BI 211 Genetics for Healthcare: Ch. 10 Enzyme and Collagen Disorders

Gene expression is a result of..

DNA to RNA to protein

Types of Genetic Testing

Chromosome Scale (karyotypes)

Nucleotide Scale

Nucelotide Scale

looks at DNA sequence of INDIVIDUAL genes and is usually done to coding sequence to look for a particular sequence

How is the type of testing done determined?

information need

Reasons to Screen for Genetic Disorders

Suspected potential parent may be a carrier

Prenatal screening

Diagnose genetic syndrome after birth

Is the entire genome sequenced in genetic testing?

no

Enzymes

protein that catalyzes biological reactions

Deficient enzyme function results in..

excessive buildup of precursor substance and absent or low amounts of final products

Most enzyme disorders are..

autosomal recessive

Pleiotropy

A single gene having multiple effects on an individuals phenotype

Enzyme disorders exhibit ________.

pleiotropy

Do newborns typically have symptoms of enzyme disorders at birth?

NO

Why do newborns not typically show symptoms at birth?

maternal enzymes cross the placenta and eventually degrade after birth and are NOT replaced by the newborn

Sicne the enzymes cannot be replaced by the baby, what appears?

enzyme deficiency

Hyperaminoacidemias

one particular amino acid accumulates in the blood to toxic levels

Phenylketonuria (PKU)

an autosomal recessive disorder related to a defective recessive gene on chromosome 12 that prevents metabolism of phenylalanine to tyrosine

With hyperaminoacidemias, what is present?

excess phenylaline and deficiency in tyrosine

Where is PKU located?

PAH gene 12q24

Who is PKU most common in?

Northern European descent

After birth, what builds up in the blood?

excess phenylaline

Due to the excess phenylaline, what does the body do?

tries to metabolize phenylpyruvate and decreases the pH of blood

What issues does PKU cause in the development of a baby?

Developing nervous system and skin pigmentation as tyrosine is required for thyroid hormones, melanin, and neurotransmitter production

Signs and symptoms of PKU

Severe brain dysfunction

Severe cognitive deficiency (microcephaly, uncoordinated movement, seizures, tremors)

Severe growth deficiency

Lighter skin, hair, and eyes

Management of PKU

Strict dietary management to keep phenylalanine managed

Kuvan

Control of phenylalanine levels in the pregnancy of PKU women

PKU is part of what in each state? Why?

Newborn screenings due to the neurological issues

Kuvan

cofactor for enzyme that can help some cases of PKU

Lysosome

cell's recycling plant that degrades sugars, proteins, and lipids

What happens if lysosomal enzymes are lacking?

some compounds cannot be broken down

Gaucher Disease

autosomal recessive disorder on the GBA gene 1q21 that results in the lack of ability to break down glycolipid glycosylceramide

1 in _____ people are carriers of Gaucher Disease.

12

With Gaucher disease, what does the breaking down in the body?

macrophages

What is the issue with using macrophages?

They lack enzymes and cannot break down glycolipids, and leukocytes accumulate in tissues

Organs in Gaucher's Disease

enlarged with poor perfusion and greatly reduced function

Signs and Symptoms of Gaucher's Disease

Hepatosplenomegaly

Ostealgia

Osteoporosis

Anemia

Management of Gaucher Disease

Focus on managing symptoms with medications, splenectomy, enzyme replacement therapy

Cure for Gaucher Disease

HSCT (bone marrow transplant)

What is the issue with HSCT?

It is very expensive and dangerous

Epogen

treats anemia

Hurler Syndrome and Hunter Syndrome

both genes the disorder occurs on encode for enzymes required for mucopolysaccharide (MPS) degradation

Hunter Syndrome only occurs in..

males, as it is X-linked

Mucopolysaccharides

make up basement membranes in tissues

Basement membrane

Layer between epithelium and underlying connective tissue

MPS should be..

broken down and remade daily

Lysosomes of all cells have..

progressive MPS accumulatio

Signs and Symptoms of Hurler and Hunter Syndrome

None at birth

At 6 months, coarse facial features and poor physical growth

Limited cognitive development

Overproduction of mucus on airways

Cardiac and pulmonary obstruction

Without treatment of the obstructions, what will occur?

death in 5-10 years

Management of Hurler and Hunter Syndrome

Antibiotic treatment of respiratory infections

Weekly IV infusions with enzyme replacement therapy (ERT)

HSCT by age 2

Collagen

protein fibers which form connective tissue in the body and are key for strength and elasticity of many parts of the body

There are ____ major types of collagen located in different areas of the body and are encoded by different genes.

5

Collagen mutations are usually..

pleiotropic

Collagen Disorders

Osteogenesis Imperfecta

Ehler's Danlos Syndrome

Marfan Syndrome

Osteogenesis Imperfecta

easily fractured bones in response to minor trauma with no cure

What color are the sclera with OI?

blue-tinged

Management of Osteogenesis Imperfecta

physical therapy and safe, non-impact exercise

Ehlers-Danlos Syndrome

autosomal dominant disorder that is a group of 6 different inherited disorders

Pathophysiology of Ehler's Danlos

Atypical collagen is OVERLY stretchy and there is hyperextension of joints and skin, poor wound healing, and weakness of arteries/intestinal lining

Why is weak arteries and intestinal lining dangerous?

they can result in fatal hemmorhage and sepsis

Management of Ehlers-Danlos

no cure, education on injury prevention, and surgery due to decreased healing

Marfan's Syndrome

autosomal dominant disorder on 15q21 that results in mutated fibrillin

Why is mutated fibrillin an issue?

Fibrillin aids in collagen stretching under force and then rebounding into shape

Pathophysiology of Marfan Syndrome

connective tissue stretches out over time and do not return to shape, and it is pleiotropic

Signs and Symptoms of Marfan Syndrome

Tall, lanky

Long face, small chin

Long arms, long fingers

Spinal curvatures

Chest deformities

Heart problems

Myopia

Loose joints

Crowed teeth

Life expectancy for Marfan Syndrome

37 due to cardiovascular issues

Management of Marfan Syndrome

no cure, management of cardiovascular health and blood pressure, avoid contact sports