Early neurological complications in children with classical galactosemia and p.gln188arg mutation

Abstract

Background Despite implementation of a controlled diet, children with classical galactosemia (CG) may develop a variety of developmental and cognitive problems. In this study, we examined the early developmental status of, as well as the neurological and neuroradiological findings for, children with CG. Methods We retrospectively evaluated 46 galactosemia patients who were followed between 2003 and 2017. We included those who exhibited CG and p.gln188arg homozygous mutation without concomitant disease and who had undergone detailed neurological examination, brain magnetic resonance imaging (MRI), and Denver II developmental testing. Results The mean ages at the time of the most recent neurological examination and Denver II testing were 48.5 ± 28.5 months and 34.4 ± 18.2 months, respectively. Developmental delay was defined as developmental age ≥ 20% lower than chronological age. The results were normal in 25 patients and delayed ≥ 20% in least in one domain, primarily in language development, in 21 patients. Brain MRI was abnormal in 22 patients. Conclusions This analysis of the youngest children with the same genetic mutation reported thus far showed that, despite treatment, developmental delays and abnormalities on brain MRI may begin at an early age.

Severe galactosemia of type 1 in a premature baby: difficulties of differential diagnosis

“…С внедрением скрининга в Российской Федерации появилась возможность постановки диагноза еще до момента появления первых признаков заболевания. Вместе с тем у недоношенных детей скрининг проводится в более поздние сроки, что в совокупности с неспецифическим характером начальных проявлений может привести к поздней диагностике заболевания [28]. В рассмотренном нами клиническом случае ребенок родился недоношенным и получал энтеральное питание, преимущественно смесью для недоношенных детей с пониженным содержанием лактозы и галактозы.…”

“…Анализируя особенности течения болезни у данного ребенка, следует также отметить появление менингеальных знаков в начале заболевания, что на фоне гипертермии не позволяло исключить тяжелое инфекционное поражение ЦНС. Однако данная симптоматика достаточно характерна и для кризового течения галактоземии I типа [23,28]. Рассмотренный нами клинический случай галактоземии I типа у недоношенного ребенка демонстрирует неспецифические проявления в дебюте заболевания, которые могут скрываться под маской других патологических состояний, весьма часто встречающихся в неонатальном периоде, таких как поздний неонатальный сепсис или геморрагическая болезнь новорожденных.…”

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.…”

“…Numerous central nervous system (CNS) grey and white matter abnormalities have been reported in CG ( Crome, 1962 ; Haberland et al, 1971 ; Lo et al, 1984 ; Choulot et al, 1991 ; Koch et al, 1992 ; Nelson et al, 1992 ; Kaufman et al, 1995b ; Hughes et al, 2009 ; Timmers et al, 2015b ; Timmers et al, 2016 ; Özgün et al, 2019 ; Ahtam et al, 2020 ; Welsink-Karssies et al, 2020a ; Welsink-Karssies et al, 2020c ). Magnetic resonance imaging (MRI) in a cohort of 67 patients showed cerebral and cerebellar atrophy in 22 and 8 patients, respectively, as well as white matter abnormalities in 11 patients ( Nelson et al, 1992 ).…”

“…Most have a shy and reserved personality (Antshel et al, 2004) and achieve fewer social developmental milestones when compared to healthy controls, which is postulated to be intrinsic to the disease rather than a result of the burden of a chronic disease or lifelong dietary restrictions (Bosch et al, 2009;Gubbels et al, 2011). Numerous central nervous system (CNS) grey and white matter abnormalities have been reported in CG (Crome, 1962;Haberland et al, 1971;Lo et al, 1984;Choulot et al, 1991;Koch et al, 1992;Nelson et al, 1992;Kaufman et al, 1995b;Hughes et al, 2009;Timmers et al, 2015b;Timmers et al, 2016;Özgün et al, 2019;Ahtam et al, 2020;Welsink-Karssies et al, 2020a;Welsink-Karssies et al, 2020c). Magnetic resonance imaging (MRI) in a cohort of 67 patients showed cerebral and cerebellar atrophy in 22 and 8 patients, respectively, as well as white matter abnormalities in 11 patients (Nelson et al, 1992).…”