Correlates of language impairment in children with galactosaemia

Abstract

Summary Purpose This study describes risk factors associated with language impairment in children with classic galactosaemia. Method Thirty-three 4–16-year-old participants with classic galactosaemia and a history of speech sound disorders completed a battery of cognitive and language measures and their parents completed a family history questionnaire. Results Nine of the sixteen (56%) participants with typical cognitive development and 15 of the 17 (88%) with borderline-low cognitive development had language impairments. Participants with typical cognitive development more often had an expressive language disorder, whereas those with borderline-low cognitive development more often had a mixed receptive-expressive language disorder. Participants with Q188R/Q188R genotypes had increased risk for both cognitive and language impairments. The IQs of younger siblings who did not consume milk postnatally were 10–56 points higher than the IQs of their older siblings with galactosaemia who had consumed milk postnatally. However, 4 of 5 younger siblings who were lactose-restricted from birth had language impairments. Typically-reported risk factors for language disorder, including parental history of speech/learning problems and low parental education level, were not significantly associated with cognitive or language impairments in the present sample of children with galactosaemia. Conclusions Children with galactosaemia and speech disorders have a 4–6 times greater risk for language impairment than children with early speech disorders of unknown origin. Early dietary lactose may increase the risk for cognitive and language impairments; however, the lack of significant associations of language impairment with days of milk consumption, and other familial and educational risk factors, is consistent with prenatal causation.

Classical Galactosaemia and CDG, the N-Glycosylation Interface. A Review

“…Overall, speech and language Glycosylation-type II, CDG-II). Blue arrows for ALG9 (Alpha-1, 2-mannosyltransferase), MGAT1 and MGAT3 represent respective gene expression pattern observed in our recent study (Maratha et al 2016) disorders are estimated to affect at least 25% of individuals with galactosaemia, commonly presenting in childhood (Schweitzer et al 1993;Potter et al 2008Potter et al , 2013Timmers et al 2012;Waisbren et al 2012;Coss et al 2013), with pathophysiological correlates studied in fMRI brain studies (Timmers et al 2015).…”

Cross‐sectional analysis of speech and cognitive performance in 32 patients with classic galactosemia

“…Affected newborns develop a potentially lethal hepatotoxic syndrome ascribed to high concentrations of galactose-1-phosphate, which usually resolves rapidly after the institution of a lactose-free diet. In contrast to the rapid recovery of liver disease, long-term outcome in classic galactosemia remains disappointing: Despite strict adherence to the lactose-free diet, a great percentage of patients have impaired cognitive performance (Antshel et al 2004;Fishler et al 1980;Hansen et al 1996;Schadewaldt et al 2010;Kaufman et al 1994;Komrower and Lee 1970;Nelson et al 1991;Potter et al 2008;Scheibenreiter et al 1992;Schweitzer et al 1993;Shield et al 2000;Waggoner et al 1990), motor function disturbances (Kaufman et al 1995;Schweitzer et al 1993), and reduced bone mineral density (Panis et al 2004). More than 80% of adult females suffer from hypergonadotropic hypogonadism (Forges et al 2006;Kaufman et al 1979;Liu et al 2000).…”

“…Despite the considerable number of publications on speech impairment in galactosemia, in only a few studies validated tests for evaluation of speech performance have been applied (Hansen et al 1996;Kaufman et al 1995;Potter et al 2008;Robertson and Singh 2000;Waisbren et al 1983;Webb et al 2003), and only limited information on the specific pattern of speech impairment is available (Nelson et al 1991). In addition, there are conflicting views on the relationship between speech impairment and cognition in galactosemia (Kaufman et al 1995;Potter et al 2008;Waisbren et al 1983).…”

Introduction to the Maastricht workshop: lessons from the past and new directions in galactosemia

“…Furthermore, these late-onset apparent diet-independent complications occurred even if diet therapy began on day 1 of life (Waggoner et al 1990;Hughes et al 2009). In addition to the above well known diet-independent complications (Nelson et al 1991;Schweitzer et al 1993;Guerrero et al 2000;Robertson et al 2000;Webb et al 2003;Gubbels et al 2008;Berry 2008;Potter et al 2008), we now know that additional complications include poor growth and/or short stature, reduced bone mineral density, deficits in personality construct, mood disorder, tremor, cerebellar ataxia and extrapyramidal movement disorders (Kaufman et al 1993;Rubio-Gozalbo et al 2002;Leslie 2003;Bosch 2006;Panis et al 2007). In some instances, discrete neurological, imaging and neuropathological findings have been recorded (Crome 1962;Huttenlocher et al 1970;Haberland et al 1971;Jan and Wilson 1973;Nelson et al 1992;Belman et al 1986;Bohles et al 1986;Koch et al 1992;Kaufman et al 1995;Ridel et al 2005;Hughes et al 2009).…”