Rare Genetic Diseases and Disorders

Genetic diseases or disorders are caused due to abnormalities in the genetic material of an individual. Genetic disorders may be caused due to gene mutations (either in a single gene or multiple genes), chromosomal aberrations and rarely due to mutations in nonchromosomal DNA of mitochondria. Let’s see some of the rare genetic disorders.

Alkaptonuria: Alkaptonuria also known as black urine disease is caused due to disorder in the tyrosine metabolism of the body. It affects about 1 in 250,000 to 1 million people worldwide. Alkaptonuria is characterized by accumulation of alkapton or homogentisic acid (toxic tyrosine byproduct) in the blood, which is excreted in the urine. Urine of such patients becomes black when exposed to air. Presence of excess alkapton may result in osteoarthritis, heart disease, kidney stones and prostrate stones in men. Some of the symptoms of alkaptonuria are darkened skin and pigmented sclera (white part of eye). A patient of alkaptonuria should consume foods rich in vitamin C. One should avoid diets rich in tyrosine and phenylalanine.

Hereditary Angioedema (HAE): Hereditary angioedema, also known as Quincke's disease is caused due to abnormalities in the function of a protein 'C1 inhibitor'. Mutations within the C1-INH gene (C1NH) results in HAE. It affects the blood vessels, resulting in immune system problems. It is estimated to occur in 1 in 150,000 individuals. Common symptoms of hereditary angioedema include swelling of the arms, legs, eyes and throat, abdominal pain and airway blockage. Treatment is usually done by following medication, hormone treatment and administration of painkillers.

Kartagener's Syndrome: Kartagener's syndrome is a genetic disorder that causes chronic lung disease. About 1 in 30,000 people are affected with this syndrome. It is caused due to ciliary defect, which results in abnormal ciliary motion. Patients of Kartagener's syndrome are found to have defects in genes DNAH5 and DNA11. Symptoms of Kartagener's syndrome are difficulty in breathing, wheezing, chronic cough, sinusitis, bronchitis and infertility. Treatment of this syndrome is done by following medications, chest physiotherapy and sometimes by surgery intervention.

Krabbe Disease: Krabbe disease is caused due to disorder in the myelin sheath of the peripheral and central nervous system. It leads to destruction of the brain cells. About 1 in 100,000 births are affected with this genetic disorder. Usually, children with Krabbe disease die before the age of 2. Symptoms of this disease are vomiting, seizures, mental retardation, deafness and blindness. Bone marrow transplantation has shown to be in some cases of this disease. Recent studies have found out that newborn babies with Krabbe disease can be treated with the help of stem cells from umbilical cord blood storage.

Mucopolysaccharidosis VI: Mucopolysaccharidosis VI is a genetic disease that affects about 1 in 300,000 births. It is caused due to the deficiency of N-acetylgalactosamine 4-sulfatase (arylsulfatase B) activity that is responsible for catabolism of complex carbohydrates (polysaccharides). This results in accumulation of dermatan sulfate in some of the organs such as skeleton, lung, heart valves, spleen and liver. Symptoms of Mucopolysaccharidosis VI are short stature, mental retardation, respiratory diseases, deafness and blindness. Treatment is done by following enzyme replacement therapy along with regular medical care.

Tuberous Sclerosis (TS): Tuberous sclerosis is formerly known as Bourneville's disease. It is a rare genetic disorder and affects about 1 in 10,000 people throughout the world. About 80% of the cases of TS are due to mutations in two specific genetic loci TSC1 and TSC2. Tuberous sclerosis is caused due to growth of tuber-like tumors in brain, lungs, heart and kidneys. Common symptoms of TS include skin lesions in the nose and cheek area, periungual fibroma, epileptic seizures, behavioral problems, lung and kidney diseases and mental retardation. Symptom of epileptic seizure can be treated by surgically removing the tubers that are responsible for epilepsy. Studies are going on for drug therapies of TS.

Unfortunately, there is no cure for genetic disorders. In fact, they are a major challenge for medical researchers all over the world. Researches on cloning of genes, gene therapy, suppression of genes responsible for causing genetic diseases and enzyme replacement are ongoing to find ways to treat rare genetic diseases and disorders.