The symptoms of TPI deficiency vary from case to case. The disorder is characterized by hemolytic anemia and progressive neurological findings. Hemolytic anemia occurs before birth (neonatally) in approximately half of the cases.
Hemolytic anemia is a condition characterized by low levels of circulating red blood cells (erythrocytes) that occurs because red blood cells are prematurely destroyed and the bone marrow cannot compensate for the loss. Hemolytic anemia may cause fatigue, lightheadedness, yellowing of the skin and whites of the eyes (jaundice), pale skin color, and difficulty breathing.
Additional symptoms associated with TPI deficiency include increased susceptibility to infections, an abnormally enlarged spleen (splenomegaly), breathing difficulties due to paralysis of the muscle that separates the stomach and the chest cavity (diaphragm), and disease of the heart muscle (cardiomyopathy).
In most cases, life-threatening complications such as respiratory or heart (cardiac) failure occur during childhood. However, adults with TPI deficiency with less severe symptoms have been reported.
Progressive neurological symptoms are seen in infants with TPI deficiency usually between 6 and 30 months of age. Such symptoms include diminished muscle tone (hypotonia), weakness, muscular wasting or degeneration (amyotrophy), lack of deep tendon reflexes, and involuntary muscle spasms (spasticity) that result in slow, stiff movements of the legs.
Some individuals do not develop any additional neurological symptoms and intelligence is unaffected. In other cases, intellectual disability occurs along with tremors and dystonia. Dystonia is the name for a group of movement disorders that is generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures).
TPI deficiency is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.
Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Investigators have determined that TPI deficiency occurs due to disruption or changes (mutations) of a gene located on the short arm of chromosome 12 (12p13). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
TPI deficiency affects males and females in equal numbers. Approximately 30 to 50 cases have been reported in the medical literature since the disorder initial description in 1965.
A diagnosis of TPI deficiency is suspected based upon a thorough clinical evaluation, a detailed patient history, and identification of characteristic findings. A diagnosis may be confirmed by molecular genetic testing that identifies the characteristic genetic mutation associated with TPI deficiency.
Prenatal diagnosis is possible by measuring TPI enzyme activity in amniotic fluid cells and fetal blood cells. A procedure known as chorionic villus sampling (CVS) has also been used for prenatal diagnosis. This procedure involves the removal and study of tissue samples from the placenta.
No specific therapy exists for of TPI deficiency. Treatment is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, cardiologists, neurologists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.
Specific therapies may include blood transfusions to treat hemolytic anemia during episodes of red blood cell destruction (hemolysis) and assisted ventilation to treat paralysis of the diaphragm. Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
Research is underway to study various treatment options for individuals with TPI deficiency. Such treatment options include enzyme replacement therapy and bone marrow transplantation.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
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For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
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