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AUTUMN 2024 InTouch | 15 FRIEDREICH ATAXIA Continued over ... Caption needed ... Progressive skeletal deformities can occur due to weakness and atrophy of supporting muscles. Scoliosis (an abnormal curvature of the spine) can become severe enough to restrict respiratory function. Spinal bracing may be required, and, in more severe cases, spinal fusion surgery. An orthopaedic specialist is essential in monitoring the scoliosis. Foot deformities such as pes cavus (abnormally high arches), hammer toes, and foot inversion (turning inward) are common in FA. These usually do not pose a problem in themselves, though if issues do arise, bracing or surgery can be beneficial. The muscles controlling speech can be affected, resulting in slow and slurred speech (dysarthria). Similarly, there can be incoordination of the muscles that control swallowing, which can increase the risk of choking and aspiration. Speech therapists can help with communication skills and teach compensatory strategies for improving swallowing safety if needed. Conditions associated with Friedreich Ataxia Cardiac problems develop in approximately 85% of individuals with FA by early adulthood and are a major cause of morbidity and mortality. The most common cardiac manifestations are heart failure and arrhythmias. Symptoms can include chest pain, shortness of breath, and heart palpitations. Cardiac problems can be treated with medication, though severe forms of heart disease can be fatal. Regular consultation with a cardiologist is essential for the management of cardiac complications. Diabetes mellitus is a condition characterized by abnormally high blood and urinary sugar levels, and affects about 10% of all individuals with FA, with a higher likelihood in those whose ataxia began before 10 years of age. Early symptoms of diabetes include increased thirst, increased urination, and unexplained weight loss. This can be managed with diet and medication. Cause of Friedreich Ataxia Friedreich Ataxia is caused by a genetic defect called “triplet repeat expansion.” Humans have 46 chromosomes, each made up of hundreds to thousands of genes. The chromosomes are organised into 23 pairs, with half inherited from the mother (chromosomes 1-22 and X) and half inherited from the father (chromosomes 1-22 and Y). Each chromosome is a tightly coiled chain of DNA which is made up of four different chemicals, or bases, usually represented by the letters A, T, C, and G. In a normal piece of DNA, you might see patterns where a certain set of three bases, or a “triplet”, repeats a few times. This is perfectly normal and healthy. However, in a triplet repeat expansion disorder, that pattern repeats too many times. This can cause problems because it changes the way the DNA works. In Friedreich Ataxia, there is a defect in a gene on chromosome 9 resulting from a triplet repeat expansion of a sequence of bases with the code GAA. The normal number of GAA repeats in this region is 7-34. However, in most individuals affected with FA, the GAA sequence is repeated between 600 and 1200 times. A greater number of repetitions is related to earlier onset and faster progression of the disorder. The triplet repeat expansion makes the gene unstable and reduces its ability to produce a protein called Autosomal Recessive Inheritance Pattern