Molecular and clinical analysis of patients with classic and Duarte galactosemia in western Hungary

Abstract

The most serious clinical phenotypes in our population were associated with mutations p. Q188R, p.K285N, p.X380R, p.S297P, p.M142K, p.R.204X, p.Q169K and p.R407P, but manifestations depend on other genetic and environmental factors.

Galactosemia in the Turkish population with a high frequency of Q188R mutation and distribution of Duarte-1 and Duarte-2 variations

“…The frequency of the mutations (between 45 and 93.6%) was reported to be as follows in different countries: Ireland, 93.6%; 17 Great Britain, 77%; 3 Portugal, 57.8%; 18 The Netherlands, 58.5%; 19 Spain, 50%; 18 Germany, 69%; 20 Austria, 60%; 21 Poland, 51.3%; 22 the Czech Republic and the Slovak Republic, 46%; 7 and Hungary, 45%. 23 As in these European countries, it was also found to be the most common disease-causing mutation in the Turkish population, and presented data strengthen the observed pattern that the frequency of the Q188R mutation decreases from the west to the east and from the north to the south in the European continent. 24 In the present study on the Turkish population, K285N is seen only in 3.57% of the population.…”

“…The frequency of this mutant allele varies from 19 to 33.8% in different European populations. 7,[20][21][22][23] In contrast to these high frequencies observed and reported above, some populations have a low allele frequency for this mutation, with distribution between 2.4 and 9.8% in European countries. 18,19,25 These three mutant alleles, A320T (7.14%), E340* (10.71%) and M142K (6.25%), are the second in terms of frequency in Turkish patients and are observed more commonly than in other populations.…”

Appropriateness of newborn screening for classic galactosaemia: a systematic review

“…Step 5 Greber-Platzer et al 1997;Itemetal.2002;Kozak et al 2000;Milankovics et al 2010;Murphyetal.1999;Ng et al 1994;Ounap et al 2010;Suzuki et al 2001;Tyfield et al 1999;V i g g i a n oe ta l .2015; Zekanowski et al 1999 (Kozak et al 2000;Milankovics et al 2010;Zekanowskietal.1999). Two studies coming from these countries showed that subjects homozygous for p.Q188R or p.K285N exhibit nil enzyme activity, severe newborn symptoms and long-term complications.…”

“…Duarte 2, variant galactosaemia (heterozygocity for the Duarte muation p. Asn314Asp (pN314D) and a classic galactosaemia allele), were found in 2-15 % of populations (Greber-Platzer et al 1997;Kozak et al 2000;Milankovics et al 2010;Suzuki et al 2001). Patients with Duarte 2 galactosaemia presented reduced enzyme activity (≤25 %) and 0 or mild symptomatology and good long-term prognosis in the study performed by Milankovics et al (2010). This study identified two siblings with p.Gln188Arg/ p.Glu146Asp heterozygous genotypes, who also showed approximately 25 % of normal activity and mild symptomatology.…”

“…Schweitzer et al (1993)alsoreported that exchange transfusion was necessary in 36 % of the 134 patients identified in 25 children's hospitals in Germany (30 %-40 % potential number of galactosaemia cases). In Hungary (Milankovics et al 2010) and Italy (Viggiano et al 2015) > 90 % of newborns presented symptomatology before screening (day 4-5), 72.7 % of a severe nature. In Estonia, the mean age at hospitalisation of the nine symptomatic cases detected through screening was 12 days, with final diagnosis at 19 days (Ounap et al 2010).…”