Galactokinase Deficiency · What Is It, Causes, and More

Galactokinase deficiency is a rare metabolic disorder caused by a lack of galactokinase, an enzyme that helps break down galactose. Galactose is a simple sugar primarily found in lactose-containing foods like milk, cheese, and yogurt. Galactokinase facilitates the first step in galactose metabolism by converting  galactose to galactose-1-phosphate, allowing its use for energy production. In the absence of galactokinase, galactose accumulates in the body and may be converted to galactitol, a reduced form of galactose made when there is no other way to remove galactose from the body.  

Galactokinase deficiency is a type of galactosemia, a group of inherited disorders that cause increased levels of galactose in the blood. The most common form of galactosemia is type I or classic galactosemia, a deficiency of galactose-1-phosphate uridyltransferase (GALT) that can cause severe complications, including liver failure and neonatal death. 

Symptoms of galactokinase deficiency may begin as soon as an infant begins breastfeeding due to the lactose present in breastmilk. Infants commonly develop cataracts in both eyes in the first few weeks of life. Cataracts are characterized by clouding of the lens, the clear structure located at the front of the eye. With galactokinase deficiency, there is an accumulation of galactitol in the lens of the eye. This buildup can increase the pressure within the eye, which can cause swelling of the lens and, ultimately, cataracts.  

Signs that an infant has cataracts include difficulty following objects with their eyes and not smiling in response when someone smiles at them, as well as leukocoria, where the pupil may look cloudy or have a whitish reflex instead of the normal red reflex in photos. 

A child with galactokinase deficiency may also develop pseudotumor cerebri, which is characterized by pressure around the brain that mimics symptoms of a large brain tumor (e.g., changes to vision, nausea, ringing in the ears) without any actual brain lesions. The increased pressure typically results from galactitol buildup in the cerebrospinal fluid (CSF) surrounding the brain and spinal cord. Less common symptoms may also include poor feeding in infancy or failure to thrive, irritability or lethargy, and more rarely, vomiting.  

Unlike classic galactosemia, galactokinase deficiency usually does not cause liver damage, intellectual disability, or life-threatening complications, especially when diagnosed early and managed with a galactose-restricted diet. 

Galactokinase deficiency is treated with a lifelong lactose- and galactose-restricted diet, which requires limiting foods such as milk and all dairy products (e.g., cheese, yogurt, butter, cream). Lactose may also be found in many processed and prepared foods, such as baked goods, breakfast cereals, instant potatoes and soups, as well as salad dressings, so it’s important to check nutritional labels. Breastmilk also contains lactose, so infants need to be fed with a lactose-free formula (e.g., soy-based or elemental formulas). Because most of the calcium from the diet is found in dairy products, individuals may be prescribed calcium and vitamin D supplements to promote bone mineralization. 

Typically, cataracts that are due to galactokinase deficiency resolve after these dietary changes. In some cases, however, surgical removal of the cataracts may be necessary, especially if detected late or if visual development is affected. The individual or their guardians may be recommended to consult a nutritionist for help navigating the galactose-restricted diet. Parents may also be advised to consult a genetic counselor to discuss the likelihood of other family members inheriting the disease.