PEPCK deficiency is an extremely rare disorder of carbohydrate metabolism inherited as an autosomal recessive trait. A deficiency of the enzyme phosphoenolpyruvate carboxykinase (PEPCK), which is a key enzyme in the conversion of proteins and fat to glucose (gluconeogenesis), causes an excess of acid in the circulating blood (acidemia). Characteristics of this disorder are low blood sugar (hypoglycemia), loss of muscle tone, liver enlargement and impairment, and failure to gain weight and grow normally.
There are two forms of PEPCK deficiency: cytosolic and mitochondrial. Both forms represent an inherited deficiency in the enzyme phosphoenolpyruvate carboxykinase. This enzyme is key in the process of converting proteins and fat to glucose (gluconeogenesis).
Symptoms of this disorder include the presence of excess acid in the circulating blood (lactic acidemia); loss of muscle tone (hypotonia); abnormal enlargement of the liver (hepatomegaly); inability to gain appropriate weight and grow normally (failure to thrive); and an abnormally low blood sugar (glucose) level (hypoglycemia). Glucose is essential as the body’s source of energy, and for the functioning of many organs and systems in the body, especially the central nervous system.
At or shortly after birth, the infant with PEPCK deficiency may have an enlarged liver, apnea, and a moderate delay in motor functions. Poor appetite, vomiting, coma, convulsions, and seizures may be present. Liver impairment produces increased liver enzymes, alanine, glycine, and glutamine levels. At least one case reported to date has involved atrophy of the optic nerve.
The course of this disorder can be very rapid.
PEPCK deficiencies, in both forms, are very rare disorders that are inherited as autosomal recessive traits. The abnormal gene that is responsible for the cytosolic (soluble) form of PEPCK deficiency has been traced to gene map locus 20q13.31.
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 20q13.31″ refers to band 13.31 on the long arm of chromosome 20. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait 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, therefore, 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 a few 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.
PEPCK deficiency is extremely rare. One overview suggests that only 10 cases have been reported in the medical literature.
Diagnosis of PEPCK deficiency can be made shortly after birth by biochemical analysis of fibroblast cells.
Genetic counseling may be of benefit for patients and their families. Other treatment is symptomatic and supportive.
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FROM THE INTERNET
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