Human Genetics at MEDIZINICUM

A special form of non-insulin-dependent diabetes mellitus type 2 is the "Maturity Onset Diabetes of the Young" (MODY). MODY is a hereditary form of diabetes mellitus and is caused by mutations in at least 11 genes. According to clinical studies, about 1 to 2% of patients with diabetes mellitus suffer from a form of MODY diabetes. According to the literature, a large number of MODY patients are misdiagnosed as type 1 or type 2 diabetes mellitus and are not adequately treated. In addition to early manifestation, the disease is characterized by a lack of diabetic autoantibodies, a creeping onset, which is initially usually noticeable through a comparatively mild increase in blood sugar, and a disorder of the pancreas. The differential diagnostic differentiation by means of a genetic test is of great importance, since in many cases not only the prognosis and therapy of MODY differ from those of type 1 or type 2 diabetes, but also the individual MODY forms differ in the extent of the increase in blood sugar and require special therapy strategies.

This type of metabolic disease affects about 60% of adults in Germany and may have genetic causes in addition to dietary deficiencies.

In disorders of fat metabolism, risk factors for vascular diseases, heart attacks and strokes play a major role. Hereditary disorders of the cholesterol metabolism are present in 1 in 300 people. Often the diagnosis is only made when an acute event such as a heart attack or stroke has occurred. Up to 10% of all people with coronary heart disease diagnosed before the age of 50 have a genetic alteration of the LDL receptor gene. Here, too, early knowledge can make it possible to initiate prophylactic measures to prevent secondary diseases.

The hereditary iron storage disorder is a common disease of the iron metabolism in which increased iron uptake in the small intestine leads to iron accumulation in various organs (especially the liver, pancreas, joints, heart, spleen, pituitary gland, thyroid gland and skin) with long-term tissue damage. Patients absorb about four times more iron via the intestine than healthy people and the total body iron content can therefore increase from approx. 2-6g (normal value) to up to 80g over several decades if untreated. The excess iron can lead to serious illnesses.

In addition to bloodletting therapy, there is also medicinal therapy with iron chelators.

Amyloidosis is the accumulation of abnormally altered proteins in the intercellular space. These deposits (amyloid fibrils) occur due to a disturbance in the folding of a normally soluble protein. Clinically, there are sensory disorders and polyneuropathies, which are mainly in the form of pain and weakness in the lower limbs and in the form of heart muscle weakness (cardiomyopathy), digestive disorders, incontinence, severe weight loss, sudden drop in blood pressure and dizziness. Patients usually fall ill between the ages of 30 and 70. Since 2011 there has been a drug treatment, which slows down the progression.

Alpha 1-antitrypsin (AAT) deficiency is a disease in which tissue destruction occurs as part of inflammation, particularly in the lungs and liver. The value is variable. If this is intensified by noxae, liver cirrhosis and pulmonary emphysema may occur. Chronic obstructive pulmonary disease (COPD) and pulmonary emphysema are the most common defects caused by AAT deficiency and usually do not occur until adulthood. Cigar smoke increases the risk of disease.

Hereditary angioedema (HAE) is an autosomal dominant hereditary disease with a tendency to the formation of recurrent, extensive swelling of the skin or mucous membranes, which most frequently manifests itself in the second decade of life, and not infrequently in the first. The cause is a deficiency of the C1-esterase inhibitor (C1-INH). Factors that can cause edema include primarily trauma such as injections, surgeries, dental surgery, injuries and minimal trauma. Anxiety, psychological stress situations and local infections, but also stronger and longer mechanical stress on the extremities, menstruation or taking hormonal contraceptives can also lead to swelling of the skin or mucous membranes.

CADASIL (acronym; "Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy") is a hereditary neurodegenerative disease that can lead to vascular dementia and familial stroke in middle age. In the early phase of the disease, CADASIL usually manifests itself with migraine-like headaches starting around the age of 30 and temporary circulatory disturbances and repeated strokes starting in middle adulthood.

Hereditary fructose intolerance results in vomiting and repeated drops in blood sugar levels as soon as fructose (fructose) or sucrose is added to the diet, as well as pronounced malnutrition.

Wilson's disease is caused by a hereditary defect in the copper-binding region of an enzyme in the liver and kidneys, which leads to a copper transport disorder and toxic copper storage in the liver, kidneys, eyes and brain. The therapy consists of a permanent treatment with certain drugs and in severe cases a liver transplant.