Diseases in Biochemistry Flashcards by Bud Omar

Mitochondrial disease characterized by bilateral loss of central vision due to neuroretinal degeneration. This is characterized by deficiency in which complex of the ETC?

Leber’s Hereditary Optic Neuropathy Complex III

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Inherited condition due to NADH:Q oxidoreductase (Complex I) deficiency. It is caused by a mutation in mitochondrial DNA and may be involved in Alzheimer’s disease and DM.

MELAS (Mitochondrial encephalopathy, lactic acidodis and stroke)

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Prion diseases are characterized by alteration of the conformation and physical properties of proteins endogenous to the human host. Normal PrP is a glycoprotein rich in ___ (secondary structure) while PrPsc has many ____.

PrP: alpha helices
PrPsc: beta sheets

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Most fatal of the mitochondrial diseases characterized by deficiency in all complexes of the ETC

Fatal infantile mitochondrial myopathy

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Mitochondrial disease characterized by deficiency in Complex II

Kearns-Sayre Syndrome

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Mitochondrial disease characterized by deficiency in Complex IV

Leigh’s Disease

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Manifests as chronic hemolytic anemia, this condition is the most common enzyme defect in glycolysis.

Pyruvate kinase deficiency. Aldolase A is another glycolytic enzyme that may be deficient.

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The exercise capacity of patients with ___ is low particularly if they are on high carbohydrate diets. By providing lipid as an alternative fuel (during starvation), when blood free fatty acid and ketone bodies are increased, work capacity is impoved.

Muscle phosphofructokinase deficiency

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Most common biochemical cause of congenital lactic acidosis. What is the pattern of inheritance?

Pyruvate dehydrogenase deficiency. Because enzyme is deficient, pyruvate is shunted towards lactate production. Patients present with lactic acidosis and neurologic disturbance. X-linked dominant! There are only a few diseases that are X-linked dominant; another example is Alport Syndrome.

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Glycogen accumulation in liver and renal tubule cells; hypoglycemia; lactic acidemia; ketosis; hyperlipemia
Most likely diagnosis? Deficient enzyme?

Von Gierke’s Disease (Type I) Glucose-6-phosphatase

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Fasting hypoglycemia; hepatomegaly in infancy; accumulation of characteristic branched polysaccharide

Cori’s (or Forbe’s) Disease (Type III)
Debranching enzyme

MNEMONIC: ABCD
Andersen’s = Branching enzyme
Cori’s = Debranching enzyme

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Hepatosplenomegaly; accumulation of polysaccharide with few branch points. Death from heart or liver failure in first years of life

Andersen’s (Amylopectinosis) (Type IV)

Branching enzyme

MNEMONIC: ABCD
Andersen’s = Branching enzymeCori’s = Debranching enzyme

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Poor exercise tolerance. Muscle glycogen abnormally high. Blood lactate very low after exercise.

McArdle’s syndrome (Type V)
Muscle phosphorylase
McArdle’s = Muscle phosphorylase
HEr’s = HEpatic phosphorylase

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Hepatomegaly; accumulation of glycogen in liver; mild hypoglycemia; generally good prognosis

Her’s Disease (Type VI)Liver phosphorylase
McArdle’s = Muscle phosphorylase
HEr’s = HEpatic phosphorylase

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Poor exercise tolerance. Muscle glycogen abnormally high. Blood lactate very low after exercise. AND HEMOLYTIC ANEMIA

Tarui’s Disease

Muscle and erythrocyte phosphofructokinase I

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Hepatomegaly; accumulation of glycogen in liver; mild hypoglycemia; generally good prognosis

Her’s Disease (Type VI)

Liver phosphorylase

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In the rare hereditary condition, considerable quantities of L-xylulose appear in the urine because of the absence of the enzyme necessary to reduce L-xylulose to xylitol.

Essential pentosuria.

Aminopyrine and antipyrine increase the excretion of L-xylulose.

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Benign and asymptomatic condition whose only symptom is the appearance of fructose in blood and urine. What is the enzyme deficiency?

Essential fructosuria;

hepatic fructokinase

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Accumulation of glycogen in lysosomes.Juvenile form: muscle hypotonia, death from heart failure by2.Adult form: muscle dystrophy

Pompe’s Disease (Type II)
Lysosomal a1>4, a1>6 glucosidase (Acid maltase)
MNEMONIC: Pompe’s affects the pump (heart).

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Characterized by lack of hepatic fructokinase

Essential fructosuria

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Autosomal recessive condition in which galactitol accumulates causing cataracts within a few days of birth; vomiting and diarrhea after milk ingestion; hepatosplenomegaly; and mental retardation. This condition is due to deficiency in ___.

Classic galactosemia

Galatose-1-phosphate uridyltransferase

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Characterized by lack of aldolase B. Causes fructose-induced hypoglycemia because high levels of fructose-1-phosphate allosterically inhibit liver phosphorylase

Hereditary fructose intolerance

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A benign condition characterized by galactosemia, galactosuria and an increased tendency for cataracts

Galactokinase deficiency

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This condition is characterized by low levels of docosahexaenoic acid

Retinitis pigmentosa

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Inherited defect in fatty acid metabolism; affects only the liver; results in reduced fatty acid oxidation and ketogenesis, with hypoglycemia.

CPT-I deficiency

Inherited defect in fatty acid metabolism; affects mainly the skeletal muscle; results in reduced fatty acid oxidation and ketogenesis, with hypoglycemia.

CPT-II deficiency

Characterized by excretion of C6 - C10 dicarboxylic acids and by nonketotic hypoglycemia. What is the deficient enzyme?

Dicarboxylic aciduria | Medium chain acyl-CoA dehydrogenase

Hypoglycemia occurs after eating the unripe fruit of the akee tree, which contains hypoglycin - an inactivator of medium and short chain acyl-CoA dehydrogenase

Jamaican vomiting sickness

Neurologic disorder due to metabolic defect resulting in accumulation of phytanic acid found in dairy products and ruminant fat and meat.

Refsum's disease

Rare inherited absence of peroxisomes in all tissues. They accumulate C26 - C38 polyenoic acids in brain tissue; causing severe neurologic deficits.

Zellweger's syndrome

Most common leukodystrophy. This is characterized by deficiency in which enzyme.Symptoms include mental retardation, psychologic disturbances in adults. Demyelination.

Metachromatic leukodystrophy Arylsulfatase A MNEMONIC: This condition is characterized by psychologic disturbances. METAchromatic = ME TAMA sa ulo!

Name all glycogen storage disorders from Type I to Type VI

``` Viagra Pills Cause A Major Hard-on I: Von Gierke II: Pompe III: Cori IV: Andersen V: McArdle's VI: Her's ```

X-linked recessive disorder. Clinical symptoms include skin rash, kidney failure. Full symptoms are seen only in males.

``` Fabry's disease. MNEMONIC: FFAABBBRY Foam cells found in glomeruli and tubules Febrile episodes Alpha galactosidase A deficiency Angiokeratomas Burning pain in extremities BUN increased in serum Boys Renal failure YX genotype (male, X linked recessive) ``` Also ZeBRa bodies

Mutation in sickle cell anemia

"HbS isn't Very Good" At sixth position of Hb beta chain, Valine is present instead of Glutamic acid. SICKle cell = SIXth amino acid of Hb b chain

Triad of skin rash, hoarseness, bone malformation. WHat is the deficient enzyme?

Farber's Disease | Ceramidase

Characterized by hepatosplenomegaly, erosion of long bones, mental retardation in infants.

Gaucher's Disease | Deficiency in b-glucosidase

Deficiency in medium chain fatty-acyl dehydrogenase leads to fasting hypoglycemia. Pediatric patients are susceptible to this condition.

Sudden infant death syndrome

Characterized by mental retardation; myelin almost absent. Peripheral neuropathy, optic atrophy

Krabbe's disease Deficiency in b-galactosidase "The Crab Nebula is a GALaxy" Deficiency in galactocerebrosidase; Has GLOBOID cells

This disease is caused by a deficiency in: 1. b-glucosidase 2. b-galactosidase

1. Gaucher's 2. Krabbe's GaUchers: b-glUcosidase KrAbbe's: b-gAlactosidase

This condition is characterized by hepatosplenomegaly, mental retardation and is fatal in early life.

Niemann-Pick Sphingomyelinase MNEMONIC:Niemann Picks his nose with his sFINGERS (sphingomyelinase).

Which sphingolipidoses are characterized by the presence of a cherry-red macula?

Tay-Sach's Niemann-Pick's Parehong hyphenated

A deficiency in LDL receptor causes increased levels of LDL in the peripheral icrculation and an increased risk of atherosclerosis.

Familial hypercholesterolemia | Type II

Familial condition characterized by high VLDL and chylomicron, and low LDL and HDL. Patients are at increased risk for xanthomas and pancreatitis but with no increased risk for coronary atherosclerosis.

Familial lipoprotein lipase deficiency | Type I

Familial condition characterized by high levels of VLDL and chylomicron remnants. Patients are at an increased risk for coronary heart disease. Which is deficient in this condition?

Familial dysbetalipoproteinemia (Type III) Deficient ApoE

Familial condition characterized by increased VLDL production. Triad of CAD, DM type 2 and obesity

Familial hypertriglyceridemia | Type IV

Condition is characterized by intestinal malabsorption with accumulation of lipids in intestine and liver. No chylomicron and VLDL found in blood stream.

Abetalipoproteinemia | Deficient apo B

Characterized by deficiency in ABCA (ATP-binding casette transporter 1). Hallmark is hypertrophied orange tonsils

Tangier's disease | MNEMONIC: Tangier's = tangerine tonsils

Characterized by hepatosplenomegaly, erosion of long bones, mental retardation in infants.

Gaucher's Disease

In multiple sclerosis, there is loss both phospholipids and sphingolipids in the white matter. Which phospholipid in particular is lost in MS?

Ethanolamine plasmalogen

Characterized by deficiency in LCAT.Causes corneal opacification with hepatosplenomegaly.

Fish eye disease

In Alzheimer's Disease, this protein undergoes a conformational transformation from being rich in alpha helices to a state rich in beta sheets. The latter is prone to self-aggregation. Which apolipoprotein has been implicated as a potential mediator of this transformation?

B-amyloid | Apolipoprotein E

Patient presents with cyanosis, anxiety, headache and dyspnea. On extraction, blood was noted to be muddy brown in color. Diagnosis? Immediate treatment?

Methemoglobinemia (Fe3+ in heme which does not bind O2 but binds CN-) Mild: oral methylene blue or ascorbic acid Severe: IV methylene blue

Blood becomes "cherry pink" in color. Due to poisoning with an odorless gas; commonly seen in burn patients. Treatment?

Carbon monoxide poisoning CO has 200x greater affinity. Tx: Give 100% O2

An intrinsic defect in RBC membrane that renders erythrocytes less deformable and vulnerable to splenic sequestration. Defect in which protein? Diagnostic test?

Hereditary spherocytosis. Spectrin Osmotic fragility test

Condition characterized by high HDL levels, associated with benefits to health and longevity

Familial hyperalphalipoproteinemia

Condition characterized by decreased level or alteration in the structure of cardiolipin. Mitochondrial dysfunction causing heart failure and hypothyroidism

Barth syndrome

Condition characterized by hyperextensible skin, tendency to bleed, hypermobile joints and increased risk of berry aneurysm.

Ehlers-Danlos syndrome | Collagen III

Characterized by multiple fractures, blue sclerae, hearing loss and dental imperfections

Osteogenesis imperfecta | Collagen I

Presents with glomerulonephritis (hematuria), end-stage renal disease, and hearing deficits

Alport's syndrome | Collagen IV

In this condition, skin easily breaks and blisters as a result of minor trauma. Conditon is due to mutations affecting ___.

Epidermolysis bullosa (Collagen VII) Collagen VII forms delicate fibrils that anchor basal lamina to collagen fibrils in the dermis.

Patient all and thin, with dolichostenomelia, arachnodactyly, ascending aortic dilatation and dissection.

Marfan Syndrome | Fibrillin

Genetic cause of emphysema

A1-antitrypsin deficiency | Inhibits elastase

Patients homozygous for the trait present with mild hemolytic anemia. Hemoglobin variant has lysine at the 6th position instead of glutamate.

Hemoglobin C disease

Condition presents with lethargy, vomiting, hyperventilation, convulsions, cerebral edema, coma and death. May be treated with low protein diet

Hereditary hyperammonemia Type I: carbamoyl phosphate synthetase I Type II: ornithine transcarbamoylase In Type II, mothers also exhibit hyperammonemia and an aversion to high CHON diet.

Patient presents with hyperornithinemia, hyperammonemia, and homocitrullinuria. What is the underlying genetic defect?

HHH Syndrome Due to defect in ornithine transporter (transports ornithine from cytosol to mitochondria) Homocitrullinuria develops because transcarbamoylase (in the absence of ornithine), works with lysine to form homocitrulline.

Friable, tufted hair (trichorrhexis nodosa) associated with elevated levels of arginosuccinate in CSF, blood and urine. What is the deficient enzyme? Diagnostic test?

Arginosuccinase deficiency. Measurement of erythrocyte arginosuccinase activity on umbilical cord blood

Anemia, accumulation of Hb Barts. Patients present only after 8 months of life.

Beta thalassemia

Impairment in human selenoprotein have been implicated in tumorigenesis and atherosclerosis; and are associated with this selenium deficiency cardiomyopathy

Keshan Disease

1 - 2 g of citrulline daily is excreted in this disorder of urea metabolism.

Arginosuccinate synthetase deficiency

Condition characterized by urolithiasis, nephrocalcinosis and early mortality from renal failure or hypertension. If this was due to a defect in amino acid catabolism, what is the condition and which amino acid is involved?

Primary hyperoxaluria Defect is failure to catabolize glyoxylate which is oxidized to oxalate (increases stone formation). Glyoxylate is a product of deamination of GLYCINE.

Increased tendency to form stones due to defective reabsorption of a group of amino acids. What is the treatment?

Cystinuria No transporter for COAL Cystine, Ornithine, Arginine, Lysine Treat with acetazolamide to alkalinize the urine!

Deficiency in tyrosine aminotransferase leads to tyrosinemia

Richner-Hanhart Syndrome | Type II tyrosinemia

In this condition, the urine darkens on exposure to air. Later in the natural history of the disease, there is arthritis and connective tissue pigmentation. What is the condition? Enzyme defect? Pathophysiology of symptoms?

Alkaptonuria due to deficiency in homogentisate oxidase. Homogentisate is a product of tyrosine catabolism. Oxidation of homogentisate in the urine leads to darkening. Oxidation of homogentisate to benzoquinone acetate poiymerizes and binds to connective tissue, leading to arthritis and pigmentation (ochronosis).

Pellagra like signs and symptoms are seen due to impaired intestinal and renal transport of an amino acid.

Hartnup Disease Due to impaired transport of Tryptophan and neutral amino acids. Remember that Tryptophan is required for niacin synthesis

Condition characterized by mental retardation, growth retardation, fair skin, eczema and musty body odor

Phenylketonuria Due to deficiency in Phenylalanine Hydroxylase PHenylketonuria = Phenylalanine Hydroxylase

Lack of melanin increases the risk of skin Ca. This condition can result from a lack of migration of neural crest cells.

Albinism | Deficiency in Tyrosinase

This condition can cause mental retardation, osteoporosis, tall stature, kyphosis, lens subluxation, and atherosclerosis.

Homocystinuria due to: 1. Cystathionine synthase deficiency (with B6, converts homocysteine to cystathionine and then cysteine). 2. Low affinity for cystathionine synthase 3. Homocysteine methyltransferase deficiency (Converts homocysteine to methionine)

An autosomal recessive condition characterized by hyperargininemia. This condition does not present until patient has reached age 2 to 4 years.

Arginase deficiency

Photosensitivity or chronic inflammation to overt blistering and shearing in sun-exposed areas; abdominal pain and neuropsychiatric symptoms.The most common form is due to which enzyme deficiency.

Porphyria cutanea tarda | Deficiency in uroporphyrinogen decarboxylase

Due to a deficiency in alpha-ketoacid decarboxylase. Causes severe CNS defects, mental retardation and death. Causes increased alpha keto acids in the blood, esp leucine

Maple syrup urine disease

Most porphyrias are autosomal dominant except ____ which is characterized by deficiency in ___. Does NOT exhibit photosensitivity.

Congenital erythropoietic purpura (Autosomal recessive) Uroporphyrinogen III synthase

Porphyria which presents as decreased red cell counts and hemoglobin

X-linked sideroblastic anemiaALA synthase deficiency

Presents with abdominal pain and neuropsychiatric symptoms. Urinary delta-aminolevulinic acid is elevated.

ALA dehydratase deficiency

Rare autosomal recessive disorder characterized by severe congenital jaundice. Mutations in the gene encoding bilirubin-UGT is characteristic. Disease is often fatal within the first 15 months.

Type I Criggler-Najjar Type 2 is less severe; and can respond to large doses of Pb

Presents with headache, memory loss, peripheral neuropathy, nausea, abdominal pain, diarrhea. CBC demonstrates coarse, basophilic stippling of RBC

Lead poisoning

Benign autosomal recessive disorder consisting of conjugated hyperbilirubinemia. Centrilobular hepatocytes contain an abnormal black pigment derived from epinephrine.

Dubin-Johnson Syndrome | Mutation in MRP-2

Most common cause of unconjugated hyperbilirubinemia

Neonatal (physiologic) jaundice

Severe burning and aching of the feet, hyperesthesia, and vasomotor changes of the feet that leads to excessive sweating

Burning feet syndrome aka | Grierson-Gopalan syndrome

Megaloblastic anemia with degeneration of the spinal cord

``` Pernicious anemia (Vitamin B12 deficiency) ```

Unconjugated hyperbilirubinemia more common in males and entirely harmless

Gilbert Syndrome

Rare benign conjugated hyperbilirubinemia. Liver histology is normal. Precise cause unknown

Rotor Syndrome

Clinical manifestations include headache, nauseam ataxia related to increased CSF; hepatomegaly; thickening of long bones and hypercalcemia; and excessive dryness and desquamation of the skin.

Vitamin A toxicity

Photosensitive dermatitis, dementia, diarrhea

Pellagra (B3/niacin deficiency)

Triad of hyperuricemia, mental retardation and self-mutilation. Which two metabolites accumulate in this condition?

Lesch-Nyhan Syndrome HGPRT deficiency Lesch Nyhan = He's Got Purine Recovery Trouble PRPP and uric acid

Most important preventable cause of blindness

Vitamin A deficiency

Immunodeficiency in which both T cell and B cells are sparse and dysfunctional.

Adenosine deaminase deficiency ADA converts adenosine to inosine. With deficiency, adenosine builds up, converted to AMP and dATP which inhibits ribonucleotide reductase.

Cheilosis, desquamation, inflammation of the tongue and a seborrheic dermatitis

Riboflavin deficiency

Abnormal growth, megaloblastic anemia and excretion of large amounts of orotate in urine

Orotic aciduria Due to low activities: A. Orotidine phosphate decarboxylase B. Orotate phosphoribosyltransferase

Match condition with characteristic defect in DNA repair. 1. Xeroderma pigmentosum 2. Hereditary nonpolyposis Ca A. Mismatch repair B. Base excision repair C. Nucleotide excision repair D. Double-strand break repair

1. C | 2. A

Marked sensititivity to sunlight and subsequent formation of multiple skin Ca and premature death

Xeroderma pigmentosum Autosomal recessive Defect in nucleotide excision repair

Autosomal recessive disorder resulting in development of cerebellar ataxia and lymphoreticular neoplasms. Defect in?

Ataxia telangiectasia | ATM (ataxia telangiectasia mutated) and ATR proteins normally sense DNA damage and phosphorylate (and activate) p53

A congenital disorder of glycosylation. Absence of Golgi-located GDP-fucose transporter leads to absence of fucosylated ligands for selectins. Patients prone to life-threatening, recurrent bacterial infections and psychomotor and mental retardation. What is the tx?

Leukoacyte adhesion deficiency (II) | Tx: oral fucose

Acquired mild anemia characterized by the presence of Hg in urine due to hemolysis of red cells, particularly during sleep. The basic defect in this condition is somatic mutation in this gene. Which 2 proteins are deficient?

Paroxysmal nocturnal hemoglobinuria PIG-A (Phosphatidylinositol glycan class A) Proteins anchored by GPI missing: Decay accelerating factor CD59

In PNH, what 2 proteins are missing? What is their normal function?

Decay accelerating factor CD59Interact with components of the complement system to prevent hemolytic action. At night, drop in pH increases susceptibility to lysis by the complement system.

These conditions are a result of defects in synthesis of glycans in alpha-dystroglycan, which results in defective interaction with laminin-2 (merosin) in basement membrane.

Congenital muscular dystrophies | Walker-Warburg; Muscle-eye-brain disease, Fukuyama

How does Von Gierke's syndrome cause hyperuricemia?

Von Gierke's syndrome is characterized by deficiency in glucose-6-phosphatase which turns G6P (obtained from glycogenolysis) into free glucose. In this syndrome, accumulation of G6P leads to shunting of some G6P into the pentose phosphate pathway, increasing ribose-5-phosphate, and subsequent purine metabolism. Elevated purines eventually are catabolized into uric acid.

Developmental disorder affecting connective tissue and CNS. Increased risk of supravalvular aortic stenosis.

Williams syndrome | Absence of elastin

Characterized by increased bone density and in one form, RTA and cerebral calcification. Enzyme deficiency?

Osteopetrosis Carbonic anhydrase II in Chromosome 8 (HARD BONE = 8 letters) Osteoclasts secrete H+ into environment to increase solubility of hydroxyapatite. Within the cell, OH left is neutralized by H+ formed by normal carbonic anhydrase. In deficiency, osteoclast function is impaired.

Short limbs, normal trunk size, macrocephaly and skeletal abnormalities. Pattern of inheritance? Mutations in gene encoding ___?

AchonDroplasia Autosomal Dominant Fibroblast growth factor receptor 3 (FGFR3) (A tyrosine kinase receptor) Mutation involved substitution of Arg for Gly

Severe liver damage leads to hypouricemia and increased excretion of hypoxanthine and xanthine. Patients are at an increased risk of xanthine lithiasis.

Xanthine oxidase deficiency

This uncommon disease presents with progressive psychomotor retardation and a variety of physical signs. It is characterized by mutant GlcNAc phosphotransferases. Lack of GlcNAc 1-phosphate on mannose residues on many enzymes lead to secretion of these enzymes rather than being targeted to lysosomes.

I-Cell Disease

Mutation in genes leading to formation of abnormal Type II collagen, manifests as degeneration of joint cartilage and vitreous body of the eye.

Stickler Syndrome

Diseases in Biochemistry Flashcards

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