Trivia: Rare Genetic Conditions

Within the past decade, advances in genetic research have enabled scientists to pinpoint the defective genes responsible for some of the world's rarest diseases.

Hutchinson-Gilford Progeria Syndrome (HGPS) or progeria: Progeria is a genetic disorder that causes rapid and accelerated aging. The disease strikes one in four to eight million newborns, and only 100 or so cases have been documented in the medical literature. By six to 12 months, the child begins to lose hair and develop loose, aged looking skin. Other symptoms include growth failure, loss of body fat and muscle, stiff joints, hip dislocation, generalized atherosclerosis, cardiovascular disease, and stroke. Most children die from cardiovascular disease, and the average life expectancy for a progeria patient is 13, with a typical range of 8 to 21 years. Progeria is caused by a mutation in the LMNA (pronounced lamin-a) gene. As explained on the website of The Progeria Research Foundation, Lamin A protein forms the scaffold that holds the nucleus together. In progeria patients, defective Lamin A protein is believed to cause nuclear instability and premature aging. Progeria is not inherited; each case is caused by a new mutation in LMNA.

Fibrodysplasia Ossificans Progressiva (FOP): FOP is a genetic condition that affects one in two million people, or an estimated 2,500 individuals worldwide. In a process that has been called "turning to stone," the disease causes abnormal bone growth in the muscles, tendons, and ligaments, especially as a result of injury. The extra bone limits the person's mobility and deforms the body, eventually causing complete paralysis and death. Most people with FOP do not live past 30. FOP is caused by a mutation in the gene that codes for Actin Receptor Type IA (ACVR1). ACVR1 is part of the bone morphogenetic protein (BMP) signaling pathway, a system involved in the formation of the skeleton in embryos and the repair of the skeleton after birth.

Niemann-Pick Type C Disease (NP-C): NP-C is a genetic disease that prevents the normal absorption of low density lipoprotein-derived (LDL) cholesterol, commonly called "bad" cholesterol. This leads to the accumulation of cholesterol in the brain, liver, lungs, spleen, and bone marrow. NP-C is a progressive neurodegenerative disease that results in poor muscle control, impaired eye movements, slurred speech, and death, usually before the age of 10. NP-C is typically a pediatric disease, but adult onset may also occur. NP-C is linked to defects in the NPC1 and NPC2 (HE1) genes. Both genes code for proteins that move fats out of cellular structures called lysosomes.

Amish Lethal Microcephaly (ALM, aka Amish Microcephaly, MCPHA): Newborns with ALM have an extremely small head and underdeveloped brain. Other symptoms include a small lower jaw and chin (micrognathia), enlarged liver (hepatomegaly), seizures, difficulty maintaining body temperature, alpha-ketoglutaric acid in the urine (alpha-ketoglutaric aciduria), and elevated levels of acid in the blood and tissues during viral infections (metabolic acidosis). ALM is only found in the Old Order Amish population of Pennsylvania, and affects about 1 in 500 newborns in that group. Most babies with ALM die at four to six months of age, and the oldest lived to 14 months. ALM is caused by a mutation in the SLC25A19 gene, which disrupts a metabolic pathway important for prenatal brain development.

Menkes Disease (aka kinky hair disease): Menkes disease is caused by mutations in the Xq13.3 gene (ATP7A), which disrupt how copper is metabolized by the body. As a result, copper accumulates at abnormally low levels in the liver and brain, and abnormally high levels in the intestinal lining and kidneys. Symptoms usually appear at six to eight weeks of age, and include failure to thrive, seizures, floppy muscle tone, lower than normal body temperature, and osteoporosis. Menkes disease has major impacts on the brain, and causes extensive neurodegeneration of grey matter, along with brain arteries that are twisted and/or weak and prone to blockage and rupture. Menkes disease is also characterized by kinky hair that's steel-grey or colorless and breaks easily. Disease incidence is between one in 50,000 to one in 250,000. Menkes disease is an X-linked recessive condition, so more males are affected than females, since they only have one X chromosome. If Menkes disease is detected a few days after birth, copper injections and other treatments can improve the baby's survival rate and neurodevelopment. Most children affected by Menkes disease die before age 10.

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