Section 6 - Genetic & Pediatric Diseases

T/F: Hereditary diseases do not need to be present at birth, but are passed from parent to offspring.

True

What is the biggest risk factor for disorders from chromosomal abnormalities?

Maternal age

What cellular components are altered/compromised in autosomal dominant diseases?

Structural proteins

Membrane receptors

What kind of onset does an autosomal dominant disorder tend to have?

Delayed onset

What is typically altered in autosomal recessive disorders?

Enzymes

What kind of onset is associated with autosomal recessive disorders?

Early onset

What are the autosomal dominant disorders discussed?

Marfan, EDS, Familial Hypercholesterolemia

What is affected by Marfan syndrome?

Fibrillin - elastic fibers of ligaments and aorta

What are some key characteristics of Marfan syndrome?

Slender/long limbs

Bilateral lung subluxations

Ruptured arota

Atlantoaxial instability

In dural ectasia in Marfan Syndrome, where is this most commonly found in the spine?

Lumbar

What is affected by EDS?

Defective collagen

What is the popular characteristic of EDS?

Hyperextensible skin

Hypermobile joints

Vessel fragility

What disease is similar to EDS but not the same?

Benign joint hypermobility syndrome

What demographic has a higher rate of benign joint hypermobility syndrome?

Children

What are the physiologic features of Familial Hypercholesterolemia?

Increased LDL in plasma

Increased vascular deposits

What is a common feature of familial hypercholesterolemia?

Xanthomas

Which is more severe - homozygous or heterozygous hypercholesterolemia?

Homozygous - childhood onset and lethal coronary artery disease

What gene is mutated in cystic fibrosis?

CFTR - leads to decreased chloride ion transportation

What organs are primarily affected by cystic fibrosis?

Lungs and pancreas

What is the most common cause of death with cystic fibrosis?

Cor pulmonale

What gene is mutated in PKU?

Phenylalanine hydroxylase

What are the key features of PKU?

Decreased skin and hair pigmentation

What is the primary feature of Alkaptonuria?

Dark urine

What enzyme is mutated in galactosemia?

Glactose-1-Phosphate Uridyltransferase

What is the key feature of Galactosemia?

Failure to thrive

What are key features of lysosomal storage diseases?

CNS damage

Early onset

Debilitating or fatal

What are the lysosomal storage diseases discussed?

Tay-Sachs

Gaucher

Mycopolysaccharidosis (Hurler/Hunter Syndromes)

What enzyme is mutated in Tay-Sachs?

Hexosaminidase A enzyme

What cannot be metabolized with Tay-Sachs?

G_M2 gangliosides

What are the key features of Tay Sachs?

Cherry-red central macula

Gangliosides accumulate in neurons/glial cells

What population is primarily affected by Tay-Sachs?

Ashkenazi Jews

What enzyme is affected by Gaucher?

Glucocerebrosidase

What systems are affected by Gaucher?

Liver, spleen, and bone marrow

What disease should be associated with osteonecrosis and pancytopenia?

Gaucher

Why is Type I Gaucher less severe?

Does not cause CNS damage

Also associate with Ashkenazi Jews

What is a key feature of Gaucher disease?

Erlenmeyer flask deformity

What enzyme is affected in Mucopolysaccharidosis?

ECM breakdown enzymes

What accumulates in MPS?

GAGs - heparan sulfate and dermatan sulfate

What are some key features of MPS?

Clouding of cornea, joint stiffness, heart valve disease, Gargoylism

T/F: Hurler Syndrome is more severe than MPS.

True

What are some features of Hurler Syndrome?

Corneal clouding and heart attacks

What are some key feautres of Hunter Syndrome?

no corneal clouding, possible valve disease, less severe!

What enzyme is affected by Hurler Syndrome?

alpha-L-iduronidase

Autosomal recessive

What enzyme is affected by Hunter syndrome?

L-iduronate sulfatase

X-linked

Where does glycogen tend to accumulate?

Liver, skeletal muscles, heart