Organelle-Based Diseases

Organelle-Based Diseases

Heredity & Genetics

Progeria

Cystic Fibrosis (CF)

Nucleus Disorder

Endoplasmic Reticulum Disorder

• A single gene (lamin -A or LMNA) creates the protein responsible for holding the nucleus together
• Without LMNA, the nucleus is unstable, and the cells begin prematurely aging.
• Within the first year, physical development is normal, then slows dramatically
• Motor development and intelligence remain normal
• Less than 1,000 US cases per year

• The most common childhood genetic disease in America
• A gene mutation of one protein of the ER disables the ability to regulate movement of salt in/out of cells
• Result: Thick, sticky mucus in the respiratory, digestive, and reproductive systems, as well as more salt in sweat
• CF is an inherited race disorder, most common in white people of Northern European ancestry
• Both parents must have at least one copy of the defective gene to pass it on to offspring
• 1:3,000 affect rate

• Symptoms
• Slowed growth, with below-average height and weight
• Narrowed face, small lower jaw, thin lips and beaked nose
• Head disproportionately large for face
• Prominent eyes and incomplete closure of the eyelids
• Hair loss, including eyelashes and eyebrows
• Thinning, spotty, wrinkled skin
• Visible veins
• High-pitched voice
• Some hearing loss
• Hip dislocation
• Severe progressive heart and blood vessel (cardiovascular) disease

Achondrogenesis

Golgi Apparatus Disorder

• Golgi apparatus is supposed to package proteins from the ER
• A defect in the protein (GMAP-210) responsible for the packaging structure in the the Golgi apparatus
• The proteins build up in the ER, which becomes swollen and affects the function of certain cells affecting the formation of bones and cartilage
• 1:60,000 affect rate

• Symptoms
• Shortened limbs/small body
• Infants born with achondrogenesis are born prematurely or stillborn
• Infant survivors can live only with intensive medical care

Tay-Sachs Disease

Lysosome Disorder

Treacher Collins syndrome (TCS)

Ribosome Disorder

• Lysosomes that are supposed to break down substances in the cell stop working
• In nerve cells, a certain lipid is supposed to be broken down by lysosomes with a specific enzyme known as Hex-A
• In Tay-Sachs disease, Hex-A is missing, so that lipid continually multiplies until it kills the cell and the central nervous system
• The defect starts in the fetus, but is undetected until ~6 months, when normal development begins to slow
• Affects those of Ashkenazi Jewish descent (~1:27 Jews in the USA)

• Symptoms:
• Normal development until ~6 months, then children develop seizures
• by two years, children start regressing
• Diminished mental function
• Unable to crawl, turn over, etc.
• Eventually they become blind, paralyzed, unresponsive, and mentally impaired
• Death usually results by age 5

• When ribosomes fail to create the right protein structure for one of 3 genetic markers, it triggers a self-destruct switch in certain cells that are involved in the development of facial bones & tissues
• It is unclear why TCS only targets the face
• TCS affects 1 in 50,000 people

Leber hereditary optic neuropathy

Mitochondria disorder

• Symptoms
• Underdeveloped facial bones, especially the cheek and jaw
• Cleft palate (hole in the roof of the mouth)
• Affected airway
• Downward slanted eyes
• Notched lower eyelids
• Vision and hearing loss
• It does not affect the intelligence
• TCS can be unnoticeable to very severe

• Mitochondria are supposed to create energy for the cell
• Four enzymes are responsible for converting oxygen and simple sugars to energy
• Mutations disrupt this process and creates vision loss, first in one eye, then the other a few months later

• Symptoms
• Vision loss begins in teens-twenties, affecting more males than females
• Men cannot pass on this disease; only women
• 1:50,000 births in Finland