee fruit tree which inhibits acyl-CoA dehydrogenase

Hypoglycemia (Dicarboxilacidemia)

104

Adrenal Leukodystrophy

Peroxisomal disorder:

X-linked
Decrease of transport of very long fatty acids to peroxisomes
Adrenals, Mylein destroyed because they incorporate lipids
Cognitive deficiency leading to seizures
Visual impairment
Addisons
Neurons system detoriation

105

Zweweger Syndrome

Peroxisome biogenesis disorder

Increase long chain FA (phytonic acid)
Mylein disorders
Liver enlarged, mental retardation
Weakened muscles in children

106

Acute Intermittent Porphyria

Acute Intermittent Porphyria: Porphobiliogen Deaminase

Autosomal Dominant, late onset
No photosensitivity

Port-wine urine in patient
Painful abdomen
Polyneuropathy
Psychological disturbances
Precipitated by drugs, alcohol, and starvations

Never give barbituates : If you give a barbiturate then you increase P450 enzymes which require heme to work.

107

Porphyria Cutanea Tardea

Porphyria Cutanea Tardea: Most common porphyria caused by a deficiency of Uropphyrinogen Decarboxylase.

Autosomal Dominant, Late Onset
Tea colored or deep brown urine
Photosensitivity *: blistering/shearing of skin in light. Uropophyrinogen III accumulates (or porphyrinogens) which react with light to form porphyrins that produce O2 radicals.

108

Arsenic Poisoning

Binds to E1 component of PDH

Confusion
Diarrhea
Chronic Night Blindness

109

Indirect Hyperbilirubinemia:
Criglar-Najjar
Gilberts Syndrome
Kernicturus

Criglar-Najjar Syndrome: Deficiency in UDP-Glucoronyl Transferase. Jaundice and increased Indirect Bilirubin

Gilberts Syndrome: UDP-Glucoronyl Transferase works fine but not optimally (2-3 mg/dl) due to a point mutation
Condition is benign.

Increased indirect hyperbiligrubinemia occurs during hemolysis due to breakdowns of RBC's.

Low levels of conjugation enzymes in newborns leads to Kernicturus, bilirubin accumulates in the brain due to jaundice. In newborns you have HbF which needs to be destroyed and need to be replaced with new RBC called HbA to respond to 2,3 BPG. UDP-Glucoronyl Transferase levels may not be ready at birth. Treatment is phototherapy using blue light. Bilirubin will be broken downs to make water soluble products.

110

Direct Hyperbilirubinemia


Bile Duct Obstruction (clay like feces). Stones or tumors. Bilirubin cannot be pumped out into the bile. Since direct bilibrubin is water soluble if the unconjugated form is sent to the urine and gives it a characteristic TEA color.
Dubin Johnson (black pigmentation of the liver)(Rotor Syndrome)