Deoxyguanosine kinase deficiency

Deoxyguanosine kinase deficiency is an inherited disorder that can disrupt the normal function of the liver, brain, and muscles. Researchers have described different forms of this disorder. Approximately 75 percent of affected individuals have the hepatocerebral form, which causes serious problems in the liver (hepato-) and brain (cerebral). Approximately 20 percent of people with deoxyguanosine kinase deficiency have the isolated hepatic form, which causes liver disease without serious neurological problems. The myopathic form is the least common form; it affects approximately 5 percent of people with deoxyguanosine kinase deficiency. The myopathic form causes problems with the skeletal muscles, which are the muscles used for movement. The signs and symptoms of deoxyguanosine kinase deficiency can vary, even among members of the same family. 

Infants with the hepatocerebral form of deoxyguanosine kinase deficiency typically have low blood glucose levels (hypoglycemia) and a buildup of lactic acid in the body (lactic acidosis) soon after birth. Within the first few weeks of life, these infants typically begin to show signs of liver disease and brain dysfunction. Neurological signs and symptoms may include weak muscle tone (hypotonia), abnormal involuntary eye movements (nystagmus), developmental delays, and, rarely, seizures. Early signs of liver disease may include an enlarged liver (hepatomegaly) and yellowing of the skin and the whites of the eyes (jaundice). Liver disease usually progresses to liver failure. 

Signs and symptoms of the isolated hepatic form of deoxyguanosine kinase deficiency may appear soon after birth or during childhood. Like those with the hepatocerebral form, people with the hepatic form often have liver disease that worsens over time and may progress to liver failure. Some affected individuals have additional signs and symptoms that indicate the involvement of other body systems, such as the kidneys and the heart. 

Signs and symptoms of the myopathic form often appear in adulthood, although they sometimes appear earlier in life. In addition to problems with the skeletal muscles, people with the myopathic form of deoxyguanosine kinase deficiency can have heart problems, brain abnormalities, or weakness of the eye muscles. People with the myopathic form typically do not have liver disease. 

Without intervention, most individuals with deoxyguanosine kinase deficiency have a shortened life expectancy. Those with liver disease typically do not survive past early childhood, while those with the myopathic form may survive into middle or late adulthood.