Galactokinase deficiency Health Article

Signs and symptoms

Galactokinase deficiency is associated with galactosemia and cataracts (clouding of the lens of the eyes resulting in blurred vision), but without the systemic manifestations of liver disease and severe mental retardation that are commonly found in classic galactosemia. The cause of the cataract is an accumulation of galactitol (sugar alcohol derivative of galactose) within the lens of the eye. This galactitol accumulation attracts water, resulting in swelling and damage of the lens fiber.

There are infrequent reports of mild mental retardation in people with galactokinase deficiency, but the over-whelming majority of people have been shown to have normal intelligence. The rare finding of pseudotumor cerebri (a syndrome of raised pressure within the skull) has also been reported. Several investigators have reported premature development of cataracts (between the ages of 20 and 40 years old), even in individuals who are heterozygous for the galactokinase deficiency mutation.

Diagnosis

Newborn screening is the act of testing all infants for a specific disease shortly after birth for the purpose of preventing disease progression through prompt medical treatment. When newborn screening for the inherited disease phenylketonuria (PKU), began in 1962, it quickly became clear that many infants with PKU were being identified for early treatment and that the mental retardation caused by the disease was being prevented.

This success encouraged R. Guthrie and others to consider additional metabolic disorders that might benefit from newborn screening. Since restricting dietary galactose early in life would prevent the development of irreversible symptoms, galactosemia appeared to be an ideal candidate for newborn screening. In 1963, Guthrie and his colleague, K. Paigen, developed a method to detect galactosemia that could be applied to the newborn blood specimen, and screening for galactosemia in the newborn became practical.

When trying to establish a diagnosis of galactokinase deficiency, an initial test is performed to detect galactosuria, or high levels of galactose in the urine that is seen with galactosemia. If that test proves positive, the next step is to determine which of the three enzymes needed to convert galactose to glucose is defective. When looking for galactokinase deficiency, blood samples are taken, and galactokinase activity is measured from red blood cells. If galactokinase activity is low, then the person has galactokinase deficiency. Thus, the diagnosis is made by demonstrating the deficiency of galactokinase in red blood cells and can be further confirmed by showing normal levels of the other two enzymes involved in this pathway using other tests. The disease can also be diagnosed before birth by testing fluid surrounding the unborn fetus for high levels of galactose, but this is rarely done.

Before widespread institution of newborn screening, these diagnostic tests were performed in infants with symptoms consistent with any form of galactosemia. As of the year 2000, newborn screening is mandated by law in every U.S. state except Louisiana, Pennsylvania, and Washington state.

Treatment and management

The galactosemia syndromes are effectively treated by rigid dietary exclusion of all lactose and galactose, primarily involving the elimination of milk and its products. A galactose-free diet should be initiated as early as possible, particularly because cataract formation may be reversed in early stages. Non-lactose milk substitutes are often used. Although soybean preparations contain bound galactose, they appear to be well-tolerated because the bound galactose is not readily absorbed by the intestine.

This galactose-free diet must be followed for life and requires close supervision, normally overseen by a team of health care professionals including a primary care provider, specialist physician, and a nutritionist. Periodic blood or urine measurements of galactose can be performed to monitor compliance with the restricted diet. Even with early diagnosis and strict dietary restrictions, people with galactosemia are at increased risk for cataract development in adulthood and should have regular eye examinations.

One detrimental effect of eliminating milk and milk products from the diet is the loss of adequate intake of vital nutrients such as protein, calcium, phosphorus, and riboflavin. As a result, nutritional deficiencies may develop, resulting in poor growth. Great care must be taken to achieve adequate daily supplementation with these nutrients after an infant is weaned from the enriched non-dairy formula. However, studies have demonstrated that children, adolescents, and adults often fail to routinely take prescribed supplements.

It also should be noted that exclusion of milk and milk products alone does not constitute a galactose-restricted diet, as galactose is found in other foods as well. Some fruits and vegetables with higher galactose content must also be avoided. Education of parents and children regarding galactose content of specific foods is important, and lists of foods can be obtained from nutritionists that prove useful in management.