Disease Cause Semester 1

Question 1

1. Primary Cause of Duschene/Becker Muscular Dystrophy?
2. Inheritance Pattern?

Answer 1

1. Loss of function/ impaired function mutations in the Dystrophin protein
2. X-Linked Recessive

Question 2

1. Primary cause of Tay-Sachs Disease?
2. Inheritance Pattern?

Answer 2

1. Mutation in HEXA gene which encodes for beta- hexoaminadase A, a lysosomal enzyme. Leading to accumulation of GM₂ ganglioside
2. Autosomal Recessive, a Sphingolipidoses

Question 3

1. Primary cause of Metachromatic Leukodystrophy?
2. Inheritance Pattern? Disease Classification?

Answer 3

1. Deficiency in ARSA gene which encodes Arylsulfatase A a lysosomal enzyme, leading to accumulation of sulfatides.
2. Autosomal Recessive, a Sphingolipidosis

Question 4

1. Primary Cause of Cystic Fibrosis?
2. Inheritance Pattern?

Answer 4

1. Mutation in the CFTR genes, encodes for a ATP-gated Chloride Channel.
2. Autosomal Recessive

Question 5

1. Primary Cause of I-Cell Disease?
2. Inheritance Pattern? Disease Classification?

Answer 5

1. Deficiency in the Golgi prevents formation of the M6P (mannose-6 phosphate tag), leads to deficiency in almost all lysosomal enzymes.
2. Recessive defects patients do not reproduce. A Mucolipidoses

Question 6

1. Primary Cause of Hurler Syndrome?
2. Inheritance Pattern? Disease Classification?

Answer 6

1. Defective alpha-L-Iduronidase enzyme, leads to accumulation of Heparan/dermatan sulfate
2. Autosomal Recessive, a type of Mucopolysaccharidosis

Question 7

1. Primary cause of Hunters Syndrome?
2. Inheritance Pattern? Disease classification?

Answer 7

1. Defective Iduronate-2-sulfatase enzyme, leads to accumulation of Heparan/dermatan sulfate
2. X-linked, a type of Mucopolysaccharidosis

Question 8

1. Primary Cause of Sickle Cell Disease?
2. Inheritance Pattern?

Answer 8

1. Mutated Beta-globin gene, leading to accumulation of Hemoglobin S leading to sickle-shaped erythrocytes. Normal individuals have Hemoglobin A
2. Autosomal Recessive

Question 9

1. Primary Cause of Achondroplasia?
2. Inheritance Pattern? Disease classification?

Answer 9

1. Mutation in the FGFR3 gene, encodes Fibroblastic Growth Factor 3
2. Autosomal Dominant (Structural Gene), Collagen Disorder

Question 10

1. Primary Cause of Marfan’s Syndrome?
2. Inheritance Pattern? Disease Classification?

Answer 10

1. Mutation in FBN1, encodes for Fibrillin an elastin scaffold protein
2. Autosomal Dominant (Structural Gene), Collagen Disorder

Question 11

1. Primary Cause of Osteogenesis Imperfecta?
2. Inheritance Pattern? Disease Classification?

Answer 11

1. Mutations is Type I Collagen, range of phenotypes from mild -> lethal , always blue sclera (white of the eyes)
2. Autosomal Dominant (structural), Collagen Disorder

Question 12

1. Primary Cause of Ehlers-Danlos Syndrome?
2. Inheritance Pattern? Disease Classification?

Answer 12

1. Primarily caused by Type V Collagen mutation, a fibrillar collagen
2. Autosomal Dominant, Collagen Disorder

Question 13

1. Primary Cause of Alport Syndrome?
2. Inheritance Pattern? Disease Classification?

Answer 13

1. Mutation of Type IV Collagen (Sheet/Network collagen of the basal lamina)
2. Autosomal Dominant, Collagen Defect

Question 14

1. Primary Cause of Goodpasture Syndrome?
2. Inheritance Pattern? Disease Classification?

Answer 14

1. An Autoimmune disease that targets antibodies at Type IV Collagen
2. Autoimmune Environmental/Genetic Predisposition, Autoimmune Disorder

Question 15

1. Cause of Epidermolysis Bullosa?
2. Inheritance Pattern? Disease Classifiction?

Answer 15

1. Dystrophic EB -> Mutation in Type VII Collagen (Anchoring Collagen) Most severe at lowest layer. Severity increases as you go deeper in the epidermis.
2. AD/AR, recessive more severe, Collagen Disorder

Question 16

1. Primary Cause of Pemphigus Vulgaris?
2. Inheritance Pattern? Disease Classification?

Answer 16

1. Caused by auto-antibodies against desmosomal Cadherins
2. Autoimmune Disorder, environmental/genetic predisposition.

Question 17

1. Primary Cause of Charcot-Marie-Tooth Neuropathy?
2. Inheritance Pattern? Disease Classification?

Answer 17

1. Caused by lack of Connexin-32 protein a gap junction protein
2. X-linked and Autosomal Dominant forms, Peripheral Neuropathy

Question 18

1. Primary Cause of Bullous pemphigoid?

Answer 18

Auto-antibodies against hemidesmisomal protein

Question 19

1. Acute Pancreatitis Symptoms?
2. Pathogenesis?
3. Diagnosis? What to look for basically?

Answer 19

1. Abdominal Pain, Tachycardia, Nausea/Vomiting
2. Autodigestion of Pancreatic tissue by activated pancreatic enzymes
3. Increase amylase concentration in plasma and saliva

Question 20

1. What is the primary cause of De Vivo Disease?
2. Inheritance Pattern?
3. Symptoms?

Answer 20

1. Defect in the GLUT1 Transporter
2. Autosomal Dominant
3. Refractory Infantile Seizures, Microcephaly, Motor Dysfunction

Question 21

1. Primary Cause of Fanconi Bickel Syndrome? (AKA Glycogen Storage Disease XI)
2. Inheritance?
3. Symptoms?

Answer 21

1. Defect in GLUT2 Transporter
2. Autosomal Recessive
3. Hepatomegaly, Hyperglycemia, Failure to Thrive,

Question 22

1. Primary Cause of Beriberi?
2. Symptoms in Adults?
3. Symptoms in Children?

Answer 22

1. Severe Vitamin B1 Deficiency (Thiamine) in areas where polished rice is major diet.
2. Wet Beriberi- affects the cardiovascular system
   Dry Beriberi- affects the nervous system
3. During breast feeding by Vitamine B1 deficient mothers, tachycardia, vomiting, convulsions.

Question 23

1. Primary cause of Wernicke-Korsakoff Syndrome?
2. Symptoms?

Answer 23

1. Vitamin B1 (Thiamine) Deficiency due to chronic alcoholism, ethanol blocks thiamine absorption.
2. Damage to medial dorsal nucleus, mammillary bodies
   Confusion, personality changes, encepholopathy

Question 24

1. Primary Cause of Pellagra?
2. Symptoms?

Answer 24

1. Dietary Vitamin B3 Deficiency (NAD+)
2. Symptoms 3Ds -> Diarrhea, dermatitis, dementia, also Glossitis (tongue inflammation)

Question 25

1. Primary Cause of **Hartnup Disease?** 2. Symptoms?

Answer 25

1. **Defect in absorption of non-polar amino acids including Tryptophan, a precursor for Vitamin B3** 2. Similar presentation as Pellagra **(Diarrhea, Dermatitis, Dementia)**, also **Aminoaciduria**

Question 26

Vitamin B2 Deficiency (FAD, Flavin) Symptoms?

Answer 26

**UV Light Sensitivity**, Burning Eyes, Corneal Vascularization (Bloodshot eyes)

Question 27

1. Cause of **Arsenic Poisoning**? 2. Symptoms?

Answer 27

1. **Arsenic is a suicide inhibitor of the Pyruvate dehydrogenase complex**. Forms a stable bond with the SH- of **Lipoic Acid** 2. **Garlic Breath**, **Skin pigmentation changes**, Skin Cancer **Fun Fact**Arsenic found in ground water and pesticides

Question 28

1. PDH Deficiency Cause/Inheritance? 2. Symptoms 3. Treatment

Answer 28

1. **X-linked dominant deficiency** in **E1 subunit** of Pyruvate Dehydrogenase Complex 2. Neurodegeneration, Lactic Acidosis, Early death 3. Treatment is a ketogenic diet

Question 29

1. Primary Cause of **Lactic Acidosis**?

Answer 29

1. **Usually caused by high concentration of NADH**, prevents Pyruvate oxidation and directs it towards Lactate. Normal Lactate conc. (0.5-2.2 moles/L) Caused by high alcohol consumption (increases NADH), hypoxia of any tissue (no oxygen -> anaerobic), Electron Transport Chain defects/inhibitors, Vitamin B1 deficiency, Mitochondrial disorders. **All of these cause issues with Pyruvate usage and body has to get rid of Pyruvate so lactate dehydrogenase is the path to go. **

Question 30

1. Symptoms of **Glucose 6-Phosphate Dehydrogenase Deficiency**? 2. Inheritance?

Answer 30

1. Increased oxidative stress, reduced NADPH production, **RBC Hemolysis due to Heinz Body (denatured hemoglobin) accumulation.** 2. X-Linked Recessive, Absence of G6PD enzyme. 3. Fava Beans can cause oxidative problems in these individuals.

Question 31

1. Primary Cause of **Essential Fructosuria**? 2. Symptoms? 3. Inheritance Pattern?

Answer 31

1. Caused by deficiency in **Fructose Kinase Enzyme**. 2. **Excretion of Fructose in urine**, Recurrent UTIs and Dehydration 3. **Autosomal Recessive**

Question 32

1. Primary Cause of **Hereditary Fructose Intolerance**? 2. Symptoms? 3. Inheritance Pattern?

Answer 32

1. Deficiency in **Aldolase B Enzyme**. Accumulation of Fructose 1-Phosphate 2. When fructose introduced into diet, **Hypoglycemia, Metabolic Acidosis, nausea/vomiting. ** 3. Autosomal Recessive

Question 33

1. Primary Cause of **Non-Classical Galactosemia**? 2. Symptoms? 3. Inheritance Pattern?

Answer 33

1. Deficiency in **Galactokinase (GALK)** Galactose -> Galactose 1-Phosphate 2. **Early Onset Cataracts first few months of life (Cloudy Lens)** 3. Autosomal Recessive, begins with consumption of breast milk

Question 34

1. Primary Cause of **Classical Galactosemia (GALT)**? 2. Symptoms? 3. Inheritance Pattern?

Answer 34

1. Deficiency in **GALT Enzyme**. Galactose 1-Phosphate -> Glucose 1-Phosphate 2. Accumulation of Galactose1Phosphate causes Osmotic Damage, **Cataracts**, **Liver damage**, Brain damage, Hypoglycemia 3. Autosomal Recessive

Question 35

1. Primary Cause of **Essential Pentouria**? 2. Symptoms? 3. Inheritance Pattern?

Answer 35

1. Deficiency in **Xylitol Dehydrogenase Enzyme**. **L-Xylulose -> Xylitol** 2. **Excretion of large quantities of L-Xylulose in urine.** 3. Autosomal Recessive

Question 36

Cause, pathogenesis, and symptoms of **Hartnup Disease**?

Answer 36

Question 37

Cause, pathogenesis, and symptoms of **Cystinuria**?

Answer 37

Question 38

1. Primary Cause of **Ornithine transcarbamylase deficiency**? 2. Symptoms? 3. Inheritance pattern?

Answer 38

1. Defect in **Ornithine transcarbamylase (OTC) enzyme**

Question 39

1. Primary cause of **Carbamoyl Phosphate Synthetase 1** deficiency? 2. Symptoms? 3. Inheritance Pattern?

Answer 39

1. Defect in **CPS1 enzyme**.

Question 40

Cause, symptoms, and inheritance of **Albinism**?

Answer 40

Question 41

Cause, symptoms, inheritance of **Histadinemia**?

Answer 41

Cause: • **Deficiency of Histidase** Phathobiochemistry: • Histidine undergoes transamination, forms imidazole pyruvate, imidazole lactate, imidazole acetate Symptoms: • **Most patients remain asymptomatic** • May lead to hyperactivity, speech impediment, developmental delay, intellectual disability Diagnosis: • **Sweat urocanate levels decreased, FIGLU excretion decreased** • Increased levels of histidine, histamine and imidazole

Question 42

Cause, Symptoms, Inheritance of **Homocystinuria**?

Answer 42

Symptoms Symptoms: • **Homocysteine in urine,** • Tall stature • Kyphosis • **lens subluxation (downward and inward)** • **Intellectual disability** • Osteoporosis • Thrombosis and atherosclerosis (stroke and MI)

Question 43

Cause, Symptoms, Inheritance of **Proprionic acidemia**?

Answer 43

Question 44

Cause, Symptoms, Inheritance of **Methylmalonic acidemia**?

Answer 44

Question 45

Cause, Symptoms, Inheritance of **Maple Syrup Urine Disease (MSUD)**?

Answer 45

Cause: • partial or complete loss of **Branched chain a- ketoacid dehydrogenase** • **Autosomal recessive** Phathobiochemistry: • Accumulation of Leucine, Isoleucine and Valine - toxic effect on the brain • Hypoglycemia – due to decreased acetyl co-A • Hyperammonemia - accumulation of CoA derivatives of organic acids inhibit the N-acetylglutamate (activator of CPS1 in liver) Classification: • Classical MSUD – little or no enzyme activity – infants show symptoms within first few days • Intermediate & intermittent forms – some enzyme activity (3-15 %) – milder disease and later onset • Thiamine-responsive form – large doses of thiamine help to increased enzyme activity

Question 46

Cause, Symptoms, Inheritance of **Isovaleric acidemia**?

Answer 46

Question 47

Cause, Symptoms, Inheritance of **Alkaptonuria aka Black Urine Disease**?

Answer 47

Symptoms: • **Homogentisic aciduria** • Urine turns black after exposure to air • Ear wax exposed to air turns red or black • Ochronosis (pigmentation) of cartilage leading to osteoarthritis – precocious lower back pain, and large joint arthritis • **May be symptomless until aged 40+: **arthritis, but disease may be recognized earlier by black-soiled diapers

Question 48

Cause, Symptoms, and Inheritance of **Type 1 Tyrosinemia**?

Answer 48

Question 49

Cause, Symptoms, and Inheritance of **Type 2 Tyrosinemia**?

Answer 49

Question 50

Cause, Symptoms, Inheritance of **Classic Phenylketouria (PKU)**?

Answer 50

Cause: • deficiency of **Phenylalanine Hydroxylase** • **Autosomal recessive** defect in PAH gene (1 in 10,000 Caucasians) Phathobiochemistry: • **accumulation of phenylalanine** (PA) → alternative phenylalanine metabolism → formation of metabolites: phenylacetate, and phenylpyruvate • deficiency of **tyrosine** • deficiency of neurotransmitters, melanin

Question 51

Cause, Symptoms, and Inheritance of **Non-PKU Hyperphenylalaninemia (aka Malignant PKU)**

Answer 51

Cause: • deficiency of **Dihydropteridine reductase (BH4)** • **Autosomal recessive** Phathobiochemistry: • BH4 is required for Phenylalanine hydroxylase, Tyrosine hydroxylase and Tryptophan hydroxylase (synthesis of Serotonin, Dopamine, Epi and NE) • High levels of Prolactin (Dopamine tonically inhibits Prolactin secretion by inhibition of lactotrophs)

Question 52

Cause, Symptoms, Inheritance of **Chronic Granulomatous Disease**?

Answer 52

**Deficiency in NADPH Oxidase**, can’t make Super Oxide so impaired respiratory burst. **X-linked recessive**. **Increased infections by catalase positive organisms**

Question 53

Cause, symptoms, and inheritance of **Myeloperoxidase Deficiency**?

Answer 53

Deficiency in **Myeloperoxidase**, makes H202 (bleach), increased risk of **candida (fungal) infections**. Autosomal Recessive.