Genetic Disorders /Diseases

Presenter: Psyche Arnoco

• Congenital Adrenal Hyperplasia

• Galactosemia

Congenital Adrenal Hyperplasia (CAH)

Congenital - present from birth

Adrenal - denoting a pair of ductless glandssituated above the kidneys.

Hyperplasia - the enlargement of an organ ortissue caused by an increase in thereproduction rate of its cells, often as an initialstage in the development of cancer.

CAH

- is a collection of inherited conditions that affect the body’s adrenal glands, which are the cone-shaped organs that sit on top of the kidneys.

adrenal glands•Located at the top of each kidney•produce hormones that help the body control blood sugar, burn protein and fat, react to stressors like a major illness or injury, and regulate blood pressure.

• What are hormones?Hormones are chemical messengers that are secreted

directly into the blood, which carries them to organs and tissues of the body to exert their functions. There are many types of hormones that act on different aspects of bodily functions and processes.

• What is an enzyme?a substance that acts as a catalyst in living organisms,

regulating the rate at which chemical reactions proceed without itself being altered in the process.

Hormones in the adrenal glands that are affected:

Cortisol

• Involved in the regulation of metabolism in cells

• also help us regulate various stressors in the body

Aldosterone

• affects the body's ability to regulate blood pressure.

• It sends the signal to organs, like the kidney and colon, that can increase the amount of sodium the body sends into the bloodstream or the amount of potassium released in the urine.

Hormones in the adrenal glands that are affected:

Androgens

• Androgens are a group of chemically related sex steroid hormones. Steroids are a special kind of fat molecule with a four-ringed, carbon atom backbone or core, like their cholesterol predecessor.

• Say the word androgen and most people think male. Indeed, they are dubbed the male hormones mainly because males make and use more testosterone and other androgens than females

• In CAH, the body is missing an enzyme (chemical substance) that helps the adrenal glands to release the hormones. As a result hormones cannot be produced.

• The brain then detects low level of hormones and tries to send signals to the adrenal gland to work harder. However, this mechanism is futile because of the absence of the enzyme needed to stimulate the adrenal glands to release the hormone

• As a result, the adrenals grow in size.

• With the adrenals working harder, but still unable to make the hormones, more of the sex hormones are made instead.

• The missing enzyme is 21-Hydroxylase- make cortisol and aldosterone in the adrenal glands

• The job of this enzyme is to help make cortisoland aldosterone in the adrenal glands so they can be released when the body needs them.

Causes of CAH

• In 95 percent of cases, the enzyme lacking in congenital adrenal hyperplasia is 21-hydroxylase. CAH may sometimes be called 21-hydroxylase deficiency.

• CAH is passed along in an inheritance pattern called autosomal recessive. Children who have the condition have two parents who either have CAH themselves or who are both carriers of the genetic mutation that causes the condition.

• What causes the 21-hydroxylase enzyme to

be absent or not working correctly?

Genes tell the body to make various enzymes.

People with CAH have a pair of genes that do

not work correctly. Because of the changes in

this pair of genes, the 21-OH enzyme either

does not work properly or is not made at all.

A child with classic CAH may experience:

• A lack in the production of cortisol in both the

salt-losing and simple-virilizing forms.

• A lack in the production of aldosterone in the salt-

losing form.

• Excess production of the male sex hormones

(androgens such as testosterone).

two major types of congenital adrenal hyperplasia:

• Classic CAH. This more-severe form of the disease is usually detected in infancy.

- Salt-wasting

- Simple-virilizing

• Nonclassic CAH. This milder and more common form may not become evident until childhood or early adulthood.

Salt-wasting Classic CAH

Salt-wasting classic CAH

• 75% of classic CAH cases.

• This is the most severe form. Signs of salt-wasting CAH

usually begin within the first few weeks of life.

• These signs include:

* Poor feeding * Sleeping longer or more often

* Tiredness * Vomiting

* Diarrhea *Irritability

* Rapid heart rate * Male-like genitals in females

* Weight loss

Simple-virilizing classic CAH

• 25% of classic CAH cases.

• less severe than salt-wasting CAH, but more severe than non-classic CAH.

• Signs begin before birth.

• These signs differ between males and females, which usually become apparent during childhood due to early puberty.

• Early signs of simple-virilizing CAH include:– Enlarged clitoris (it may look like a small penis)

– Labia that are fused together (they may resemble a scrotum)

– Small testicles

Simple-virilizing Classic CAH

Non – classic CAH

Non-classic CAH is much less severe than classic forms of CAH. Signs of non-classic CAH can begin in childhood, adolescence, or adulthood. Both males and females with non-classic CAH may show signs of early puberty.

• later signs and symptoms often include:

- Irregular or absent menstrual periods

- Masculine characteristics such as facial hair, excessive body hair and a deepening voice

• In both females and males, signs and symptoms of nonclassicCAH also may include:

- Early appearance of pubic hair

- Rapid growth during childhood, but shorter than average final height

Mode of inheritance

To have an autosomal recessive

disorder, you inherit two

mutated genes, one from each

parent. These disorders are

usually passed on by two

carriers. Their health is rarely

affected, but they have one

mutated gene (recessive gene)

and one normal gene (dominant

gene) for the condition. Two

carriers have a 25 percent

chance of having an unaffected

Frequency

The prevalence of CAH

is approximate1y

estimated as 1 out of 10,

000 to 18, 000 live

births.

Treatment for CAH

• The main treatment for classic CAH is a drug called ‘hydrocortisone’ (also called ‘cortisone’), taken in pill form. This medication replaces the cortisol that your baby cannot make on his or her own.

• Surgery for girls with classic CAHGirls who are born with an enlarged clitoris or changes to the labia have the option of surgery to change their outer genitals to a more female appearance.

• Treatment to prevent short statureYour doctor may take periodic X-rays to check your child’s ‘bone age’. This allows your doctor to tell whether your child is growing at too rapid a rate.

• Treatment for early puberty

Children who show changes of puberty at a young age are sometimes treated with medications that lower the amount of androgen hormones.

• Additional treatment for classic CAH – salt-wasting form

- need to take an additional medication called Florinef(is a ‘salt-retaining’ drug that replaces the aldosteroneabsent in children with salt-wasting CAH)

- follow a food plan that contains more salt than usual

• Children and adults with nonclassic CAH usually need less medication than children with classic CAH.

Treatment for CAH

Review

• CAH is an inherited disorder that affects the adrenal gland.

• CAH is caused by a deficiency of an enzyme (adrenal steroid 21-hydroxylase) necessary for the synthesis of two vital hormones, cortisol and aldosterone, by the human body. In its severest form, classical CAH results in the uncontrolled loss of salt and fluids from the body, a condition which, if undetected, can lead to adrenal crisis and death.

• Classical, severe CAH can cause genital anomalies in affected females, with baby girls occasionally misidentified as boys

Galactosemia

What is galactosemia?

Galactosemia is a family of genetic disorders that result from compromised ability to metabolize the sugar galactose; the term “galactosemia” literally means too much galactose in the blood. The different types of galactosemia include:

• Classic and clinical variant galactosemia (aka Type I galactosemia)

• Duarte variant galactosemia

• Galactokinase deficiency (aka Type II galactosemia)

• Epimerase deficiency (aka Type III galactosemia)

Galactose

- is a simple sugar, which belongs to simple carbohydrates.

Galactose is composed of the same elements as glucose, but

has a different arrangement of atoms.

- From the Greek gala = milk, and -ose, which denotes sugar.

Function:

- provide 4.1 kilocalories per gram of energy, which is about

the same as sucrose.

- bind to glucose to make lactose (in breast milk), to lipids to

make glycolipids, or to proteins to make glycoproteins (for

example, in cell membranes).

Sources of Galactose

• lactose from milk and yogurt, which is

digested to galactose and glucose

• certain yogurts, cheeses, creams, ice creams

and other foods artificially sweetened with

galactose

• Plain natural foods (fruits, vegetables, nuts,

grains, fresh meats, eggs, milk) usually contain

less than 0.3 g galactose per serving

Galactosemia is an autosomal recessive disorder

caused by deficient or absent activities of one

of the three enzymes involved in the galactose

metabolic pathway:

- galactokinase

- galactose-1- phosphate uridyltransferase

- and UDP-galactose 4’-epimerase

• The classical and most severe form is caused by a deficiency of the enzyme galactose-1-phosphate uridyl transferase (GALT).

• The gene for galactose-1-phosphate uridylyltransferase ( GALT gene ) is located on the short arm of chromosome 9, in the region 9p13.

• Galactose-1-phosphate uridylyltransferase(GALT) is an enzyme responsible for converting ingested galactose to glucose.

Preventive Measure Signs and Symptoms Early symptoms may include:

• Jaundice(yellowing) of the skin and whites of the eyes

• Vomiting

• Poor weight gain

• Low blood sugar (hypoglycemia)

• Feeding difficulties

• Irritability

• Lethargy

• Convulsions

Later signs and symptoms may include:

• Opaque lenses of the eyes ( Cataract )

• Enlarged liver, enlarged spleen

• Mental retardation

• Cirrhosis liver failure & Kidney problems

Diagnosis

Prenatal Testing A doctor can determine during a woman’s pregnancy whether her baby has galactosemia through:

a. amniocentesis . This procedure involves using a needle to withdraw a sample of amniotic fluid from the womb, and then examining the cells.

b. chronic villus sampling or CVS

c. NewBorn Screening -Babies are tested for Galactosemia at birth using a tiny blood sample taken from the baby’s heel, the test for low level of the GALT enzyme.

This is how the galactosemia happen when there is no GALT that would

binds to the galactose which facilitate the conversion of galactose to

glucose.

Treatment

• No treatment or cannot be cure but with maturation most children develop another enzyme capable of metabolizing galactose.

• As a consequence, they are able to tolerate galactose as they mature.

• Dietary restriction, avoid food and drinks containing galactose like milk, cheese, legumes (dried beans), fermented soy products, organ meat and hydrolyzed proteins.

Frequency

Classic galactosemia occurs

in 1 in 30,000 to 60,000

newborns. Galactosemia

type II and type III are less

common; type II probably

affects fewer than 1 in

100,000 newborns and type

III appears to be very rare.

Mode of inheritance

To have an autosomal recessive

disorder, you inherit two

mutated genes, one from each

parent. These disorders are

usually passed on by two

carriers. Their health is rarely

affected, but they have one

mutated gene (recessive gene)

and one normal gene (dominant

gene) for the condition. Two

carriers have a 25 percent

chance of having an unaffected

Review

• The condition is caused by a mutation in the gene that codes for the GALT enzyme.

• The enzymes involved is galactose-1-phosphate uridyl transferase (GALT) and in galactosemia, this enzyme is either defective or missing. When this happens, an infant is unable to convert the galactose into glucose which causes galactose to accumulate in the blood. This can lead to serious problems such as liver enlargement, kidney failure, brain damage and cataracts. Left untreated, this condition kills as many as 75% of sufferers.

• http://www.mayoclinic.org/diseases-conditions/congenital-adrenal-hyperplasia/symptoms-causes/dxc-20309080

• http://www.babysfirsttest.org/newborn-screening/conditions/congenital-adrenal-hyperplasia

• http://www.galactosemia.org/understanding-galactosemia/