Biochemistry-Principles and Diseases Flashcards

Question

Angelman Syndrome- Description and findings

Answer 1

Paternal imprinting: Paternal gene is silent and Maternal gene is mutated/deleted. (5% of cases due to paternal uniparental disomy) Findings: Inappropriate laughter, seizures, ataxia and severe intellectual disability. "Happy Puppet" Think: "angelMan's = deletion of Maternal gene"

Answer 2

X-linked disorder due to frameshift mutation in the dystrophin gene. Impairs muscle regeneration. Findings: Weakness beginning in pelvic girdle and progressing superiorly. Psuedohypertophy of calf muscles due to fibrofatty replacement of muscle. Pts may show 'Gower maneuver.' Onset before 5 yrs of age. Death due to dilated cardiomyopathy common. Labs show elevated CPK and aldolase. Confirm with muscle biopsy.

Answer 3

Autosomal recessive defects in the CFTR gene on Ch 7. Common is deltaF508. Defects cause increased intracellular Cl- which in turn causes increased absorption of Na+ to counter. This causes H20 resorption and abnormally thick mucus plugs in the airways and GI tract. Increased Cl- in sweat test is diagnostic. (CFTR reabsorbs Cl- in sweat glands) Findings: Recurrent pulmonary infections, chronic bronchitis and bronchiectasis in upper airways(!), pancreatic insufficiency, malabsorption with steatorrhea, and nasal polyps. Infertility in males, subfertility in females, and fat-soluble vitamin insufficiency. Meconium ileus in newborns(!) Treatment: N-acetylcystein to loosen mucus plugs, DNAse to clear leukocytic debris.

Answer 4

X-linked disorder similar to DMD but less severe. Due to non-frameshift insertions into dystrophin gene, leaving it partially functional. Presents in adolescence or early adulthood.

Answer 5

Autosomal dominant disorder caused by CTG trinucleotide repeat expansion in the DMPK gene which leads to abnormal expression of myotonin protein kinase. Findings: Myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia. Think: "My Tonia, My Testicles, My Ticker, My Toupee"

Answer 6

X-linked defect affecting the methylation and expression of the FMR1 gene. The 2nd most common cause of mental retardation after Down syndrome. Trinucleotide repeat disorder. (CGG) Findings: post pubertal macroochidism, long face with a large jaw, large everted ears, autism, mitral valve prolaps. Think: "fragile X = eXtra large testes, jaw, ears"

Answer 7

Fragile X syndrome = (CGG) Friedriech ataxia = (GAA) Huntington Disease = (CAG) Myotonic Distrophy = (CTG) Think: X-Girlfriend's First Aid Helped Ace My Test

Answer 8

Trisomy 21 (1:700)Most common cause of intellectual disability. 95% of cases due to maternal nondisjunction. Associated with advanced maternal age (>45 = 1:25) Findings: Intellectual disability, flat facies, single palmer crease, duodenal atresia, Hirschprung disease, congenital heart defect (ASD), increased risk of ALL and AML. Increased risk of Alzheimer disease (21 codes for amyloid protein) 1st Trimester: PAPP-A is down, free beta-hCG is up. Increased nuchal translucency and hypoplastic nasal bone 2nd Trimester: alpha-fetoprotein is down, beta-hCG is up, estriol is down, inhibin A is up

Answer 9

``` Trisomy 18 (1:8000) Think: "E(dwards)lection age = 18" Second most common trisomy resulting in live birth. ``` Findings: Severe intellectual disability rocker-bottom feat, micrognathia, low set ears, clenched hands with overlapping fingers, prominent occiput, congential heart disease. Death usually occurs before 1 year. Tri-screen: PAPP-A and beta-hGC are both down Quad-screen: alpha-fetoprotein, beta-hGC, estriol and inhibin A are all down

Answer 10

Trisomy 13 (1:15,000) Think: "P(atau)uberty age = 13" Findings: Severe intellectual disability, rocker-bottom feet, microphthalmia, microcephaly, cleft liP/Pallet, holoProsencephaly, Polydactyly, congenital heart disease, cutis aplasia. Death within 1 year. Tri-screen: PAPP-A and beta-hGC are both down, increased nuchal translucency

Answer 11

Congenital microdeletion of short arm of Ch 5. (46XX or XY, 5p-) Findings: Microcephaly, moderate to severe intellectual disability, mewing cry, epicanthal folds, cardiac abnormalities (VSD)

Answer 12

Congential microdeletion of long arm of Ch7. Section includes the Elastin gene. Findings: Distinctive 'Elfin' faces, intellectual disability, hypercalcemia, (increased sensitivity to Vitamin D), well-developed verbal skills, extreme friendliness with strangers, cardiovascular problems.

Answer 13

Microdeletion at 22q11. Variable presentation. Findings: Cleft lip and palet, Abnormal facies, Thymic aplasia, Cardiac defects, Hypocalcemia secondary to parathyroid aplasia, (CATCH-22) DiGeorge Syndrome- thymic, parathyroid and cardiac defects Velocardiofacial Syndrome- palate, facial and cardiac defects

Answer 14

Retinol Antioxidant, constituent of visual pigment, necessary for cellular differentiation. ATRA used to treat PML. Deficiency: night blindness (nyctalopia), dry scaly skin (xerosis cutis), corneal degeneration (keratomalacia), bitot spots conjunctiva, immunosupression Excess: acute toxicity- nausea, vamiting, vertigo and blurred vision. chronic toxicity- alopecia, dry skin, hepatic toxicity and enlargement, arthralgias and pseudotumor cerebri. Is teratogentic.

Answer 15

Thiamine. An essential cofactor for several dehydrogenase enzymes as TPP. Pyruvate Dehydrogenase (glycolysis to TCA) alpha-ketoglutarate dehydrogenase (TCA) Transketolase (HMP shunt) Branched-chaine ketoacid dehydrogenase Think "ATP: alpha-ketoglutarate dehydrogenase, Transketolase, Pyruvate Dehydrogenase" Deficiency: Impaired glucose breakdown-->ATP depletion, worsened by glucose infusion. High met tissues affected first. Malnutrition and alcoholism. NEVER give an alcoholic a bag of glucose without giving a slug of thiamine. Wernicke-Korsakoff: confusion, ophthalmoplegia, ataxia, confabulation, personality change, permanent memory loss. Damage to medial dorsal nucleaus of the thalamus, mammillary bodies Dry Beriberi: Polyneuritis, symmetrical muscle wasting Wet Beriberi: high-output cardiac failure, edema

Answer 16

riboflavin component of flavins FAD and FMN, used as cofactors in REDOX reactions. (B2= 2 ATP) Deficiency: Cheilosis (inflammation of lips, scaling and fissures at the corners of the mouth), Corneal vascularization. "The 2 C's of B2"

Answer 17

niacin constituent of NAD, NADP. used in REDOX reactions. Derivative of Tyrptophan. Synthesis requires vitamins B2 and B6. Used to to treat dislipidemia, lowers levels of VLDL and raises levels of HDL. Deficiency: Glossitis. Severe deficiency leads to pellagra: Diarrhea, Dementia, Dermatitis (C3/C4 dermatome rash 'collar', hyperpigmentation of sun-exposed skin) Excess: Facial flushing, (can be avoided by taking aspirin) hyperglycemia, hyperuricemia

Answer 18

Pantothenic acid "B5 is the PENTO-thenic acid" Essential component of coenzyme A and fatty acid synthase. Deficiency: Dermatitis (starts as burning on soles of feet) enteritis, alopecia, adrenal insuficiency

Answer 19

Pyridoxine Converted to PLP, a cofactor for AST/ALT, glycogen phosphorylase. Synthesis of cystathionine, heme, niacin, histamine, and neurotransmitters including serotonin, epinephrine, norepinephrine, dopamine and GABA Deficiency: Convulsions, hyperirritability, peripheral neuropathy, sideroblasitic anemias due to impaired heme synthesis and iron excess. Isoniazid and oral contraceptives can induce deficiency

Answer 20

Biotin Cofactor for carboxylation enzymes. Deficiency is rare. Dermatitis, alopecia, enteritis. Caused by antibiotic use or excessive ingestion of raw egg whites. (Avidin in egg whites)

Answer 21

Folate Converted to THF, coenzyme for 1-carbon transfer/methylation reactions. Important for synthesis of nitrogenous bases in DNA and RNA. Absorbed in jejunum. Found in foliage. Deficiency: Most common deficiency in US. Macrocytic, megaloblastic anemia, hypersegmented PMNs, glossitis, NO NEUROLOGICAL SYMPTOMS. Increased homocysteine, normal methylmalonic acid. Seen alcoholism and pregnancy. Supplement early in pregnancy.

Answer 22

Cofactor for homocysteine methyltransferase and methylmalonyl-CoA mutase. Reserve pool (several years) stored in liver. Deficiency: Due to absence of terminal ileum, dietary insufficiency, lack of Intrinsic Factor. Signs of macrocytic, megaloblastic anemia, hypersegmented PMNs, parasthesias, and degradation of DCML, CST, SCT d/t abnormal myelin. Associated with increased serum levels of homocysteine and methylmalonic acid, compare to B9 deficiency. Can cause permanent damage if prolonged.

Answer 23

ascorbic acid Antioxidant. Necessary for iron absorption by reducing it to Fe2+ state. Necessary for hydroxylation of proline and lysine in collagen synthesis. Necessary for Dopamine beta-Hydroxylase, which converts dopamine to NE. Ancillary treatment for methemoglobinemia. Deficiency: Scurvy. swollen gums, bruising, petechia, hemarthrosis, anemia, poor wound healing, perifollicular and subperiostial hemorrhages, 'corkscrew hair.' Weakened immune responses. Excess: N/V, fever, diarrhea, fatigue, calcium, oxalate nephrolithiasis, can increase risk of iron toxicity in predisposed individuals (transfusion patients, heriditary hemochromatosis)

Answer 24

D2=ergocalciferol, from plants D3=cholecalciferol, from milk and sun-exposed skin 25-OH D3= storage form 1,25-(OH)2D3=calcitriol= active form Increases intestinal absorption of calcium and phosphate, increases bone mineralization. Oral vitamin D is absorbed in the jejunum. Deficiency: Rickets in children, osteomalacia in adults, hypocalcemic tetany. Breastfed infants should receive oral vitamin D. Deficiency is exacerbated by low sun exposure, pigmented skin, prematurity. Other causes of low D include, liver failure, renal failure, alcohol use Excess: Hypercalcemia, hypercalciuria, loss of appetite, stupor. Seen in granulomatous diseases due to Mac secretion of alpha-hydroxylases.

Answer 25

Tocopherol, tocotrienol Antioxidant (protects RBCs and membranes). CAN ENHANCE THE ANTICOAGULANT EFFECTS OF WARFARIN Deficiency: Hemolytic anemia, acanthyocytosis, muscle weakeness, posterior column and spinocerebellar tract demyelination. Neurologic presentation may appear similar to B12 deficiency, but without megoblastic anemia or increases serum methylmalonic acid levels. Excess: leads to coagulopathy d/t prevention of synthesis of clotting factors.

Answer 26

phytomenadione, phylloquinone, phytonadione Cofactor for the gamma-carboxylation of glutamic acid residues on various proteins required for blood clotting. Factors II, VII, IX, X and protein C & S. WARFARIN is Vit K antagonist Deficiency: Neonatal hemorrhage with increased PT and PTT but normal bleeding time. Can occur after prolonged use of antibiotics. Give newborns vit K shot.

Answer 27

Mineral essential for the activity of 100+ enzymes and zinc fingers. Deficiency: Delayed wound healing, hypogonadism, decreased adult hair, dysguesia, anosmia, acrodermatitis enteropathica. May predispose to alcoholic cirrhosis.

Answer 28

Protein malnutrition resulting in skin lesions, edema d/t decreased plasma oncotic pressure, liver malfunction (fatty change d/t decreased apoliprotein synthesis). Clinical presentation is small child with swollen belly. MEAL: Malnutrition, Edema, Anemia, Liver (fatty)

Answer 29

Total caloric malnutrition resulting in muscle wasting, loss of subcutaneous fat and variable edema. Marasmus = Muscle wasting

Answer 30

Causes a buildup of pyruvate that gets shunted into lactate (via LDH) and alanine (via ALT) Findings: Neurologic defects, lactic acidosis, increased serum alanine in infancy Treatment: increase intake of ketogenic nutrients (high fat content or increased lysine and leucine) Lysine and Leucine- the onLy pureLy ketogenic aa.

Answer 31

X-linked recessive disorder, most common human enzyme deficiency. More common in blacks. Decreased NADPH in RBCs leads to hemolytic anemia due to oxidative membrane damage. Can be caused by fava beans, sulfonamides, primaquine, anti-Tb drugs, and inflammation. Findings: Heinz bodies and Bite cells on blood smear.

Answer 32

Defect in fructokinase. Autosomal recessive. Benign, asymptomatic condition, since fructose is not trapped in cells. Findings: fructose appears in blood and urine

Answer 33

Autosomal recessive defect in Aldolase B. Fructose-1-P accumulates in cells, causing decrease in available P which stops glycogenolysis and gluconeogenesis. Findings: Urine (-) for fructose but (+) for reducing sugars. hypoglycemia, jaundice, cirrhosis, vomiting Tx: decrease intake of both fructose and sucrose

Answer 34

Autosomal recessive deficiency of galactokinase. Galactitol accumulates if galactose is present in diet. Findings: galactose appears in blood and urine, infantile cataracts, may present as failure to track objects or develop a social smile.

Answer 35

Autosomal recessive abscence of galactose-1-P Uridyltransferase. Accumulation of toxic substances. Findings: Failure to thrive, jaundice, hepatomegaly, infantile cataracts, intellectual disability. Can lead to E. coli sepsis in neonates.

Answer 36

An acquired or hereditary condition that results in excess NH4+, which depletes alpha-ketoglutarate, leading to inhibition of the TCA cycle. Findings: Tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision Tx: limit protein in diet, Lactulose to acidify the GI tract and trap NH4+ for excretion. Rifamixin to decrease colonization of ammoniagenic bacteria, Benzoate or phenylbutyratem, which bind amino acids can be given to decrease NH4+ levels.

Answer 37

Required cofactor for carbamoyl phosphate synthetase I. Absence of N-acetylglutamate leads to hyperammonemia Findings: Presents in neonates as poorly regulated respiration and body temperature, poor feeding, developmental delay, intellectual disability (identical to presentation of carbamoyl phosphate synthetase I deficiency)

Answer 38

Most common urea cycle disorder. X-linked recessive! (All other urea cycle enzyme deficiencies are Autosomal Recessive). Interferes with the bodies ability to eliminate ammonia, often presents in first few days of life but may present later. Excess carbamoyl phosphate is converted to orotic acid. Findings: Increased orotic acid in blood and urine, decreased BUN, symptoms of hyperammonemia, NO MEGALOBLASTIC ANEMIA (In contrast to orotic aciduria)

Answer 39

Autosomal recessive. Screening 2-3 days after birth because mother's enxzyme covers. Due to Phe-hydroxylase deficiency or deficiency in BH4. Tyrosine becomes essential, increase in levels of Phe, ketones in urine. Findings: intellectual disability, growth retardation, seizures, fair skin, eczema, musty body odor. Tx: diet, BH4 supplementation Complications: Maternal PKU- microcephaly, intellectual disability, growth retardation, congenital heart defects.

Answer 40

Autosomal recessive. Blocked degradation of BRANCHED amino acids. (Isoleucine, Leucine, Valine) due to decreased alpha-Ketoglutarate Dehydrogenase [(B1) Thiamine. Essential cofactor]. Leads to buildup of alpha-ketoacids in blood. Findings: Urine smells like maple syrup. Causes severe CNS defects, intellectual disability and death. Tx: Dietary restriction and B1 supplementation Think: " I(soleucine) L(eucine)ove V(aline)ermont MAPLE SYRUP from BRANChED maple trees."

Answer 41

Autosomal recessive, usually benign. Congenital deficiency of homogentisate oxidase in the degradative pathway of Tyr to fumarate. Pigment-forming homogentisic acid accumulates in the tissues. Findings: Dark connective tissue, brown pigmented sclera, urine turns black on prolonged exposure to air. May have debilitating arthralgias.

Answer 42

Glycogen storage disease (Type I). Autosomal recessive deficiency in G-6-Ptase. Findings: Severe fasting hypoglycemia, increased glycogen in the liver, increased blood lactate, increased triglycerides, increased uric acid and hepatomegaly. Tx: frequent oral glucose and cornstarch. avoidance of fructose or galactose.

Answer 43

Glycogen storage disease (Type II), autosomal recessive deficiency in Lysosomal alpha-1,4-glucosidase (acid maltase) Findings: Cardiolmegaly, hypertrophic cardiomyopathy, exercise intolerance and systemic findings lead to early death. Think: "Pompe trashes the Pump (heart)"

Answer 44

Glycogen storage disease (Type III). Autosomal recessive deficiency of glycogen de-branching enzyme (alpha-1,6-glucosidase). Milder form of Type 1 but gluconeogensis is intact.

Answer 45

Glycogen storage disease (Type IV). Autosomal recessive deficiency in skeletal muscle glycogen phosphorylase (myophosphorylase). Finding: Increased glycogen in muscle but muscle cannot break it down, leads to painful muscle cramps, myoglobinuria, with strenuous exercise and arrhythmias from electrolyte abnormalities. Blood glucose is usually not affected. Tx: Vit B6 (cofactor) Think: "McArdles= Muscle"

Answer 46

Von Geirkie (Type I)- Glu-6-ptase deficiency Pompe (Type II) - alpja-1,4-glucosidase Cori (Type III))- alpha-1,6-glucosidase McArdle (Type IV)- glycogen phosphorylase Think: "Very Poor Carbohydrate Metabolism"

Answer 47

Sphingolipidoses, lysosomal storage disease. X-linked recessive (!) deficiency in alpha-galactosidase A results in accumulation of ceramide trihexoside. Findings: Peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular/renal disease.

Answer 48

Most common lysosomal storage disease, sphingolipidoses. Autosomal recessive deficiency in beta-glucosidase ( Glucocerebrosidase), results in accumulation of glucocerebroside. Findings: Hepatosplenomegaly, pancytopenia, osteoporosis, aseptic necrosis of femer, bone crisis, Gaucher cells (lipid-laden osteoclasts). Tx: recombinant glucocerebrosidase

Answer 49

Lysosomal storage disease, sphingolipidoses. Autosomal recessive deficiency in sphingomyelinase, resulting in an accumulation of sphingomyelin. Findings: Progressive neurodegeneration, hepatosplenomegaly, foam cells and "cherry-red" (!) spot on macula. Think: No(neimann) man Pick's his nose with his sphinger."

Answer 50

Lysosomal storage disease, sphingolipidoses. Autosomal recessive deficiency in hexosaminidase A, resulting in the accumulation of GM2 ganglioside and fatty acid derivatives. Findings: Progressive neurodegeneration, developmental delay, "cherry red" spot on macula, no hepatosplenomegaly (!) as apposed to NPD. Think: " Tay-SaX lacks heXosamindase

Answer 51

Lysosomal storage disease, sphingolipidoses. Autosomal recessive deficiency in galactocerebrosidase leading to accumulation of glactocerebroside and psychosine. Findings: Peripheral neuropathy, developmental delay, optic atrophy, globoid cells. (looks like multinucleated giant cells)

Answer 52

Lysosomal storage disease, sphingolipidoses. Autosomal recessive deficiency in Arylsulfatase A, leading to accumulation of Cerebroside sulfate. Findings: Central and peripheral demyelination with ataxia and dementia.

Answer 53

Lysosomal storage disease, mucopolysaccharidosis. AR deficiency in alpha-l-iduronidase leading to accumulation of heparan sulfate and dermatan sulfate. Findings: Developmental delay, gargoylism, airway obstruction, corneal clouding, hepatosplenomegaly

Answer 54

Lysosomal storage disease, mucopolysaccharidosis. X-linked recessive (!) deficiency in iduronate sulfatase, leads to accumulation of heparan sulfate and dermatan sulfate. Findings: Mild-hurler + aggressive behavior, no corneal clouding (!) Think: "Hunter's see clearly and AGGRESSIVELY aim for the X(linked recessive)!"