Hand fine motor control in classic galactosemia

Abstract

Classic galactosemia (CG) is a rare inborn error of metabolism that results from profound deficiency of galactose-1-P uridylyltransferase (GALT). Despite early detection and rapid and lifelong dietary restriction of galactose, which is the current standard of care, most patients grow to experience a broad range of complications that can include motor difficulties. The goal of this study was to characterize hand fine motor control deficit among children and adults with classic galactosemia (CG). Specifically, we used Neuroglyphics software to collect digital Archimedes spiral drawings on a touch screen from 57 volunteers with CG (cases) and 80 controls. Hand fine motor control was scored as root mean square (RMS) of spirals drawn relative to an idealized template. Presence of tremor was defined as a peak in periodicity of changes in drawing speed or direction in the 4-8 Hz range. We observed a highly significant difference (P < .001) in RMS scores between cases and controls, with almost 51% of cases showing at least 1 of 4 spirals scoring outside the 95th percentile for controls.The corresponding prevalence for controls was 10%. Similarly, more than 35% of cases, and almost 14% of controls, showed at least 1 of 4 spirals with a tremor amplitude above the 95th % cutoff for controls. Our results both confirm and extend what is known about hand fine motor control deficit among children and adults with CG and establish digital assessment as a useful approach to quantify this outcome.

Novel mRNA therapy restores GALT protein and enzyme activity in a zebrafish model of classic galactosemia

“…[13][14][15][16] The current standard of care, a galactoserestricted diet, quickly resolves the neonatal illness but fails to prevent chronic impairments affecting the brain and gonads. 17,18 In recent years, treatments that target the GALT enzyme deficiency itself have been investigated. Several disease-causing variants negatively affect protein folding and stability of the GALT protein 19,20 and pharmacological/chemical chaperones have been shown to rescue variant proteins.…”

“…CG presents as a life‐threatening disease in the neonatal period upon exposure to galactose‐containing milk affecting thousands of patients worldwide 13–16 . The current standard of care, a galactose‐restricted diet, quickly resolves the neonatal illness but fails to prevent chronic impairments affecting the brain and gonads 17,18 . In recent years, treatments that target the GALT enzyme deficiency itself have been investigated.…”

Brain function in classic galactosemia, a galactosemia network (GalNet) members review

“…Approximately half of the CG patients suffer from neurological complications, the most prevalent being tremor (31.0%), which may affect daily life in some cases ( Rubio-Gozalbo et al, 2019 ). Other complications include general motor abnormalities, ataxia, dystonia and epilepsy ( Jan and Wilson, 1973 ; Lo et al, 1984 ; Bohles et al, 1986 ; Friedman et al, 1989 ; Waggoner et al, 1990 ; Koch et al, 1992 ; Schweitzer et al, 1993 ; Robertson et al, 2000 ; Arn, 2003 ; Antshel et al, 2004 ; Martins et al, 2004 ; Ridel et al, 2005 ; Potter et al, 2008 ; Hughes et al, 2009 ; Shah and Kuchhai, 2009 ; Waisbren et al, 2012 ; Rubio-Agusti et al, 2013 ; Demirbas et al, 2019 ; Kuiper et al, 2019 ; Rubio-Gozalbo et al, 2019 ; Welling et al, 2019 ; Özgün et al, 2019 ; Welsink-Karssies et al, 2020a ; MacWilliams et al, 2021 ). Epilepsy is not frequently reported ( Friedman et al, 1989 ; Aydin-Ozemir et al, 2014 ) and may be the result of brain damage occurring in the neonatal period, or the consequence of unrelated genetic predisposition.…”