NORD gratefully acknowledges Jan O. Aasly, MD, PhD, Consultant Neurologist/Professor of Neurology, Department of Neurology, St. Olav's Hospital, for assistance in the preparation of this report.
Phosphoglycerate kinase deficiency is an extremely rare inherited metabolic disorder characterized by deficiency of the enzyme phosphoglycerate kinase. This enzyme is essential for the breakdown of glycogen, resulting in the release of energy. Symptoms and findings associated with the disorder may include low levels of circulating red blood cells (hemolytic anemia); varying degrees of intellectual disability; rapidly changing emotions (emotional liability); an impaired ability to communicate through and/or to comprehend speech or writing (aphasia); exercise-induced pain, stiffness, or cramps; enlargement of the spleen (splenomegaly); and/or paralysis of one side of the body (hemiplegia). In most cases, phosphoglycerate kinase deficiency is inherited as an X-linked genetic trait. In such cases, the disorder is fully expressed in males only; however, some females who carry one copy of the disease gene (heterozygotes) may have hemolytic anemia.
The three main features of phosphoglycerate kinase deficiency are hemolytic anemia, intellectual disability, and muscle problems (myopathy). An individual with the disorder may be affected by one or more of these features, but it is unusual for one person to exhibit all three signs.
Individuals with childhood PGK deficiency have some degree of intellectual disability with delayed language acquisition. Some have epilepsy and strokes.
Most adult patients are moderately affected, and heterozygous females may show only mild hemolytic anemia with no myopathy or intellectual disability.
Myopathy with exercise-induced stiffness, cramps, and muscle pain is seen in adolescents and young adult males. The cramps are often severe and may incapacitate the individual for hours. Myoglobinuria is often seen in severe episodes.
PGK is considered to be an inborn error of metabolism that is inherited in an X-linked manner. The gene responsible is located on the X chromosome (Xq13).
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. 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 Xq13” refers to band 13 on the long arm of the X chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and manifest mostly in males. Females that have a defective gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and only one carries the defective gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a defective gene he will develop the disease.
Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.
If a male with an X-linked disorder is able to reproduce, he will pass the defective gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.
Phosphoglycerate kinase deficiency is a very rare disorder that is fully expressed in males only. However, females who carry a single copy of the disease gene (heterozygous carriers) may exhibit some symptoms associated with the disorder (i.e., hemolytic anemia). The disorder can be diagnosed at birth when enzymatic testing is done. More than 30 cases of PGK deficiency have been written up in the medical literature. It is thought that there are people with the disease who do not receive a diagnosis.
The diagnosis is made on the basis of a thorough physical examination and confirmed by the results of laboratory tests.
Treatment of phosphoglycerate kinase deficiency may consist of iron supplements and blood transfusions when needed. The avoidance of strenuous exercise when evidence that muscle breakdown has taken place is very important and special care is needed during neurologic crisis to avoid life-threatening situations. Bone marrow transplantation may be an option in cases with severe neurological deterioration.
Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.
Research on inborn errors of metabolism is ongoing. Scientists are studying the causes of these disorders and trying to design enzyme replacement therapies that will return a missing enzyme to the body.
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 TTY: (866) 411-1010 Email: [email protected]
For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
Contact for additional information about phosphoglycerate kinase deficiency:
Jan O. Aasly, MD, PhD
Consultant Neurologist/Professor of Neurology Dept of Neurology
St. Olav’s Hospital
7006 Trondheim, Norway Tel: +47 7257 5071 Mobile ph.: +47 951 96796
E-mail: [email protected]
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