Galactokinase deficiency:lessons from the GalNet registry

PURPOSE Galactokinase (GALK1) deficiency is a rare hereditary galactose metabolism disorder. Beyond cataract, the phenotypic spectrum is questionable. Data from affected patients included in the Galactosemias Network registry were collected to better characterize the phenotype. METHODS Observational study collecting medical data of 53 not previously reported GALK1 deficient patients from 17 centers in 11 countries from December 2014 to April 2020. RESULTS Neonatal or childhood cataract was reported in 15 and 4 patients respectively. The occurrence of neonatal hypoglycemia and infection were comparable with the general population, whereas bleeding diathesis (8.1% versus 2.17-5.9%) and encephalopathy (3.9% versus 0.3%) were reported more often. Elevated transaminases were seen in 25.5%. Cognitive delay was reported in 5 patients. Urinary galactitol was elevated in all patients at diagnosis; five showed unexpected Gal-1-P increase. Most patients showed enzyme activities ≤1%. Eleven different genotypes were described, including six unpublished variants. The majority was homozygous for NM_000154.1:c.82C>A (p.Pro28Thr). Thirty-five patients were diagnosed following newborn screening, which was clearly beneficial. CONCLUSION The phenotype of GALK1 deficiency may include neonatal elevation of transaminases, bleeding diathesis, and encephalopathy in addition to cataract. Potential complications beyond the neonatal period are not systematically surveyed and a better delineation is needed

Partitioning of Large-Scale and Local-Scale Precipitation Events by Means of Spatio-Temporal Precipitation Regimes on Corsica

The island of Corsica in the western Mediterranean is characterized by a pronounced topography in which local breeze systems develop in the diurnal cycle. In interaction with the large-scale synoptic situation, various precipitation events occur, which are classified in this study with regard to their duration and intensity. For this purpose, the island was grouped into five precipitation regimes using a cluster analysis, namely the western coastal area, the central mountainous region, the southern coastal area, the northeast coastal area, and the eastern coastal area. Based on principal component analysis using mean sea level pressure (mslp) obtained from ERA5 reanalysis (the fifth generation of the European Centre for Medium-Range Weather Forecasts, ECMWF), six spatial patterns were identified which explain 98% of the large-scale synoptic situation, while the diurnal breeze systems within the regimes characterize local drivers. It is shown that on radiation days with weak large-scale pressure gradients, pronounced local circulations in mountainous regions are coupled with sea breezes, leading to a higher number of short and intense precipitation events. Meridional circulation patterns lead to more intensive precipitation events on the eastern part of the island (30% intensive events with meridional patterns on the east side compared to 11% on the west side). On the west side of Corsica, however, coastal precipitation events are seldom and less intense than further inland, which can be attributed to the influence of the topography in frontal passages

Oxygen and hydrogen stable isotopic composition of precipitation, creek, and underground water on Corsica (France) 2017-2019

In this study several water compartments (precipitation, creek, soil) were sampled over a two-year period on a bi-weekly basis from April 2017 to April 2019 and analyzed for the temporal variations of their oxygen and hydrogen stable isotope ratios (δ18O and δ2H) at five sites over an elevation gradient from sea level to around 1600 m a.s.l. on the Mediterranean island of Corsica (France). Sampling site code is composed of the mountain ridge side (W for west, E for east) and the approximate elevation (L for low, M for mid, H for high). Precipitation was collected via evaporation-free, tube-dip-in water precipitation collectors (Palmex d.o.o., Zagreb, Croatia). Creek water samples were taken mid-stream. Where possible, soil suction probes were installed at around 80 to 100 cm depth. If the topsoil layers were too thin or rocky and a soil probe installment was not possible, water from roadside springs and fountains, or rockface seeps was sampled. Probe, fountain, and seep water are referred to as 'underground' water

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

Classic galactosemia (CG, OMIM #230400, ORPHA: 79,239) is a hereditary disorder of galactose metabolism that, despite treatment with galactose restriction, affects brain function in 85% of the patients. Problems with cognitive function, neuropsychological/social emotional difficulties, neurological symptoms, and abnormalities in neuroimaging and electrophysiological assessments are frequently reported in this group of patients, with an enormous individual variability. In this review, we describe the role of impaired galactose metabolism on brain dysfunction based on state of the art knowledge. Several proposed disease mechanisms are discussed, as well as the time of damage and potential treatment options. Furthermore, we combine data from longitudinal, cross-sectional and retrospective studies with the observations of specialist teams treating this disease to depict the brain disease course over time. Based on current data and insights, the majority of patients do not exhibit cognitive decline. A subset of patients, often with early onset cerebral and cerebellar volume loss, can nevertheless experience neurological worsening. While a large number of patients with CG suffer from anxiety and depression, the increased complaints about memory loss, anxiety and depression at an older age are likely multifactorial in origin

Galactokinase deficiency: lessons from the GalNet registry

PURPOSE: Galactokinase (GALK1) deficiency is a rare hereditary galactose metabolism disorder. Beyond cataract, the phenotypic spectrum is questionable. Data from affected patients included in the Galactosemias Network registry were collected to better characterize the phenotype. METHODS: Observational study collecting medical data of 53 not previously reported GALK1 deficient patients from 17 centers in 11 countries from December 2014 to April 2020. RESULTS: Neonatal or childhood cataract was reported in 15 and 4 patients respectively. The occurrence of neonatal hypoglycemia and infection were comparable with the general population, whereas bleeding diathesis (8.1% versus 2.17-5.9%) and encephalopathy (3.9% versus 0.3%) were reported more often. Elevated transaminases were seen in 25.5%. Cognitive delay was reported in 5 patients. Urinary galactitol was elevated in all patients at diagnosis; five showed unexpected Gal-1-P increase. Most patients showed enzyme activities ≤1%. Eleven different genotypes were described, including six unpublished variants. The majority was homozygous for NM_000154.1:c.82C>A (p.Pro28Thr). Thirty-five patients were diagnosed following newborn screening, which was clearly beneficial. CONCLUSION: The phenotype of GALK1 deficiency may include neonatal elevation of transaminases, bleeding diathesis, and encephalopathy in addition to cataract. Potential complications beyond the neonatal period are not systematically surveyed and a better delineation is needed.status: publishe