There are thousands of metabolic disorders with symptoms that range from mild to devastating. They are difficult to diagnose because many of the symptoms mimic other diseases and often occur in combination. In general, metabolic disorders are inherited genetic defects that interfere with the body's metabolism, or the process by which the body gets energy from food. Symptoms vary from syndrome to syndrome, but often include developmental delays, vision and hearing problems, loss of intellectual function, muscle weakness, seizures, abnormal movements, stunted growth, pain and shortened life span. It is not unusual for the affected child to have been misdiagnosed with cerebral palsy, autism or other conditions whose symptoms can be similar to metabolic disorders. One in every 4,000 children are affected by one of these disorders.
In some cases, dietary changes and vitamin supplements may help alleviate symptoms, but there is currently no cure for metabolic disorders. A successful bone marrow or stem cell transplant may help slow or halt the progression of certain syndromes, but early diagnosis is critical to prevent irreversible disease progression.
An immune deficiency disease may be caused either by an inherited defect in the cells of the immune system or by an environmental agent. In the case of an inherited defect, the resulting disease is referred to as primary immune deficiency disease. According to the World Health Organization, there are more than 200 of these sometimes very rare inherited defects. Primary immune deficiency diseases affect many thousands of children and adults in the United States.
When the damage is caused by an environmental agent, the resulting disease is referred to as secondary immune deficiency disease. Secondary immune deficiencies can be caused by irradiation, chemotherapy, malnutrition and burns.
Immune deficiency is a state in which the immune system's ability to fight infection is compromised or entirely absent. The most apparent sign of an immune deficiency is frequent illness. Because a normal immune system protects the body against infection, patients with primary immune deficiencies are more susceptible to infections of all kinds. Those infections commonly involve skin, sinuses, throat, ears, lungs, brain, spinal cord, urinary tract and intestinal tract. The increased vulnerability to infection may result in repeated infections, infections that won't clear up or unusually severe infections. People with primary immune deficiencies often develop serious and debilitating illnesses. Fortunately, with proper medical care, many patients live full and independent lives.
A number of the more rare primary immune deficiencies are diagnosed in early childhood and result in shortened lives with extreme susceptibility to infection and malignancy:
CVID, Common Variable Immune Deficiency, is characterized by onset between 24 months of age and young adulthood with increased susceptibility to infection and diminished response to vaccines. Individuals may experience meningitis or other systemic bacterial infections, recurrent eye or skin infections and gastrointestinal symptoms including chronic diarrhea and bloating. They have increased susceptibility to malignancies, especially lymphomas, and may also develop breast cancer, prostate cancer and skin cancer.
SCID, Severe Combined Immunodeficiency, is characterized by one or more serious, life-threatening infections within the first few months of life. They may include pneumonia, meningitis or bloodstream infections. SCID, or “bubble boy disease,” became a household name during the 1970’s with the filming of David Vetter, a boy who lived for 12 years in a plastic, germ-free bubble.
According to Dr. Rebecca Buckley, Chief of Duke’s Division of Pediatric Allergy and Immunology, "Early diagnosis of SCID is rare because doctors do not routinely perform a test in newborns to count white blood cells. Such a blood test could pick up children with SCID as well as those with other serious immune deficiencies that would not be apparent until the child developed an infection. A simple blood test could allow us to treat, and most likely cure, SCID in an infant at a reasonable cost. If found later, less effective treatment can run into the millions." She goes on to say, "… essentially every baby with SCID could be cured if diagnosed early enough. SCID should be considered a pediatric emergency."
Enzymes are special types of proteins required to break down food molecules into fuel during metabolism, the process by which the body gets energy for normal growth and development. Enzyme deficiencies, or the absence of these enzymes, are inherited defects that result in a number of life-changing or life-threatening conditions:
MPS The mucopolysaccharidoses are a group of inherited diseases in which a defective or missing enzyme causes complex sugar molecules to accumulate in cells. As a result, progressive damage is done to the heart, bones, joints, respiratory system and central nervous system. While the disease may not be apparent at birth, signs and symptoms develop with age as more cells become damaged. It is estimated that one in every 25,000 babies born in the United States has some form of MPS.
LSD Lysosomal storage disorders are a group of approximately fifty inherited disorders that occur when a missing enzyme results in the body’s inability to recycle cellular waste. The severity of the disorder depends on the type and amount of cellular debris that accumulates, but almost all disorders are progressive. Many of these children die in infancy or early childhood. It is estimated that one in every 5,000 babies born in the United States has some form of an LSD. Affected individuals often have mental retardation, cloudy corneas, short stature, stiff joints, incontinence, speech and hearing impairment, chronic runny nose, hernia, heart disease, hyperactivity, depression, pain and a dramatically shortened life span.
NP Niemann-Pick disease refers to a group of inherited metabolic disorders known as lipid storage diseases in which the absence of a critical enzyme allows harmful quantities of fatty substances called lipids to accumulate in the spleen, liver, lungs, bone marrow and brain. Symptoms may include lack of muscle coordination, brain degeneration, learning problems, loss of muscle tone, increased sensitivity to touch, spasticity, feeding and swallowing difficulties, slurred speech and an enlarged liver and spleen. The most common type, Type A, occurs in infants. Children with this type rarely live beyond 18 months. Type B involves an enlarged liver and spleen, which usually occurs in the pre-teen years. The brain is not affected. Types C and D may appear early in life or develop later in the teens. These individuals may have only moderate enlargement of the spleen and liver, but brain damage may be extensive and cause an inability to look up and down, difficulty in walking and swallowing and progressive loss of vision and hearing. Type D usually occurs in people with an ancestral background in Nova Scotia.
The National Institute of Neurological Disorders and Stroke (NINDS), a part of the National Institutes of Health (NIH), conducts research on Niemann-Pick and a number of these other rare childhood diseases in laboratories at the NIH. They also support additional research through grants to major medical institutions across the country.
Leukodystrophy refers to a group of more than 15 rare genetic disorders that cause progressive degeneration of the white matter of the brain due to imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fiber. The leukodystrophies are often referred to as demyelinating diseases.
Myelin insulates nerve cells in the brain and spinal cord, helping them to transmit electrical nerve signals. Damage to this insulation slows down or blocks messages between the brain and the rest of the body. Without myelin, nerve cells cease to function and eventually die.
The most common symptom of a leukodystrophy is the gradual decline of an infant or child who previously appeared well. There is often a slowdown in mental and physical development. Symptoms vary according to the specific type of leukodystrophy, and may be difficult to recognize in the early stages of the disease.
Bone marrow transplantation has been shown to be successful in treating adrenoleukodystrophy, or ALD (ALD is the disease described in the book and 1992 Academy Award-nominated movie Lorenzo’s Oil), and is currently being researched as a treatment for others. ALD occurs in one in every 40,000 male births. The most common leukodystrophies include Canavan disease, Krabbe disease, metachromatic Leukodystrophy (MLD), Childhood Ataxia with Central Nervous System Hypomyelination (CACH), Alexander disease and Refsum disease.
How can these children be helped?
A successful bone marrow stem cell transplant may help children diagnosed with these rare childhood disorders.
The NFCTR is supporting an active clinical collaboration between internationally recognized research teams at the University of Louisville and Duke University to treat a number of rare or inherited childhood diseases. They are currently seeking FDA approval for a specific protocol to transplant small amounts of healthy bone marrow into children with metabolic disorders. The goal is for the transplanted healthy marrow to eliminate both the symptoms of disease and the need for future treatment. This “mini” bone marrow transplant does not require a perfect donor match and may be performed as an outpatient procedure.
See what Collaborators Have to Say
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Dr. Suzanne Ildstad |
Dr. Joanne Kurtzberg |
Dr. Suhag Parikh |
Professor of Surgery, University of Louisville |
Professor of Pediatrics and Pathology, Duke University |
Assistant Professor of Pediatrics, Duke University |
Director, Institute of Cellular Therapeutics |
Director, Pediatric Blood and Marrow Transplant Program |
Pediatric Blood and Marrow Transplant Program Hematologist/Oncologist |
Jewish Hospital Distinguished Professor of Transplantation |
Director, Carolinas Cord Blood Bank |
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Useful / Helpful links
National Organization for Rare Disorders (NORD)
http://www.rarediseases.org
NIH / Genetic and Rare Diseases Information Center (GARD)
http://www.rarediseases.info.nih.gov/GARD
National Institute of Child Health and Human Development (NIH)
http://www.nichd.nih.gov/publications/pubs/primary_immuno.cfm
Immune Deficiency Foundation (IDF)
http://primaryimmune.org
Primary Immunodeficiency Resource Center
http://www.info4pi.org
GeneReviews
http://www.ncbi.nim.nih.gov
Severe Combined Immunodeficiency
http://www.scid.net
ISMRD: The International Advocate for Glycoprotein Storage Diseases
http://www.mannosidosis.org/index.htm
National Institute of Neurological Disorders and Stroke
http://www.ninds.nih.gov/disorders/leukodystrophy/leukodystrophy.htm
United Leukodystrophy Foundation
http://www.ulf.org
National Tay-Sachs and Allied Diseases Association
http://www.ntsad.org
National Niemann-Pick Disease Foundation, Inc.
http://www.nnpdf.org
Hide and Seek Foundation for Lysosomal Storage Disease Research
http://www.hideandseek.org