Week 3 Disease Presentations Flashcards Preview

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Flashcards in Week 3 Disease Presentations Deck (19):
1

Diseases presented in week 3

Hypercholesterolemia

Autosomal Dominant

LDL receptor & endocytosis

(1/500)

 

Gaucher

Austosomal Recessive

Glucosylceramide metabolism lysosomal storage diseases 

(1/900 in Ashkenazi; 1/15 are carriers)

 

Phenylketonuria (PKU)

Autosomal Recessive

phenylalanine metabolism defect 

(1/15,000)

 

Duchenne Muscular Dystrophy 

X-linked recessive

dystrophin

(1/3500 males)

2

Symptoms:

Angina (chest pain)

Buildup of cholesterol in tissues (arcus cornealis -- eye halo, xanthomas -- fat builup under skin, xanthelasmata -- fat buildup in eye lids)

Calves cramping

 Stroke-like symptoms

Sores on toes that don’t heal

 

 

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Familial Hypercholesteremia

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Cause of Familial Hypercholesteremia

Mutation on chromosome 1, 2, or 19

4

Testing for Familial Hypercholesteremia / Genes affected

 

LDL-R Gene (required for uptake of LDL)

APOB Gene (produces apolipoprotein)

PCSK9 Gene (produces protein that degrades LDLr)

5

Treatment for Familial Hypercholesteremia

Coumadin (Warfarin) -- prevents blood clotting

Lipitor (atorvastatin) -- lowers triglyceride

lomitapide -- prevents VLDL formation in liver

Colestipol -- fat sequester

6

Types of Gaucher Disease

Type 1

most common

inherited Jewish genetic disease

non-neuronopathic (many neurons misfunction)

 

Type 2 and 3

neuronopathic

Type 2 is earliest, brain damage by 2 years old

Type 3 slower but die by 30 years old

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Symptoms: hepatosplenomegaly, anemia, thrombocytopenia (deficiency), fatigue, lung disease and bone abnormalities such as pain, fractures, and arthritis

Gaucher Type 1 

8

Symptoms: abnormal eye movements, seizures, and brain damage in addition to visceral symptoms of type 1

Gaucher Type 2 or 3

9

Cause of Gaucher

mutations in the GBA gene

GBA gene codes for the beta-glucocerebrosidase enzyme which breaks down glucocerebroside into a sugar and a simpler fat molecule

10

Treatment for Gaucher

Enzyme replacement therapy is the most common treatment

 

11

Testing for Gaucher

Enzyme blood test

Genetic testing and molecular DNA analysis more accurate

12

Cause of Phenylketoneuria

loss-of-function mutation of the Phenylalanine hydroxylase (PAH) gene

Accumulated Phe assemble into amyloid-like fibrils in the brain

Tyr is precursor for dopamine, epinephrine, norepinephrine

13

Symptoms: 

High level of Phenylalanine/Phenylpyruvate

Lower levels of Tyrosine

Intellectual disability

Seizures

Phenolketoneuria

14

Test for phenylketoneuria

Guthrie test 

Getting blood from heel in 24h and 7day baby

Detection of Tyr and Phe levels

Phe/Tyr ratio of 3 is high

 

Further testing: urinalysis, plasma amino acids, genetic testing

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Treatment for Phenylketoneuria

Diet

Lofenalac (protein supplement

Kuvan (sapropterin): increases tolerance to Phe

16

Types of Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD)

No dystrophin (frameshift)

 

Becker Muscular Dystrophy (BMD)

Shortened dystrophin (large deletion but no frameshift)

17

Cause of Muscular Dystrophy

Mutations in the gene that codes for the protein dystrophin

Dystrophin is a protein that connects the sarcolemma (muscle fiber membrane) to the cytoskeleton

OThe damage to the cell membrane creates openings for an influx of extracellular calcium. This influx in calcium activates proteases within the cell.

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18

Symptoms:

Progressive walking difficulty

Pseudohypertrophy (toddler age) – enlarged calf muscles due to an abundance of scar tissue in the abnormal muscle

 Cardiomyopathy (decreased integrity of the myocardium)

Possible small mental retardation

 

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Muscular Dystrophy

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19

Testing for Muscular Dystrophy

EKG

Serum Creatine Kinase Levels

MLPA (genetic analsis)