Rare genetic disease

    Last updated date: 23-May-2023

    Originally Written in English

    Rare Genetic Disease

    Rare Genetic Disease

    Knowledge of genetics is useful in family medicine for assessing a patient's risk for a genetic disease and counseling patients about potential dangers connected with subsequent childbearing. In today's world, a family physician plays a variety of roles in dealing with genetic problems. Because of the expansion in genetics knowledge, all primary care physicians must be knowledgeable of the practical advances in this field.


    Genetic Disease

    Genetic Disease

    A genetic disorder is a condition caused in part or entirely by a deviation from the usual DNA sequence. A single gene mutation (monogenic disorder), multiple gene mutations (multifactorial inheritance disorder), a combination of gene mutations and environmental factors, or chromosome damage (alterations in the number or structure of chromosomes) can all produce genetic disorders.

    Scientists are learning that practically all disorders have a genetic basis as they uncover the secrets of the human genome (the whole set of human genes). Some disorders, such as sickle cell disease, are caused by mutations that are inherited from one's parents and present at childbirth. Other diseases are caused by mutations in a gene or a collection of genes that occur over the course of a person's life. These mutations are not inherited from a parent, but rather occur at random or as a result of exposure to environmental factors (such as cigarette smoke). Many malignancies, as well as some types of neurofibromatosis, fall within this category.



    Amyloidosis is a condition in which amyloid proteins accumulate in essential organs. These organs swell and lose function as a result of protein accumulation.

    Our bodies produce several proteins that can lead to amyloidosis. To treat a patient with amyloidosis, it's essential to identify the particular protein that's causing the problem.


    What is AA Amyloidosis?


    When the body is inflamed (irritated and swollen), serum amyloid A protein is produced in significant quantities. When Serum Protein A concentrations in the bloodstream stay high for an extended length of time, AA amyloidosis develops. Rheumatoid arthritis, inflammatory bowel disease, and chronic infections are examples of chronic inflammatory disorders that can be seen in amyloidosis AA. Inherited periodic fever syndromes, such as Familial Mediterranean Fever, are also involved. Because of the underlying inflammatory condition, AA amyloidosis is also known as secondary amyloidosis. It is more prevalent in underdeveloped countries. The heart is rarely affected by this form.


    Amyloidosis Causes

    Amyloidosis is a misfolding condition of proteins.  When proteins in the bloodstream have completed their function, they are normally eliminated and/or recycled. However, in amyloidosis, a protein might alter structure (or misfold) and become unable to be removed. Misfolded proteins cluster together to produce amyloid fibrils, which are then accumulated between the cells of important organs. The cells in one or more tissues and organs can no longer work together when amyloid fibrils accumulate, and the organ loses function.


    Amyloidosis Symptoms

    Amyloidosis Symptoms

    Many organs can be affected by AA amyloidosis, which causes the following indications and symptoms:

    • The signs and symptoms that your kidneys are in distress include leg and feet swelling, pee with a lot of bubbles (foamy/frothy urine), and less urination
    • The symptoms that indicate a problem with the liver include liver enlargement (hepatomegaly)
    • Symptoms that indicate a problem with the gastrointestinal system include hemorrhage, constipation, and diarrhea
    • Symptoms that indicate a problem with the heart (uncommon) include feet and leg swelling, breathing problems, irregular heartbeats, and pain in the chest
    • Other symptoms and signs include spleen enlargement (splenomegaly), risen urine protein levels (proteinuria), and cholesterol levels are high (hypercholesterolemia)


    Amyloidosis Diagnosis

    Patients with persistent inflammatory or rheumatic disease who develop signs and symptoms of AA amyloidosis are investigated. In AA amyloidosis, the kidney is the most commonly affected organ.

    To diagnose AA amyloidosis, a biopsy (the removal of cells or tissue) is needed. A fat pad biopsy, or a biopsy of abdominal fat immediately beneath the skin, is frequently the first place biopsied. If the fat pad biopsy is negative, the affected organ is usually biopsied next. A biopsy of the afflicted organ is sometimes the first step taken by the clinician.

    If the biopsy is positive, the tissue sample is tested again to rule out AL amyloidosis, which is a different kind of amyloidosis. The early indications and symptoms of AL amyloidosis are similar to those of AA amyloidosis; however, it is a more severe form of amyloidosis.


    Amyloidosis Treatment

    Amyloidosis Treatment

    To prevent additional amyloid deposition in AA amyloidosis, the underlying chronic inflammatory disease must be treated. Colchicine is quite effective. Anti-TNF, anti-IL-1, and anti-IL-6 biologic therapies can be utilized to lower the risk of active AA amyloidosis in people with autoimmune and rheumatic diseases. Other diseases like Crohn's disease, ulcerative colitis, and rheumatoid arthritis have a variety of therapeutic choices. The AA amyloidosis gradually regresses as the inflammation associated with these diseases is managed with treatment.

    Medications that target and remove the amyloid fibril basic components from the blood, as well as antibodies that attack and eliminate amyloid fibrils that have already been formed, are among the new therapeutics in the research and development phase.


    Adrenoleukodystrophy (ALD)

    Adrenoleukodystrophy (ALD)

    An uncommon genetic disorder known as adrenoleukodystrophy (ALD) creates an accumulation of very long-chain fatty acids (VLCFAs) in the brain. The protective myelin coating around nerve cells, which is responsible for brain function, is destroyed when VLCFAs aggregate. The nerves can no longer transport signals to and from the brain without the myelin coating.

    ALD is caused by a faulty gene, often known as a genetic mutation, which can result in various but related diseases, including adrenomyelopathy (AMN), Addison's disease, and the most prevalent and deadly variant (cerebral ALD). Cerebral ALD affects males between the ages of four and ten, resulting in irreversible disability and death in 4 to 8 years.

    ALD affects one out of every 20,000 males. Although not all females with the ALD gene mutation get the full ALD syndrome, about half of them may experience some symptoms.


    Adrenoleukodystrophy Causes

    A mutation in the ABCD1 gene on the X chromosome causes ALD, which is an X-linked recessive disorder. Because a female has two X chromosomes, she can inherit the defective gene and still have another X chromosome to compensate for the mutation. However, because males only have one X chromosome, the condition is caused by this gene defect.

    Female ALD carriers have a 24% probability of producing a carrier daughter and a 26% risk of having a boy with the disorder with each pregnancy.


    Adrenoleukodystrophy Symptoms

    Between the ages of 4 and 10, boys with cerebral adrenoleukodystrophy start to show symptoms. The following are the most frequent signs and symptoms:

    • Behavioral issues
    • Aggressiveness or withdrawal
    • A terrible memory
    • A low academic record
    • Reading and writing difficulties, as well as problems interpreting speech

    Other signs and symptoms of cerebral ALD that develop as the disorder worsens include:

    • Issues with vision
    • Convulsions
    • Swallowing problems
    • Hearing loss
    • A lack of coordination
    • inability to respond or communicate

    ALD advances quickly without management, often resulting in a vegetative state or death within a few years.


    Adrenoleukodystrophy Diagnosis

    Because there is a limited window in which cerebral ALD can be managed, it is crucial to get a diagnosis as soon as possible. There is no alternative to recover the destroyed myelin or reverse the neurological problems once the disease has progressed.


    Diagnostic Testing

    Rare genetic disease Diagnostic Testing

    Most women are unaware that they are carriers of ALD unless they have a family history of the disease. As a result, their kids' symptoms are frequently misunderstood and confused with behavioral or developmental problems.

    When a doctor suspects ALD, they will conduct two tests: an MRI scan to see if there is any damage to the brain tissue and a blood test to see if the concentration of very long-chain fatty acids, which are increased in males with ALD, is high.


    Genetic Testing

    ALD is caused by a faulty gene, which can be identified by genetic testing. It can also properly identify other family members with ALD, including female carriers and boys who haven't yet shown symptoms.


    Newborn Screening

    Newborn Screening

    A newborn screening test that detects high very long-chain fatty acid blood levels, a strong indication of ALD, was introduced to the United States Recommended Uniform Newborn Screening Panel in 2016 but is presently only available in some states. Boys at concern can be detected and treated early through neonatal screening.


    Adrenoleukodystrophy Treatment

    Stem Cell Transplant

    Stem Cell Transplant

    A stem cell transplant, in which the patient is receiving blood-forming stem cells from a genetically matched donor, is the only successful therapy option for cerebral ALD. The goal is to provide healthy stem cells that can produce the protein that is missing in ALD kids.

    There is a prolonged preparation phase that occurs before stem cell transplantation. Chemotherapy is utilized to prepare the body for the donor cells. Although it has been established that a donor stem cell transplant can slow the progression of ALD, it comes with its own unique challenges and risks:

    • Finding a donor match with a comparable or identical genetic composition might be challenging.
    • Because the immune system is suppressed to enable the recipient's body to receive the transplanted new stem cells, there is a high risk of infection.
    • The disease continues to worsen for 6-18 months after transplant, therefore early therapy is important.
    • A transplant can sometimes be associated with a rapidly progressing disease in symptomatic kids.


    Gene therapy for ALD

    The use of gene therapy as a therapy for cerebral ALD is being investigated. For asymptomatic ALD kids, a clinical study at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center adopts an experimental technique. Their own blood stem cells are extracted and treated in the lab using a vector, which is a non-infectious virus used to introduce the gene that produces the ALD protein (ABCD1 gene) into the cell. An intravenous infusion is used to restore the cells bearing the vector and the new gene to the patient. These new cells will carry the ABCD1 gene and will help to break down the very long-chain fatty acids that cause the significant neurological symptoms of ALD when they mature, divide, and generate new cells in the body.

    While still experimental, the advantage of this process is that there is no need to find a donor, which means there is no risk of the transplant attacking the body (a condition known as graft-versus-host disease), and thus no need for powerful immunosuppressive medications.


    Ehlers-Danlos Syndrome

    Ehlers-Danlos Syndrome

    Ehlers-Danlos syndrome is a group of diseases that damage the body's connective tissues. Cartilage, bone, fat, and blood are among these tissues. They provide support to organs and other tissues all around the body.

    Ehlers-Danlos syndrome is divided into 13 kinds depending on the most noticeable symptoms and the regions of the body where symptoms manifest. Symptoms of the most frequent form include very loose joints and delicate skin that tears easily.

    Ehlers-Danlos syndrome is a genetic condition that can be handed down through generations. The most prevalent type of Ehlers-Danlos syndrome affects about 1 in 5,000 to 20,000 persons.


    Ehlers-Danlos Syndrome Causes

    Ehlers-Danlos syndrome is caused by a deficiency in collagen (proteins that contribute to flexibility and strength of connective tissue). A defective gene causes people with the condition to have weaker collagen or not enough normal collagen in their tissues. The ability of connective tissue to support muscles, organs, and other tissues can be harmed by these deficiencies.


    Ehlers-Danlos Syndrome Symptoms

    Ehlers-Danlos Syndrome Symptoms

    The symptoms of Ehlers-Danlos syndrome vary depending on the kind. Ehlers-Danlos hypermobility, often known as hypermobile EDS, is the most frequent kind of disorder. Among the signs and symptoms are:

    • Hypermobile joints (hyperflexible)
    • Unsteady joints
    • Skin that is softer, thinner, and stretches more than usual
    • Extensive Bruises


    Ehlers-Danlos Syndrome Diagnosis

    Imaging studies

    Ehlers-Danlos syndrome is diagnosed using your family history and a variety of tests. It's possible that your diagnosis will include:

    • Physical examination. Doctors can examine how much the skin extends and how far the joints can move during a physical exam.
    • Imaging studies. Tests that produce images of the inside of the body can benefit doctors in detecting anomalies such as heart disease and twisted bones. X-rays are among the tests performed.
    • Genetic testing. Looking for a defective gene is the most typical technique to diagnose the disease.
    • A biopsy. It is a test that a doctor may conduct in specific instances. In this test, a sample of skin is removed and examined under a microscope for evidence of the disorder, including specific genetic mutations (abnormalities).


    Ehlers-Danlos Syndrome Treatment

    Ehlers-Danlos Syndrome Treatment

    The goal of Ehlers-Danlos syndrome treatment is to keep hazardous consequences at distance. It can also aid in the prevention of damage to the joints, skin, and other tissues. Treatment for an individual is determined by a variety of criteria, including the disorder's kind and manifestations.

    Doctors advise wearing sunblock and mild soaps to protect the skin. Vitamin C supplementation can help to minimize bruising. Joint injuries can be avoided through physiotherapy (exercises to improve the muscles that support the joints). Braces also aid in the stabilization of joints.

    Because blood vessels in children with Ehlers-Danlos syndrome are fragile, doctors will closely monitor them and may prescribe medication to keep blood pressure low and stabilized.

    People with Ehlers-Danlos syndrome are prone to dislocated joints and other joint problems. As a result, doctors advise them to avoid:

    • Heavy lifting.
    • High-impact exercise involves pounding the ground with the body.
    • Sports involving physical contact.


    Ehlers-Danlos Syndrome Complications

    Some kinds of Ehlers-Danlos syndrome have life-threatening complications. Blood vessels can burst in some kinds of Ehlers-Danlos syndrome, such as vascular Ehlers-Danlos syndrome. This can result in internal hemorrhage and stroke, both of which are serious.

    Organ rupture is also more common in people with certain kinds of Ehlers-Danlos syndrome. Most typically, the intestines or the uterus of a pregnant woman.

    Other types of Ehlers-Danlos syndrome have different problems depending on the type. The following are examples of complications:

    • Complications in the heart's valves
    • Severe spinal curvature
    • Corneal thinning in the eyes
    • Problems in the gums and teeth


    Mitochondrial Diseases

    Mitochondrial Diseases

    Mitochondrial disease, sometimes known as a mitochondrial disorder, is a collection of disorders affecting the mitochondria, which are small compartments found in practically every cell of the body. The primary purpose of the mitochondria is to generate energy. To produce more energy, more mitochondria are required, particularly in high-energy-demanding organs such as the heart, muscles, and brain. When the density or function of mitochondria in a cell is disrupted, the cell produces less energy, resulting in organ malfunction.

    Different symptoms may appear according to which cells in the body have mitochondrial dysfunction. Tired, exhaustion, metabolic strokes, seizures, cardiomyopathy, arrhythmias, developmental or cognitive problems, diabetes mellitus, deterioration of hearing, eyesight, growth, hepatic, gastrointestinal, or renal function are all symptoms of mitochondrial disease. These signs and symptoms can appear at any age, from childhood to late adulthood.


    Mitochondrial Diseases Causes

    Mitochondria are unique in having their own DNA, known as mitochondrial DNA (mtDNA). Mitochondrial disease can be caused by mutations in this mtDNA or nuclear DNA (DNA located in the nucleus of a cell). Toxins in the environment can also cause mitochondrial disorders.


    Mitochondrial Diseases Symptoms

    Mitochondrial Diseases Symptoms

    Symptoms of the mitochondrial disease include:

    • Slow growth
    • Muscle weakness and loss of coordination
    • Convulsions
    • Autism spectrum disorder (ASD)
    • Problems with vision and/or hearing
    • Learning difficulties and developmental delays
    • Diseases of the heart, liver, or kidneys
    • Constipation.
    • Diabetes mellitus
    • Diseases of the lungs
    • Higher infection risk.
    • Thyroid and/or adrenal problems
    • Autonomic nervous system dysfunction
    • Confusion, disorientation, and memory problems


    Mitochondrial Diseases Diagnosis

    Every 30 minutes, a child is born with a mitochondrial disease that will manifest by the age of ten. Mitochondrial disease affects about one out of every 4,400 people in the United States. Mitochondrial disease can be difficult to detect and is frequently misdiagnosed due to the various possible manifestations.

    There are several methods for determining whether or not someone has mitochondrial disease. Genetic diagnostic procedures, genetic or biochemical testing in problematic tissues such as muscle or liver, and other blood or urine-based biochemical parameters are examples of these. However, the understanding of mitochondrial disorders is continually developing, and we do not yet understand all of the genes that could lead to these diseases.


    Mitochondrial Diseases Treatment

    child nutrition

    There is presently no approved cure or treatment for mitochondrial disease. Supportive therapy, which may include nutritional management, exercises, and/or vitamins or amino acids supplements, is used to treat the mitochondrial disorder.

    Knowing the root of your or your child's problem will aid your health care team in determining the correct course of treatment. The team coordinates your treatment with your general care practitioner, neurologist, and other specialists.

    Based on your child's diagnosis, the experts will provide appropriate mitochondrial disease counseling, including an understanding of mitochondrial disease characteristics and genetics.

    The day-to-day medical concerns related to mitochondrial disease will be managed by your child's neurologist or primary care doctor.


    Is Alzheimer's a Genetic Disease?


    It is not required for someone to have a family history of Alzheimer's to develop the disease. Those who have a close family member with Alzheimer's disease, on the other hand, are more likely to develop the condition than those who do not have a first-degree relative with Alzheimer's. Those with more than one first-degree relative diagnosed with Alzheimer's disease are at an even greater risk. When diseases such as Alzheimer's and other dementias occur in families, it's possible that genetics (inheritable factors), environmental factors, or both play a significant role.


    Is Cancer Genetic Disease?


    Cancer is a genetic disease, meaning it is caused by alterations in genes that control how our cells behave, particularly how they proliferate and grow.

    Proteins play a major role in our cells, and genes provide the instructions for producing them. Certain gene mutations can cause cells to escape normal growth regulators and turn cancerous. Some cancer-causing gene alterations, for example, increase the synthesis of a protein that causes cells to proliferate. Others cause a misshapen and thus nonfunctional form of a protein that ordinarily repairs cellular damage to be produced.

    If the mutations are present in germ cells (the body's reproductive cells) we can inherit cancer-causing genetic abnormalities from our parents (eggs and sperm). Such mutations, referred to as germline mutations, are often identified in every cell of the offspring.

    During one's lifespan, cancer-causing genetic alterations can be acquired as a result of errors that occur while cells divide or from exposure to carcinogenic agents that cause DNA damage, such as some compounds in tobacco smoke, and radiation, such as UV rays from the sun. Somatic (or acquired) alterations are genetic changes that occur following conception.



    It's possible that the mother or father will pass down genetic defects to their child. When a gene becomes faulty as a result of a mutation or alteration, genetic disorders arise. A gene or a portion of a gene may be absent in some situations. These abnormalities occur during conception and are generally unavoidable. One or both parents may have a family history of a certain defect.