Galactitol is a sugar alcohol, also known as dulcitol, that forms as a byproduct of galactose metabolism in the body. It has a slightly sweet taste and is chemically related to galactose, a simple sugar found in dairy products and other foods. Galactitol’s presence in the body becomes significant when the normal pathways for galactose processing are disrupted, leading to its accumulation.
How Galactitol Forms and Where It Accumulates
Galactitol is produced from galactose through a reaction catalyzed by the enzyme aldose reductase. This process becomes problematic when there is a deficiency in enzymes involved in the primary metabolism of galactose, such as galactokinase. A deficiency in galactokinase is associated with Type II galactosemia, a rare inherited metabolic disorder. In this condition, galactose cannot be properly converted into galactose-1-phosphate, shunting it instead to the aldose reductase pathway, which produces galactitol.
Galactitol does not easily cross cell membranes, causing it to accumulate within various tissues. It is particularly prone to building up in the lens of the eye, where aldose reductase is highly concentrated. This accumulation also occurs in other areas of the body, including the brain, kidneys, and ovaries. Its accumulation in these specific areas is due to its osmotic properties, meaning it draws water into the cells, leading to swelling and potential cellular dysfunction.
Health Effects of Galactitol Buildup
The accumulation of galactitol in the body can lead to several health problems, with the most recognized being the development of cataracts. In the eye’s lens, galactitol’s osmotic activity causes water to rush into the lens fibers, resulting in swelling, membrane rupture, and protein denaturation, leading to cataract formation. These cataracts are often bilateral and can manifest in infancy or early adulthood in individuals with galactokinase deficiency.
Beyond cataracts, galactitol accumulation may contribute to other issues. In the brain, its osmotic nature can lead to cell swelling and brain edema. Some clinical reports have suggested mental impairment. Additionally, galactitol has been implicated in ovarian dysfunction, particularly premature ovarian insufficiency in females, by inducing osmotic stress and cell dysfunction. The accumulation can also deplete cellular glutathione, increasing susceptibility to oxidative stress in various tissues, including the ovaries and potentially nerves.
Addressing Galactitol-Related Conditions
Diagnosis of galactitol-related conditions, primarily galactosemia, often begins with newborn screening programs. These screenings measure the levels of total galactose and the activity of key enzymes, such as galactose-1-phosphate uridylyltransferase (GALT) or galactokinase, in blood spot samples. If an abnormal screening result is found, further confirmatory tests like enzyme assays and genetic testing are performed to pinpoint the exact enzyme deficiency.
The main management strategy for conditions involving galactitol buildup is strict dietary restriction of galactose. This means avoiding all milk products and other lactose-containing foods, replaced with lactose-free formulas for infants. Early diagnosis and prompt initiation of a galactose-restricted diet are important to prevent severe acute complications, such as liver failure, sepsis, and neonatal death. While early intervention can prevent many acute symptoms and cataracts, some individuals may still experience long-term complications, including developmental delays, speech problems, and, in females, ovarian dysfunction, despite consistent dietary management.