What enzyme is responsible for converting galactose to its phosphorylated form, given a suspected deficiency in a 12-month-old girl with difficulty feeding, cataracts, and elevated galactose levels, specifically in the metabolic pathway where galactose is converted to galactose-1-phosphate by the enzyme galactokinase (GK)?

From the Guidelines

Galactokinase is the enzyme responsible for converting galactose to its phosphorylated form, galactose-1-phosphate. In this case, the 12-month-old girl is presenting with symptoms consistent with galactosemia, a metabolic disorder characterized by the inability to properly metabolize galactose. The clinical presentation of difficulty feeding, cataracts, and elevated blood galactose levels strongly suggests galactokinase deficiency, as stated in the study by 1. This enzyme catalyzes the first step in galactose metabolism, phosphorylating galactose using ATP as a phosphate donor. When galactokinase is deficient, galactose accumulates in the blood and tissues, leading to formation of galactitol in the lens of the eye, which causes cataracts. Unlike more severe forms of galactosemia (such as those caused by galactose-1-P uridylyltransferase deficiency), galactokinase deficiency typically presents with cataracts as the primary manifestation without liver or neurological involvement, as noted in the study by 1. Some key points to consider in the diagnosis and management of galactosemia include:

• The importance of early diagnosis and treatment to prevent long-term complications, as discussed in the study by 1.
• The use of newborn screening programs to identify affected individuals, as described in the study by 1.
• The need for dietary restriction of galactose-containing foods, particularly lactose-containing dairy products, as mentioned in the study by 1.
• The potential for variability in clinical presentation and severity of symptoms, as noted in the study by 1. Treatment involves eliminating galactose from the diet, primarily by restricting lactose-containing dairy products. It is essential to follow the guidelines and recommendations outlined in the studies by 1, 1, and 1 to ensure proper diagnosis and management of galactosemia. By prioritizing the most recent and highest-quality studies, we can provide the best possible care for patients with galactosemia, as emphasized in the studies by 1 and 1.

From the Research

Enzyme Deficiency in Galactose Metabolism

The pediatrician suspects an enzyme deficiency in the metabolic pathway of galactose where galactose is converted to its phosphorylated form. The enzyme responsible for this conversion is:

• Galactokinase

Evidence from Studies

Studies have shown that galactokinase (GALK) is the enzyme that converts α-d-galactose into galactose-1-phosphate (Gal-1-P) 2, 3, 4, 5. This enzyme is the first step in the Leloir pathway, which is essential for galactose metabolism. Deficiency in GALK has been associated with galactosemia type 2, an autosomal recessive disorder characterized by hypergalactosemia and formation of cataracts 5.

Role of Galactokinase in Galactosemia

Galactokinase plays a crucial role in the development of galactosemia, as it is responsible for the production of galactose-1-phosphate (Gal-1-P) 6. Elevated levels of Gal-1-P have been linked to the pathology of classic galactosemia, and studies have shown that GALK1 is necessary for the elevated Gal-1-P levels in this disease 6.

Conclusion Not Provided as per Request

As per the request, no conclusion will be provided. However, the evidence from the studies suggests that galactokinase is the enzyme responsible for converting galactose to its phosphorylated form, and its deficiency is associated with galactosemia type 2.