Galactokinase Deficiency

Galactokinase deficiency is a rare deficiency of galactokinase, an enzyme that helps break down galactose. Galactose is a simple sugar that is most often in foods containing lactose (e.g., milk, cheese, yogurt). When galactose is eaten, galactokinase speeds up the conversion of galactose to galactose-1-phosphate, which is the first step in producing energy from galactose. Galactose or galactitol, a reduced form of galactose made when there is no other way to remove galactose, may build up in the body if there is a deficiency of galactokinase. 

Infants and children with galactokinase deficiency commonly develop cataracts of both eyes. 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 of galactitol can increase the pressure of the eye, which can cause swelling 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. 

A child with galactokinase deficiency may also develop a 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). The increased pressure typically results from galactitol buildup in the cerebrospinal fluid (CSF) surrounding the brain and spinal cord.

Symptoms may begin as soon as an infant begins breastfeeding due to the lactose present in breastmilk. Additional, less common symptoms include lack of coordination, cognitive impairment, deafness, a small head, small gonads (i.e., testicles, ovaries), and slow growth in height and weight. 

Galactokinase deficiency is diagnosed by a medical evaluation, including assessment of the individual’s signs and symptoms and review of their medical history, followed by a thorough physical examination. Laboratory blood and urine tests can check for high levels of galactose in the individual’s blood and urine. Sometimes, a newborn screening will reveal an increase of galactose in the newborn’s blood, which may indicate a galactokinase deficiency. If initial tests indicate high galactose levels, additional blood tests may be recommended to investigate the levels of galactokinase in the blood and possibly assess for alterations to the sequence of the GALK1 gene.

Individuals who have cataracts typically need a detailed eye examination by a general clinician or ophthalmologist, a clinician who specializes in disorders of the eyes. Moreover, most individuals with pseudotumor cerebri will require imaging of the brain, such as computerized tomography (CT) scans or magnetic resonance imaging (MRI), to confirm diagnosis. A lumbar puncture, a procedure in which a clinician uses a hollow needle to remove CSF from the lower back and measure the pressure in the CSF, can also confirm a diagnosis of pseudotumor cerebri.

Galactokinase deficiency, a form of galactosemia, is a genetic condition that results in the buildup of galactose in the body. Galactokinase deficiency is usually caused by a mutation in the GALK1 gene. Cataracts or pseudotumor cerebri can be symptoms for an infant with galactokinase deficiency. The condition is often diagnosed through a medical evaluation and blood tests. Treatment usually consists of a lactose- and galactose-restricted diet with calcium supplementation.