What is Galactokinase Deficiency?
Info from http://www.galactosemia.org/understanding-galactosemia/#GKD
Galactokinase deficiency results from inheritance of deleterious mutations in the human GALK1 gene leading to loss of galactokinase (GALK) enzyme activity. Like patients with loss of GALT activity, patients missing GALK activity cannot fully metabolize galactose so that if they consume a diet high in lactose/galactose they will accumulate high levels of galactose and galactose metabolites including galactitol and presumably galactonate, though this metabolite is rarely measured. Unlike patients who are missing GALT activity, patients with galactokinase deficiency do not accumulate high levels of Gal-1P because GALK is the enzyme that synthesizes Gal-1P.
Galactokinase deficiency is very rare in many populations and is not detected by many newborn screening programs so that long-term follow-up studies of large numbers of patients diagnosed with galactokinase deficiency have been difficult to conduct. Because those patients with galactokinase deficiency studied were ostensibly well as infants, except for cataracts that self-resolved following dietary galactose restriction, loss of galactokinase was believed to be relatively benign regardless of diet. That assumption was challenged in 2011 when Hennermann and colleagues (J Inherit Metab Dis (2011) 34:399–407) reported the identification and follow-up of 18 patients with galactokinase deficiency detected in Germany by newborn screening between 1991 and 2010. Almost half of these patients were of Romani ancestry, a population believed to have significantly increased prevalence of GALK deficiency relative to other populations studied.
What was striking about these patients is that despite their early detection, of the 16 who were old enough to be evaluated, 31% demonstrated what was described as "mental retardation" attributed to "poor compliance" with dietary galactose restriction. The negative outcomes noted did not associate with consanguinity in these families. This result raises the strong possibility that accumulation of galactose metabolites, other than Gal-1P, in these patients contributed to their increased risk of intellectual disability.
Newborns with galactokinase deficiency may or may not be detected by the newborn screening test for galactosemia. Specifically, some newborn screening protocols are designed to detect galactokinase deficiency, while others are not. Receiving a “normal” newborn screening result for galactosemia therefore may not rule out a diagnosis of galactokinase deficiency.
Links:
https://en.wikipedia.org/wiki/Galactokinase_deficiency
http://www.omim.org/entry/230200
http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=79237
Info from http://www.galactosemia.org/understanding-galactosemia/#GKD
Galactokinase deficiency results from inheritance of deleterious mutations in the human GALK1 gene leading to loss of galactokinase (GALK) enzyme activity. Like patients with loss of GALT activity, patients missing GALK activity cannot fully metabolize galactose so that if they consume a diet high in lactose/galactose they will accumulate high levels of galactose and galactose metabolites including galactitol and presumably galactonate, though this metabolite is rarely measured. Unlike patients who are missing GALT activity, patients with galactokinase deficiency do not accumulate high levels of Gal-1P because GALK is the enzyme that synthesizes Gal-1P.
Galactokinase deficiency is very rare in many populations and is not detected by many newborn screening programs so that long-term follow-up studies of large numbers of patients diagnosed with galactokinase deficiency have been difficult to conduct. Because those patients with galactokinase deficiency studied were ostensibly well as infants, except for cataracts that self-resolved following dietary galactose restriction, loss of galactokinase was believed to be relatively benign regardless of diet. That assumption was challenged in 2011 when Hennermann and colleagues (J Inherit Metab Dis (2011) 34:399–407) reported the identification and follow-up of 18 patients with galactokinase deficiency detected in Germany by newborn screening between 1991 and 2010. Almost half of these patients were of Romani ancestry, a population believed to have significantly increased prevalence of GALK deficiency relative to other populations studied.
What was striking about these patients is that despite their early detection, of the 16 who were old enough to be evaluated, 31% demonstrated what was described as "mental retardation" attributed to "poor compliance" with dietary galactose restriction. The negative outcomes noted did not associate with consanguinity in these families. This result raises the strong possibility that accumulation of galactose metabolites, other than Gal-1P, in these patients contributed to their increased risk of intellectual disability.
Newborns with galactokinase deficiency may or may not be detected by the newborn screening test for galactosemia. Specifically, some newborn screening protocols are designed to detect galactokinase deficiency, while others are not. Receiving a “normal” newborn screening result for galactosemia therefore may not rule out a diagnosis of galactokinase deficiency.
Links:
https://en.wikipedia.org/wiki/Galactokinase_deficiency
http://www.omim.org/entry/230200
http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=79237
