Week 3 Disease Presentations

Question 1

Diseases presented in week 3

Answer 1

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)

Question 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

Answer 2

Familial Hypercholesteremia

Question 3

Cause of Familial Hypercholesteremia

Answer 3

Mutation on chromosome 1, 2, or 19

Question 4

Testing for Familial Hypercholesteremia / Genes affected

Answer 4

LDL-R Gene (required for uptake of LDL)

APOB Gene (produces apolipoprotein)

PCSK9 Gene (produces protein that degrades LDLr)

Question 5

Treatment for Familial Hypercholesteremia

Answer 5

Coumadin (Warfarin) – prevents blood clotting

Lipitor (atorvastatin) – lowers triglyceride

lomitapide – prevents VLDL formation in liver

Colestipol – fat sequester

Question 6

Types of Gaucher Disease

Answer 6

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

Question 7

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

Answer 7

Gaucher Type 1

Question 8

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

Answer 8

Gaucher Type 2 or 3

Question 9

Cause of Gaucher

Answer 9

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

Question 10

Treatment for Gaucher

Answer 10

Enzyme replacement therapy is the most common treatment

Question 11

Testing for Gaucher

Answer 11

Enzyme blood test

Genetic testing and molecular DNA analysis more accurate

Question 12

Cause of Phenylketoneuria

Answer 12

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

Question 13

Symptoms:

High level of Phenylalanine/Phenylpyruvate

Lower levels of Tyrosine

Intellectual disability

Seizures

Answer 13

Phenolketoneuria

Question 14

Test for phenylketoneuria

Answer 14

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

Question 15

Treatment for Phenylketoneuria

Answer 15

Diet

Lofenalac (protein supplement

Kuvan (sapropterin): increases tolerance to Phe

Question 16

Types of Muscular Dystrophy

Answer 16

Duchenne Muscular Dystrophy (DMD)

No dystrophin (frameshift)

Becker Muscular Dystrophy (BMD)

Shortened dystrophin (large deletion but no frameshift)

Question 17

Cause of Muscular Dystrophy

Answer 17

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.

Question 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

Answer 18

Muscular Dystrophy

Question 19

Testing for Muscular Dystrophy

Answer 19

EKG

Serum Creatine Kinase Levels

MLPA (genetic analsis)