Neonatal classic galactosemia—diagnosis, clinical profile and molecular characteristics in unscreened Turkish population

Abstract

Background Classic galactosemia (CG) is a rare hereditary disease that can cause serious morbidity and death if it is not diagnosed and treated in early periods of life. Clinical findings usually occur in the neonatal period after the neonate is fed with milk that contains galactose. Most patients are presented with jaundice, hepatomegaly, hypoglycemia and cataracts. Objective We aimed to document the clinical, molecular characteristics, regional estimated incidence and time of diagnosis in newborn with CG. Materials and method The data of 63 newborn with CG who were diagnosed and followed up between January 2011 and January 2018 were analyzed retrospectively. Results During the study period, 63 (33 boys and 30 girls) newborns were diagnosed with CG. The median gestational age was 39 weeks (33–42). Major presenting symptoms were jaundice 90.5% and cataract 41.2%. The mean age at first symptom was 12 ± 7.4 days while the mean age at diagnosis was 18.9 ± 10.6 days. Nearly half of the patients (55.5%) were diagnosed later than the postnatal 15th day. Genetic analysis was performed on 56 patients and homozygous Q188R mutation was found in 92.8%. There were signs of sepsis in 33.3% of the cases. Six patients died due to sepsis. There was consanguinity in 84.1% of the parents and regional estimated incidence was calculated as 1 in 6103 live births. Conclusion Q188R mutation was found in 92.8% of our cases. The regional estimated incidence was found as 1 in 6103 live births. Our study strongly supports that galactosemia should be included in the national newborn screening program.

Genetic aetiologies of acute liver failure

“…Galactose-1-phosphate uridylyltransferase deficiency caused by mutations in GALT is the cause of classic galactosaemia. Newborns present with jaundice, hepatomegaly, coagulopathy, poor feeding, hypoglycaemia and cataracts 32 and is one of the main differential diagnoses for ALF in this age group. 33,34 Urgent removal of galactose from the diet is necessary as soon as the diagnosis is suspected and, if positive, there is an initial slowing of liver dysfunction followed by a full recovery.…”

Classic Galactosemia: Clinical and Computational Characterization of a Novel GALT Missense Variant (p.A303D) and a Literature Review

“…The GALT gene is located on chromosome 9p13 and comprises 11 exons [6]. To date, more than 350 GALT alterations have been reported, most of which are missense pathogenic variants [7,8]. Several disease-causing variants negatively impact GALT protein folding and stability [9].…”

“…Several disease-causing variants negatively impact GALT protein folding and stability [9]. In the European population, the most common missense variants are c.563A>G (p.Q188R) and c.855G>T (p.K285N), both of which have been associated with low GALT activity and poor prognosis [7]. Besides disease-causing variants, several GALT gene variants resulting in diverse levels of enzyme activity have been reported, including the Duarte variants (D1 and D2 alleles).…”