Step 1 Metabolic Disorders

Front 1

Adenosine deaminase deficiency

Back 1

Excess ATP and dATP imbalances the nucleotide pool via feedback inhibition of ribonucleotide reductase which prevents DNA syntehsis and thus decreases lymphocyte count.

Front 2

What does adenosine deaminase deficiency cause?

Back 2

It is one of the major causes of SCID=severe combined immunodeficiency disease.

Think bubble boy. SCID happens to kids and is the first disease to be treated by experimental human gene therapy.

Front 3

What are two purine salvage deficiencies?

Back 3

Adenosine deaminase deficiency

Lesch-Nyhan syndrome

Front 4

What are the findings in Lesch-Nyhan syndrome?

Back 4

retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis

Front 5

What is the issue in Lesch-Nyhan syndrome?

Back 5

defective purine salvage owing to absence of HGPRT which converts hypoxanthine to IMP and guanine to GMP.

This results in excess uric acid production.

He's Got Purine Recovery Trouble.

Front 6

What is the inheritance pattern of Lesch-Nyhan syndrome?

Back 6

X-linked recessive

Front 7

Ehlers-Danlos syndrome

Back 7

Faulty collagen synthesis causing
1) hyperextensible skin
2) tendency to bleed ( so easy bruising)
3) Hypermobile joints

Front 8

What can Ehlers-Danlos syndrome be associated with?

Back 8

joint dislocation, berry aneurysms, organ rupture.

Front 9

Ehlers-Danlos syndrome- what is most frequently involved?

Back 9

Type III collagen is most frequently affected.

Front 10

Osteogenesis imperfecta

Back 10

genetic bone disorder aka brittle bone disease caused by a variety of gene defects.

Most common form is autosomal dominant with abnormal type I collagen causing multiple fractures with minimal trauma, blue sclerae due to the translucency of the CT over the choroid, hearing loss, dental imperfections due to lack of dentin.

Type II is fatal in utero or neonate period

Front 11

Alport's syndrome

Back 11

Due to a variety of gene defects resulting in abnormal type IV collagen. Most common form is X-linked recessive. Characterized by progressive hereditary nephritis and deafness. May be associated with ocular disturbances.

Remember that Type IV collagen is an important structural component of the basement membrane of the kidney, ears, and eyes.

BM has basketweave appearance on EM.

Front 12

Marfan's syndrome

Back 12

caused by a defect in fibrillin. It affects skeleton, heart, and eyes.

Clinical findings: tall w/ long extremities, pectus excavatum, hyperextensive joints, and long,tapering fingers and toes, cystic medial necrosis of aorta, aortic incompetence and dissecting aortic aneurysms, flooppy mitral valve, subluxation of lenses.

Front 13

Emphysema cause (genetic cause)

Back 13

can be caused by alpha1-antitrypsin deficiency, resulting in excess elastase activity.

Front 14

Hypophosphatemic rickets

Back 14

formerly known as vitamin D-resistant rickets. Inherited disorder resulting in increased phosphate wasting at proximal tubule. Results in rickets-like presentation.

Front 15

Fragile X Syndrome

Back 15

X-lined defect affecting the methylation and expression of the FMR1 gene. Assocaited with chromosomal breakage. The 2nd most common cause of genetic mental retardation (after Down syndrome).

Findings: macro-orchidism, long face with a large jaw, large everted ears, autism, mitral valve prolapse.

Front 16

What are important X-linked recessive disorders?

Back 16

Be Wise, Fool's GOLD Heeds Silly Hope.
Bruton's agammaglobulinemia, Wiskott-Aldrich syndrome, Fabry's disease, G6PD deficiency, Ocular albinism, Lesch-Nyhan syndrome, Duchenne's (and becker's) mucular dystrophy, Hunter's Syndrome, Hemophilia A and B.

Female carriers are rarely affected due to random inactivation of an X chromosome in each cells.

Front 17

What are important autosomal recessive diseases?

Back 17

albinism, ARPKD, cystic fibrosis, glycogen storage diseases, hemochromatosis, mucopolysaccharidoses, phenylketonuria, sickle cell anemias, sphingolipidoses, thalassemias.

Front 18

What are the 4 trinucleotide repeat disorders?

Back 18

Huntington's disease (CAG)
MyoTonic (CTG)
FraGile X syndrome (CGG)
Friedreich's ataxia (GAA)

Front 19

Patau's syndrome

Back 19

trisomy 13
Findings: severe mental retardation, rocker bottom feet, microphthalmia, microcephaly, cleft lip / palate, holoprosencephaly, polydactyly, congenital heart disease,. Death usually occurs within 1 year of birth.

(think Puberty=13, Patau's trisomy 13)

Front 20

Edward's Syndrome

Back 20

Trisomy 18
Findings: severe mental retardation, rocker-bottom feet, micrognathia (small jaw), low-set ears, clenched hands, prominent occiput, congenital heart disease. Death usually occurs within 1 year of birth.
Most common trisomy resulting in live birth after Down syndrome.
Think E-lection age = 18 E-dward's syndrome =18

Front 21

Down Syndrome

Back 21

trisomy 21
Findings: mental retardation, flat facies, prominent epicanthal folds, simian crease, gap between 1st 2 toes, duodenal atresia, congenital heart disease (most commonly septum primum-type ASD). Associated with increased risk of ALL and Alzheimer's disease.

Front 22

Causes of Down Syndrome

Back 22

95% of cases due to meiotic nondisjunction of homologous chromosomes (associated with advanced maternal age; from 1:1500 in women <20 to 1:25 in women > 45)

4% of cases due to robertsonian translocation.

1% of cases due to Down mosaicism (no maternal association)

Front 23

Results of pregnancy quad screen when mom is pregnant with a fetus with Down Syndrome

Back 23

decreased AFP

increased beta-hCG

decreased estriol

increased inhibin A

Front 24

Cri-du-chat Syndrome

Back 24

Congenital microdeletion of short arm of chromosome 5 (46,XX or XY, 5p-)

Findings: microcephaly, moderate to severe mental retardation, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities

Cri-du chat = cry of the cat

Front 25

Williams syndrome

Back 25

Congenital microdeletion of long arm of chromosome 7 (deleted region includes elastin gene)

Findings: distinctive "elfin" facies, mental retardation, hypercalcemia (increased sensitivity to Vit D), well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems.

Front 26

22q11 deletion syndromes

Back 26

CATCH-22
Variable presentaiton, including cleft palate, abnormal facies, thymic aplasia (T cell deficiency), cardiac defects, hypocalcemia 2ndary to parathyroid aplasia, due to microdeletion at chromosome 22q11.

Due to aberrant development of 3rd and 4th branchial pouches.

Front 27

What are 2 examples of 22q11 deletion syndromes?

Back 27

DiGeorge syndrome: thymic, parathyroid, and cardiac defects

Velocardiofacial syndrome: palate, facial, and cardiac defects

Front 28

Marasmus

Back 28

energy malnutrition resulting in tissue and muscle wasting, loss of subcutaneous fat, and variable edema

Front 29

Kwashiorkor

Back 29

-protein malnutrition resulting in skin lesions, edema, liver malfunction (fatty change due to decreased apolipoprotein synthesis). Clinical pictures is small child with swollen belly.

Kwashiorkor results from a protein-deficient MEAL: Malnutrition, Edema, Anemia, Liver (fatty)

Front 30

Glycolytic enzyme deficiency

Back 30

Associated with hemolytic anemia. Inability to maintain activity of Na+-K+ ATPase leads to RBC swelling and lysis.

RBCs metabolize glucose anaerobically (no mitochondria) and thus depend solely on glycolysis.

Due to deficiencies in pyruvate kinase (95%), phosphoglucose isomerase (4%), and other glycolytic enzymes

Front 31

Pyruvate dehydrogenase deficiency

Back 31

Causes backup of substrate (pyruvate and alanine), resulting in lactic acidosis. Can be congenital or acquired (asin alcoholics due to B1 deficiency).

Findings: neurologic defects.

Tx: increased intake of ketogenic nutrients (high fat content or increased lysine and leucine which are the only purely ketogenic amino acids).

Front 32

Glucose-6-phosphate dehydrogenase deficiency

Back 32

X-linked recessive disorder, most common human enzyme deficiency. More prevalent amont blacks and increases malarial resistance. NADPH is necessary to keep glutathione reduced, which in turn detoxifies free radicals and peroxides. Decreased NADPH in RBCs leads to hemolytic anemia due to poor RBC defense against oxidizing agents.

Front 33

Fructose intolerance

Back 33

Hereditary deficiency of aldolase B. Autosomal recessive. Fructose-1-phosphate accumulates, causing a decrease in available phosphate, which results in inhibition of glycogenolysis and gluconeogenesis.

Sx: hypoglycemia, jaundice, cirrhosis, vomiting

Tx: decreased intake of both fructose and sucrose (glucose and fructose)

Front 34

Essential fructosuria

Back 34

Involes a defect in fructokinase. Autosomal recessive. A benign, asymptomatic condition, since fructose does not enter cells.

Sx: fructose appears in blood and urine.

Tx: milder symptoms than analogous disorders of galactose metabolism.

Front 35

Classic galactosemia

Back 35

Absence of galactose-1-phosphate uridyltransferase. Autosomal Recessive. Damage is caused by accumulation of toxic substances (including galactitol, which accumulates in the lens of the eye).

Sx: failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation.

Tx: excluse galactose and lactose (galactose + glucose) from diet

Front 36

Galactokinase deficiency

Back 36

Hereditary deficiency of galactokinase. Galactitol accumulates if galactose is present in diet. Relatively mild condition. Autosomal recessive.

Sx: galactose appears in blood and urine, infantile cataracts. May initially present as failure to track objects or to develop a social smile.

Front 37

What might be seen on a blood smear of someone with G6PD deficiency?

Back 37

Heinz bodies--oxidized hemoglobin precipitated within RBCs

Bite cells--result from the phagocytic removal of Heinz bodies of macrophages

Front 38

What are some things that can precipitate hemolysis in someone with G6PD deficiency?

Back 38

Oxidizing agents like fava beans, sulfonamides, primaquine, antituberculosis drugs.

Infection because free radicals are generated via inflammatory response can diffuse into RBCs and cause oxidative damage.

Front 39

Lactase deficiency

Back 39

age dependent and / or hereditary lactose intolerance (African Americans, Asians) due to loss of brush-border enzyme. May also follow gastroenteritis.

Sx: bloating, cramps, osmotic diarrhea

Tx: avoid dairy products or add lactase pills to the diet.

Front 40

Hyperammonemia

Back 40

can be acquired (from liver disease) or hereditary. Results in excess NH4+ which depletes alpha-ketoglutarate, leading to inhibition of TCA cycle.

Front 41

Symptoms of ammonia intoxication

Back 41

tremor, slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision

Front 42

Treatment of hyperammonemia

Back 42

limit protein in diet. Benzoate or phenylbutyrate (both of which bind AA and lead to excretion) may be given to decrease ammonia levels.

Front 43

Prader-Willi syndrome

Back 43

Due to deletion of normally active paternal allele on chromosome 15

Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia

Front 44

AngelMan's syndrome

Back 44

deletion of normally active maternal allele on chromosome 15.

mental retardation, seizures, ataxia, inappropriate laughter

aka "happy puppet"

Front 45

Onithine transcarbamoylase (OTC) deficiency

Back 45

most common urea cycle disorder. x-linked recessive. (other urea enzyme deficiencies are autosomal recessive).

This deficiency interferes with the body's ability to eliminate ammonia.

Often evident in the first few days of life, but may present with late onset. Excess carbamoyl phosphate is converted to orotic acid (part of the pyrimidine synthesis pathway).

Findings: orotic acid in blood and urine, decreased BUN, sx of hyperammonemia.

Front 46

What causes phenylketonuria?

Back 46

decrease in phenylalanine hydroxylase or decreased tetrahydrobiopterin cofactor. Tyrosine becomes essential. Increased phenylalanine leads to excess phenylketones in urine.

Front 47

Findings in phenylketonuria

Back 47

mental retardation, growth retardation, seizures, fair skin, eczema, musty body odor

It is autosomal recessive.

Front 48

Treatment for phenylketonuria

Back 48

decreased phenylalanine (contained in aspartame such as nutrasweet) and increase in tyrosine in diet

Front 49

Maternal PKU

Back 49

lack of proper dietary therapy during pregnancy.

Findings in infant: microcephaly, mental retardation, growth retardation, congenital heart defects.

Front 50

Alkaptonuria

Back 50

aka ochronosis

Congenital deficiency of homogentisic acid oxidase in the degradative pathway of tyrosine

autosomal recessive, benign disease.

Findings include dark CT, pigmented sclera, urine turns black on standing. May have debilitating arthralgias.

Front 51

albinism causes

Back 51

Congenital deficiency of either of the falling: tyrosinase- autosomal recessive OR defective tyrosine transporters (decreased amts of tyrosine and thus melanin).

Can result from a lack of migration of neural crest cells.

Front 52

inheritance and consequences in albinism

Back 52

Inheritance: variable due to locus heterogeneity vs ocular albinism which is X-linked recessive.

Consequences: lack of melanin results in an increased risk of skin cancer.

Front 53

Findings in homocystinuria

Back 53

Very much increase in homocysteine in urine, mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation (downward and inward), and atherosclerosis (stroke and MI).

Front 54

What are the 3 forms homocystinuria?

Back 54

ALL are autosomal recessive.

1) cystathionine synthase deficiency (tx: decreased Met and increased Cyst, and increased B12 and folate in diet)

2) decreased affinity of cystathionine synthase for pyridoxal phosphate (tx: increased vitamin B6 in diet)

3) homocysteine methyltransferase deficiency.

Front 55

What is common between the 3 forms of homocystinuria?

Back 55

All forms result in excess homocysteine and cysteine becomes an essential amino acid.

Front 56

What is cystinuria?

Back 56

Hereditary defect of renal tubular amino acid transporter for cysteine, ornithine, lysine, and arginine in the PCT of the kidneys.

Autosomal recessive. Fairly common (1:7000)

Front 57

What are the clinical effects of cystinuria and treatment?

Back 57

Excess cystine in the urine can lead to the precipitation of cystine kidney stones (cystine staghorn calculi).

Tx: acetazolamide to alkalinize the urine.

Front 58

Maple syrup urine disease

Back 58

blocked degradation of branched amino acids (Ile, Leu, Val) due to decrease in alphaketoacid dehydrogenase. Causes increase in alpha-ketoacids in the blood, especially Leu.

Causes severe CNS defects, mental retardation, and death. Urine smells like maple syrup.

Front 59

Hartnup Disease

Back 59

an autosomal-recessive disorder characterized by defective neutral amino acid transporter on renal and intestinal epithelial cells.

Causes tryptophan excretion in urine and absorption from the gut. LEADS TO PELLAGRA.

Front 60

Pellagra:

Back 60

The 3 D's: diarrhea, dermatitis, dementia.

can be caused by Vit B3 deficiency, Hartnup disease, malignant carcinoid syndrome, and INH (isoniazid).

Front 61

Von Gierke's disease

Back 61

type I glycogen storage disease

deficient in glucose-6-phosphatase

Findings: severe fasting hypoglycemia, very increased glycogen in the liver, increased blood lactate, hepatomegaly.

Front 62

Pompe's disease

Back 62

Type II glycogen storage disease

Deficient in lysosomal alpha-1,4-glucosidase (acid maltase)

Findings: cardiomegaly and systemic findings leading to early death.

Pompe's trashes the PUMP (heart, liver, muscle)

Front 63

Cori's disease

Back 63

Type III glycogen storage disease

Deficient in debranching enzyme (alpha-1,6-glucosidase)

Findings: milder form of type I with normal blood lactate levels.

Gluconeogenesis is intact.

Front 64

McArdle's disease

Back 64

type V glycogen storage disease

Deficient in skeletal muscle glycogen phosphorylase

Findings: increased glycogen in muscle, but can not break it down, leading to painful muscle cramps, myoglobulinuria with strenuous exercise.

McArdle's=Muscle

Front 65

What are the sphingolipidoses? (lysosomal storage diseases that result in the build up of sphingolipids)

Back 65

Fabry's disease, Gaucher's disease, Niemann-Pick disease, Tay-Sachs disease, Krabbe's disease, Metachromatic leukodystrophy

Front 66

What are the mucopolysaccharidoses? (lysosomal storage diseases that result in the build up of mucopolysaccharides)

Back 66

Hurler's syndrome

Hunter's syndrome

Front 67

Enzyme deficient in Fabry's disease

Back 67

alpha-galactosidase A

Front 68

Enzyme deficient in Gaucher's disease

Back 68

beta-glucocerebrosidase

Front 69

Enzyme deficient in Niemann-Pick Disease

Back 69

sphingomyelinase

Front 70

Enzyme deficient in Tay-Sachs Disease

Back 70

Hexosaminidase A

Front 71

Enzyme deficient in Krabbe's disease

Back 71

Galactocerebrosidase

Front 72

Enzyme deficient in Metachromatic leukodystrophy

Back 72

Arylsulfatase A

Front 73

Enzyme deficient in Hurler's syndrome

Back 73

alpha-L-iduronidase

Front 74

Enzyme deficient in Hunter's Syndrome

Back 74

Iduronate Sulfatase

Front 75

Inheritance and findings in Fabry's disease

Back 75

X-linked recessive

Findings: peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease

Front 76

Inheritance and findings in Gaucher's disease

Back 76

Autosomal recessive

Findings: hepatosplenomegaly, aseptic necrosis of femur, bone crises, Gaucher's cells (macrophages that look like crumpled tissue paper)

Front 77

Inheritance and findings in Niemann-Pick disease

Back 77

Autosomal Recessive

Findings: progressive neurodegeneration, hepatosplenomegaly, cherry-red spot on macula, foam cells

Front 78

Inheritance and findings in Tay-Sachs disease

Back 78

Autosomal recessive

Findings: progressive neurodegeneration, developmental delay, cherry-red spot on macula, lysosomes with onion skin, no hepatosplenomegaly (vs Niemann-Pick)

Front 79

Inheritance and findings in Krabbe's disease

Back 79

Autosomal Recessive

Findings: Peripheral neuropathy, developmental delay, optic atrophy, globoid cells

Front 80

Inheritance and findings in Metachromatic Leukodystrophy

Back 80

Autosomal recessive

Findings: central and peripheral demyelination with ataxia, dementia.

Front 81

Inheritance and findings in Hurler's Syndrome

Back 81

Autosomal Recessive

Findings: developmental delay, gargoylism, airway obstruciton, corneal clouding, hepatosplenomegaly

Front 82

Inheritance and findings in Hunter's Syndrome

Back 82

X-linked recessive

findings: mild Hurler's plus aggressive behavior, no corneal clouding

Front 83

Accumulated substrate in Fabry's disease

Back 83

ceramide trihexoside

Front 84

Accumulated substrate in Gaucher's disease

Back 84

glucocerebroside

Front 85

Accumulated substrate in Niemann-Pick disease

Back 85

sphingomyelin

Front 86

Accumulated substrate in Tay-Sachs disease

Back 86

GM2 ganglioside

Front 87

Accumulated substrate in Krabbe's disease

Back 87

Galactocerebroside

Front 88

Accumulated substrate in Metachromatic leukodystrophy

Back 88

cerebroside sulfate

Front 89

Accumulated substrate in Hurler's syndrome

Back 89

heparan sulfate, dermatan sulfate

Front 90

Accumulated substrate in Hunter's syndrome

Back 90

heparan sulfate, dermatan sulfate

Front 91

carnitine deficiency

Back 91

inability to transport LCFAs into the mitochondria resulting in toxic accumulation.

Causes weakness, hypotonia, and hypoketotic hypoglycemia

Front 92

acyl-CoA dehydrogenase deficiency

Back 92

Increased dicarboxylic acids, decreased glucose and ketones

Front 93

Type I dyslipidemia- what is it? what is increased?

Back 93

Hyperchylomicronemia

Chylomicrons are increased.

On blood test you will find elevated levels of triglycerides and cholesterol

Front 94

Type I dislipidemia pathophysiology

Back 94

Lipoprotein lipase deficiency OR altered apolipoprotein C-II.

Causes pancreatitis, hepatosplenomegaly and eruptive/ pruritic xanthomas (no increased risk for atherosclerosis).

Front 95

Type IIa dyslipidemia- what is it? what is increased?

Back 95

Familial hypercholesterolemia

LDL is increased

In the blood cholesterol will be increased

Front 96

Type IIa dyslipidemia pathophysiology

Back 96

Autosomal dominant absent or decreased LDL receptors.

Causes accelerated atherosclerosis, tendon (Achilles) xanthomas, and corneal arcus.

Front 97

Type IV dyslipidemia- what is it? what is increased?

Back 97

Hypertriglyceridemia

Increased VLDL

Will find elevated blood levels of triglycerides

Front 98

Type IV dyslipidemia pathophysiology

Back 98

hepatic overproduction of VLDL.

Causes pancreatitis.

Front 99

Abetalipoproteinemia

Back 99

Hereditary inability to synthesize lipoproteins due to deficiencies in apoB-100 and apoB-48.

Front 100

Inheritance of abetalipoproteinemia

Back 100

autosomal recessive

Front 101

Clinical findings in abetalipoproteinemia / onset

Back 101

Findings: failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness

Symptoms appear in the first few months of life.

Intestinal biopsy shows accumulation within enterocytes due to inability to export absorbed lipid as chylomicrons.

Front 102

Achondroplasia

Back 102

cell signaling defect of fibroblast grwoth factor receptor 3. results in dwarfism, short limbs, but head and trunk are normal size. associated with advanced paternal age.

Front 103

von Hippel-Lindau disease

Back 103

autosomal dominant

Findings: hemangioblastomas of retina / cerebellum / medulla; about half of affected individuals develop multiple bilateral renal cell carcinomas and other tumors.

associated with deletion of VHL gene (which is a tumor suppressor) on chromosome 3 (3p)

Results in constitutive expression of HIF (transcription factor) and activation of angiogenic growth factors. Von Hippel-Lindau=3 words for chromosome 3

Front 104

What are the autosomal dominant disorders?

Back 104

achondroplasia, ADPKD, FAP, Familial hypercholesterolemia (type IIA), Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome), Hereditary spherocytosis, Huntington's Disease, Marfan's syndrome, MENs, Neurofibromatosis type 1 (von recklinghausen's disease), Neurofibromatosis type 2, Tuberous sclerosis, von HIppel-Lindau disease

Front 105

Chediak-Higashi syndrome

Back 105

microtubule polymerization defect resulting in decreased phagocytosis.

Results in recurrent pyogenic infections, partial albinism, and peripheral neuropathy

Front 106

Kartagener's syndrome

Back 106

immotile cilia due to a dynein arm defect.

Results in male and female infertility (sperm immotile), bronchiectasis and recurrent sinusitis (bacteria and particles are not pushed out).

associated with situs inversus (organs are switched from left to right or right to left)

Front 107

Hereditary sideroblastic anemia. Defect and inheritance pattern

Back 107

X-linked

delta-aminolevulinic acid synthase gene is defective which interrupts heme synthesis.

Front 108

Lead Poisoning affected Enzyme

Back 108

Ferrochelatase and ALA dehydratase

Front 109

What is the accumulated substrate in lead poisoning?

Back 109

protoporphyrin (blood)

Front 110

Presenting symptoms in Lead Poisoning

Back 110

Microcytic anemia, GI, and kidney disease.

Children-exposure to lead paint and then mental deterioration.

Adults--environmental exposure (battery/ammunition/ radiator factory) with following symptoms of headache, memory loss, demyelination.

Front 111

Acute intermittent porphyria affected enzyme

Back 111

porphobilinogen deaminase (aka uroporphyrinogen-I-synthase)

Front 112

Acute intermittent porphyria accumulated substrate

Back 112

porphobilinogen, delta-ALA, uroporphyrin (urine)

Front 113

Acute intermittent porphyria presenting symptoms

Back 113

Symptoms= 5 Ps
Painful abdomen
Pink urine
Polyneuropathy
Psychological disturbances
Precipitated by drugs

Tx: glucose and heme, which inhibit ALA synthase.

Front 114

Porphyria cutanea tarda affected enzyme

Back 114

Uroporphyrinogen decarboxylase

Front 115

Porphyria cutanea tarda accumulated substrate

Back 115

uroporphyrin (tea-colored urine)

Front 116

Porphyria cutanea tarda presenting symptoms

Back 116

Blistering cutaneous photosensitivity. Most common porphyria.

Front 117

What enzyme deficiency causes Sideroblastic anemia (X-linked)?

Back 117

delta-aminolevulinic acid synthase -- rate limiting step

Glycine + succinyl-CoA converted delta-aminolevulinic acid

Front 118

What enzyme deficiency causes Lead poisoning?

Back 118

delta-aminolevulinic acid dehydratase

delta-aminolevulinic acid converted to porphobilinogen

Front 119

What 2 metabolic pathways is carbamoyl phosphate involved in?

Back 119

de novo pyrimidine synthesis and the urea cycle

Front 120

ornithine transcarbamoylase deficiency (urea cycle)

Back 120

leads to accumulation of carbamoyl phosphate which is then converted to orotic acid.

Will have increased orotic acid with hyperammonemia

Front 121

orotic aciduria- cause, findings, tx

Back 121

Cause: inability to convert orotic acid to UMP (de novo pyrimidine synthesis pahtwya) due to defect in either orotic acid phosphoribosyltransferase or orotidine 5'-phosphate decarboxylase. AUTOSOMAL RECESSIVE

Findings: increased orotic acid in urine, megaloblastic anemia (does not improve with admin of Vit B12 or folic acid), failure to thrive. No hyperammonemia... compare OTC deficiency

Front 122

I-cell disease

Back 122

inclusion cell disease--inherited lysosomal storage disorder.

Failure of addition of mannose-6-phosphate to lysosome proteins (enzymes are secreted outside the cell instead of being targeted to the lysosome).

Results in coarse facial features, clouded corneas, restricted joint movement and high plasma levels of lysosomal enzymes.

Often fatal in childhood.