Clinical Review

Front 1

HbS

Back 1

- βchain, Glu to Val on position 6
- anemia, pain, ↓ circulation
-

Front 2

HbC

Back 2

- β chain, Glu to Lysine
- mild anemia

Front 3

HbSC

Back 3

- sickle cell carrier + HbC
- undiagnosed until childbirth or surgery

Front 4

Methemoglobinemia

Back 4

- NADH cytochrome b5 reductaase
- ↓O2 carrying capacity of ferric Hb (
- headache, dyspnea, lightheadedness and chocolate cyanosis

Front 5

α Thalassemia silent carrier

Back 5

- 1 defective α chain
- no symptoms

Front 6

HbH

Back 6

- 3 defective α chains
- Accumulation of β4 tetramers in newborns, severe anemia

Front 7

HbB

Back 7

- 2 defective α chains
- Accumulation of γ4 tetramers in newborns

Front 8

Hydrops Fetalis

Back 8

- All 4 α-globin genes defective, fetal death

Front 9

β thalassemia major

Back 9

- both β chains are defective
- fatal

Front 10

β thalassemia minor

Back 10

- Only 1 β chain defective
- not fatal

Front 11

Scurvy

Back 11

- prolyl and lysyl hydroxylase
- vitamin C deficiency
- no hydroxylation of proline and lysine
- abnormal collagen,

Front 12

Ehlers-Danlos

Back 12

- lysyl hydroxylase
- Stretchy skin, loose joints, aortic aneurysm, ruptured colon,

Front 13

Osteogenesis Imperfecta

Back 13

- Brittle bones in babies, blue sclera, multiple fractures, slowed healing
- Type 1: heterozygous, postnatal, can survive
- Type 2: homozygous, perinatal, death in utero

Front 14

Emphysema

Back 14

- α1- anti-trypsin

Front 15

Alport’s

Back 15

- Affect glomerular basement membrane, hearing loss, occular defects, hematuria
- type IV collagen

Front 16

Goodpasture's

Back 16

- Antibodies destroy basement membrane of pulmonary and glomerular capillaries

Front 17

Menke's

Back 17

- Lysyl oxidase/Cu2+
- Deficient cross linking secondary to functional copper deficiency; depigmented
(steely) hair, arterial tortuosity and rupture, cerebral degeneration, anemia, osteoporosis.

Front 18

Complex I NADH dehydrogenase

Back 18

Amobarbital
Rotenone

Front 19

Complex III cytochrome reductase

Back 19

Antimycin A

Front 20

Complex IV cytochrome oxidase

Back 20

CO,CN

Front 21

complex V (ATP synthase)

Back 21

Oligomycin

Front 22

Fluoroacetate

Back 22

Inhibits TCA --> Aconitase

Front 23

Malonate

Back 23

Inhibits TCA --> Succinate dehydrogenase

Front 24

Arsenite

Back 24

Inhibits TCA --> α ketogluconate

Front 25

Leber's hereditary optic neuropathy

Back 25

- complex 1 (NADH dehydrogenase)
- degeneration of optic nerve

Front 26

Kearns-Sayre

Back 26

- mitochondrial dx
ragged red fibers
- heart block
- retinal pigmentation

Front 27

MELAS

Back 27

Mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like episodes

Front 28

MERRF

Back 28

Myoclonus epilepsy with ragged red fibers; ataxia, sensorineural deafness

Front 29

Pyruvate dehydrogenase deficiency

Back 29

- Pyruvate dehydrogenase
- Lactic acidosis, neurologic defects (Wernicke-Korsakoff)

Front 30

Pyruvate DH complex deficiency

Back 30

- Pyruvate DH complex
- Pyuvate to lactate, neonatal death, infancy death, episodic ataxia after meal

Front 31

Arsenic poisoning

Back 31

- G3PDH deficiency
- Lost NADH, pyruvate accumulates

Front 32

Pyruvate kinase deficiency

Back 32

- pyruvate kinase
- most common deficiency in glycolytic pathway
- hemolytic anemia and jaundice

Front 33

Classical galactosemia

Back 33

- GALT deficiency
- Cirrhosis, mental retardation, cataracts, galactosuria

Front 34

Galactokinase deficiency

Back 34

- galactokinase
- Cataracts, galactosemia, galactosuria

Front 35

UDP galactose 4-epimerase deficiency

Back 35

Benign: affects RBCs and WBCs Malignant: similar to GALT def

Front 36

Hereditary fructose intolerance

Back 36

- aldolase B deficiency
- toxic liver damage, renal disease, hypophophatemia, gout

Front 37

Essential fructosuria

Back 37

- fructokinase deficiency
- fructosuria

Front 38

Hemolytic Anemia

Back 38

- G6PD
- X linked, hemolytic anemia often induced by infections, oxidant drugs & fava beans;
- inadequate NADPH
production results in ↓ in antioxidant activity of glutathione in mature RBC’s
- Class I: chronic nonspherocytin anemia, most severe
- Class II: Mediterranean, normal stability, scarce activity in RBCs
- Class III: A-, oldest RBCs removed

Front 39

Amyotrophic Lateral Sclerosis

Back 39

- superoxide dismutase
- degenerated motor neurons in CNS

Front 40

Glycogen storage Disease Type 0

Back 40

- glycogen synthase
- hypoglycemia, death, hyperketonia

Front 41

Von Gierke's (Type 1)

Back 41

- Glucose 6-P
- hepatosplenomegaly
- severe fasting hypoglycemia

Front 42

Pompe (Type II)

Back 42

- α-1-4 glucosidase
(acid maltase)
- Infants: mental retardation, cardiomegaly, death by 2 yrs
- juvenile myopathy
- Adult: gradual skeletal myopathy

Front 43

Cori’s (Type III)

Back 43

- α-1-6 glucosidase
- Mild hypoglycemia, hepatomegaly

Front 44

Andersen’s (Type IV)

Back 44

- Glucosyl-4-6-transferase
- Hepatosplenomegaly, liver failure, death by 2 yrs

Front 45

McArdle’s (Type V)

Back 45

- Muscle glycogen phosphorylase
- Muscle cramping, fatigue, no increase in lactic acid after exercise

Front 46

Hers’ (Type VI)

Back 46

- Liver glycogen phosphorylase
- Mild hypoglycemia

Front 47

Hurler’s

Back 47

- α-L-iduronidase
- Corneal clouding, MR, coarse facial features, early death

Front 48

Hunter’s

Back 48

- Iduronate sulfatase
- X-linked, physical deformity, MR

Front 49

San Filippo's A

Back 49

- Heparin sulfate

Front 50

San Filippo's B

Back 50

- N-acetylglucosamidase

Front 51

San Filippo's C

Back 51

- N-acetyltransferase

Front 52

San Filippo's D

Back 52

- N-acetylglucosamine

Front 53

Scheie’s

Back 53

- α-L-iduronidase
- like Hurler's, but normal life span

Front 54

Sly’s

Back 54

- β-glucronidase
- Hepatosplenomegaly, physical deformity

Front 55

I-cell disease

Back 55

- Lysosomal hydrolytic enzymes
- Deficiency in ability to phosphorylate mannose residues of potential lysosomal enzymes
- results in incorrect targeting of glycoproteins
- death by 8 yrs
- elevated N-linked glycoproteins in urine

Front 56

Congenital α-β-lipoproteinemia

Back 56

- Apo B-48
- Accumulation of chylomicrons in enterocytes

Front 57

Type 1 hyperlipidemia (familial hyperchylomicronemia)

Back 57

- Apo C-II, Capillary lipoprotein lipase
- Accumulation of chylomicrons in plasma; high plasma TAGs and eruptive xanthomas (TAG deposits in skin)

Front 58

Type II hyperlipidemia

Back 58

- Genetic defect in synthesis, processing or functioning of LDL receptor
- elevated LDL levels
Familial hypercholesterolemia

Front 59

Type III hyperlipidemia (familial dysbetalipoproteinemia)

Back 59

- APO E
- Accumulation of chylomicron remnants in plasma

Front 60

Type IV hyperlipidemia

Back 60

↑ VLDL due to obesity, alcohol, diabeties

Front 61

Type V hyperlipidemia

Back 61

↑chylomicrons, TAGs, VLDL, pancreatitis

Front 62

Wolman Disease

Back 62

Cannot hydrolyze lysosomal cholesteryl esters

Front 63

Familial LCAT deficiency

Back 63

Complete absence of LCAT, low HDL

Front 64

Fish Eye Disease

Back 64

- partial absence of LCAT

Front 65

Zellweger syndrome

Back 65

- Defective peroxisomal biogenesis, accumulated VLCFAs in blood

Front 66

X-linked Leukodystrophy

Back 66

- Defective peroxisomal activation of VLCFAs, destroyed myelin

Front 67

Carnitine deficiency

Back 67

- inability to use long chain FA as fuel,
- causes: congenital, liver disease

Front 68

CAT-1 deficiency

Back 68

-Liver cannot synthesize glucose during fast, hypoglycemia, coma, death

Front 69

CAT-2 deficiency

Back 69

- Cardiomyopathy, muscle weakness following exercise

Front 70

Medium chain Fattyacyl CoA dehydrogenase deficiency

Back 70

- Decreased FA oxidation, severe hypoglycemia
- cause of 10% SIDS cases, Reyes syndrome; treat with
high carb diet

Front 71

Paroxysomal Nocturnal Hemoglobinuria

Back 71

- GPI synthase
- In hematopoietic cells

Front 72

Refsum disease

Back 72

- Fatty acid alpha-hydroxylase
- AR
- ↑ phytanic acid
- neurologic symptoms

Front 73

Vitamin B12 deficiency

Back 73

- Methylmalonic acidemia and aciduria, metabolic acidosis

Front 74

Niemann-Pick Type A

Back 74

- Sphingomyelinase
- Cherry red macula, hepatosplenomegaly, severe mental retardation, death in early childhood

Front 75

Niemann-Pick Type B

Back 75

- Chronic lung damage, death in early adulthood

Front 76

Neimann Pick Type C

Back 76

- Sphingomyelinase
- Cannot transport unesterified cholesterol out of lysosomes

Front 77

Tay-Sachs

Back 77

- β-hexoaminidase A
- Cherry-red macula ↑ GM2, blindness, MR, early death

Front 78

Gaucher's

Back 78

- β-glucosidase
- Sphingolipidosis, ↑glucocerebrosides, hepatosplenomegaly, MR, frequently fatal

Front 79

Metachromatic leukodystrophy

Back 79

- Arylsulfatase A
- MR, demyelination, fatal in 1st decade

Front 80

Krabbe’s

Back 80

- β-galactosidase
- ↑ galactocerebrosides, MR, almost total absence of myelin, fatal

Front 81

GM1 gangliosidosis

Back 81

- β-galactosidase
- GM1 accumulation, MR, skeletal deformities, death

Front 82

Sandhoff’s disease

Back 82

- β-hexosaminidase A & B
- ↑ globosides; same symptoms as Tay-Sachs with rapid progression.

Front 83

Fabry’s

Back 83

- α-galactosidase
- ↑ globosides; X linked, kidney & heart failure, redish purple skin rash

Front 84

Farber’s

Back 84

- ceraminidase
- ↑ ceramide, painful and progressively deformed joints; granulomas, fatal early in life

Front 85

3-β-hydroxysteroid dehydrogenase def.

Back 85

- ↑ pregnenolone; no glucocorticoids, mineralocorticoids, androgens or estrogens; early death

Front 86

17-α-hydroxylase deficiency

Back 86

- sex hormones and cortisol not produced
- ↑ production of aldosterone leads to hypertension
- phenotypically female but unable to mature

Front 87

21-α-hydroxylase deficiency

Back 87

- most common form of CAH (chronic adrenal hyperplasia)
- ACTH levels ↑ leading to ↑ sex hormones and masculinization

Front 88

11-β-hydroxylase deficiency

Back 88

- ↓ cortisol and aldosterone
- masculinization as with 21-α-hydroxylase deficiency

Front 89

Smith-Lemli-Opitz Syndrome

Back 89

- 7-hydrocholesterol-7-reductase
- AR, double bond migration (Lanosterol to Cholesterol)

Front 90

Classic PKU

Back 90

- phenylalanine hydroxylase
- mental retardation, fair skin (dec. melanin synthesis from tyrosine), mousy odour in affected individual, vomiting stimulating congenital pyloric stenosis
must screen for phenylalanine after child has been exposed to phenylalanine in breast milk
- Treatment: restrict phenylalanine, add tyrosine

Front 91

Malignant PKU

Back 91

- dihydrobiopterin reductase/dihydrobiopterin synthase
- similar symptoms as classic PKU; melatonin and serotonin synthesis also compromised
- Treatment: restrict phenylalanine, add tyrosine, L-dopa and 5-hydroxytryptophan

Front 92

Maternal PKU

Back 92

- mother has either Classic or Malignant PKU
- developmental abnormalities; microcephaly, mental retardation, occurs because mother didn’t observe dietary restrictions

Front 93

Alcaptonuria

Back 93

- homogentisate oxidase
- benign; homogentisate accumulates forming polymers that cause urine to darken upon standing; ochronosis; darkening of articular cartilage

Front 94

Maple Syrup Urine Disease

Back 94

- branched-chain ketoacid dehydrogenase
- levels of branched-chain α-amino acids and their α-keto analogues are elevated in plasma and urine
high mortality rate; neurologic problems

Front 95

Propionyl CoA Carboxylase Deficiency

Back 95

- Propionyl CoA Carboxylase
- Elevated propionate in blood; accumulation of odd chain FA in liver; developmental problems

Front 96

Cystathioninuria

Back 96

- Cystathionase
- Accumulation of cystathionine and metabolites, no clinical symptoms

Front 97

Homocystinuria

Back 97

- Cystathionine synthetase
- Accumulation of homocysteine in urine, elevated methionine & metabolites in blood, MR, osteoporosis

Front 98

Histidinemia

Back 98

- Histidase
- Elevated histadine in blood and urine, sometimes MR

Front 99

Albinism

Back 99

- Tyrosinase
- Inability to convert tyrosine to melanin

Front 100

Tyrosinosis

Back 100

- Eumarylacetoacetate hydrolase
- liver and kidney damage

Front 101

Nonketogenic hyperglycinemia

Back 101

- Glycine cleavage complex
- Severe mental deficiencies & low survival rate past infancy, inc. glycine in blood.

Front 102

Type I Hyperammonemia

Back 102

- Carbamoylphosphate synthetase I
- Within 24-48 hrs after birth infant becomes increasingly lethargic, needs stimulation to feed, vomiting,
hypothermia, & hyperventilation
- without appropriate intervention death occurs
- treat with arginine which
activates N-acetylglutamate synthetase

Front 103

N-acetylglutamate synthetase deficiency

Back 103

- N-acetylglutamate synthetase
- Severe/mild hyperammonemia associated wuth deep coma, acidosis, recurrent diarrhea, ataxia, hypoglycemia,
hyperornithinemia; treatment includes administration of carbamoyl glutamate which activates CPS I

Front 104

Type 2 hyperammonemia

Back 104

- Ornithine transcarbmoylase
- Most commonly occurring UCD, only X linked, increased ammonia and aa in serum, increased serum
orotic acid due to mitochondrial carbamoylphosphate entering cytosoland incorporating in pyrimidine
nucleotides leading to excess productin and excess catabolic products; treat with high carb, low protein diet,
and sodium phenylacetate/benzoate for ammonia detox

Front 105

Classic Citrullinemia

Back 105

- Argininosuccunate synthetase
- Episodic hyperammonemia, vomiting, lethargy, ataxia, seizures, coma; treat with arginine to increase
citruline excertion and sodium benzoate to detox ammonia

Front 106

Argininosuccinate Aciduria

Back 106

- Argininosuccinate lyase (argininosuccinase)
- Episodic symptoms similar to classic citrullinemia, elevated plasma and CSF argininosuccunate;
treat with argentine and sodium benzoate.

Front 107

Hyperargininemia

Back 107

- Arginase
- Rare UCD progressive spastic quadriplegia and MR high ammonia & arginine in CSF & serum, high arginine,
lysine, and ornithine in urine; treat with low protein diet including essential AA but no arginine

Front 108

Acute Intermittent porphyria

Back 108

- Uroporphyrinogen synthase
- Autosomal dominant, inc. porphobilinogen & ALA in urine, attacks precipitated by drugs that induce
cytochrome P450 in liver

Front 109

Congenital erythropoietic porphyria

Back 109

- Uroporphyeinogen III synthase
- ↑ uroporphyrinogen I & uroporphyninI

Front 110

Prophyria Cutanea Tarda

Back 110

- Uroporphyrinogen decarboxylase
- ↑ uroporphyrinogen III which converts to uroporphyrinogen I & coproporphyrinogen I

Front 111

Hereditary Coproporphyria

Back 111

- Coproporphyrinogen oxidase
- ↑ coproporphyrinogen III

Front 112

Varigate Porphyria

Back 112

- Protoporphyrin oxidase
- Accumulation of protoporphyrinogen IX

Front 113

Erythropoietic Protoporphyria

Back 113

- Ferrochelatase
- Accumulation of protoporphyrin IX

Front 114

Sideroblastic Anemia

Back 114

- ALA synthase
- X-linked

Front 115

Crigler-Najjar syndrome

Back 115

- Bilirubin glucuronyl transferase
- In newborns: newborn jaundice, treat with blue light

Front 116

Lead poisoning

Back 116

- Ferrochelatase/ ALA dehydratase
- ↑ ALA and protoporphyrin XI, DEC. heme