Novel Mutation in GALT Gene in Galactosemia Patient with Group B Streptococcus Meningitis and Acute Liver Failure

Abstract

Classic galactosemia is an autosomal recessive disorder caused by the deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT) involved in galactose metabolism. Bacterial infections are a known cause of early morbidity and mortality in children with classic galactosemia. The most common agent is Escherichia coli, but in rare situations, other bacteria are incriminated. We report a case of a three-week-old female patient with galactosemia, who presented with Group B Streptococcus (GBS) meningitis/sepsis. She received treatment with antibiotics, supportive therapy, and erythrocyte transfusion, but after a short period of improvement, she presented acute liver failure with suspicion of an inborn error of metabolism. Rapid nuclear magnetic resonance (NMR) spectroscopy from urine showed highly elevated values of galactose and galactitol. Under intensive treatment for acute liver failure and with a lactose-free diet, her clinical features and laboratory parameters improved considerably. Genetic testing confirmed compound heterozygous status for GALT mutations: c.563 A>G [p.Q188R] and c. 910 C>T, the last mutation being a novel mutation in GALT gene. In countries without an extensive newborn screening program, a high index of suspicion is necessary for early diagnosis and treatment of galactosemia.

Etiology and Outcome of Acute Liver Failure in Children—The Experience of a Single Tertiary Care Hospital from Romania

“…Furthermore, ALF etiology in children varies according to geographical areas and socio-economic conditions. In developing countries, toxics are the first cause of ALF, while in countries with a low socio-economic level, infections, especially with hepatitis A (HAV) and B (HBV) virus, are the main causes [ 10 , 11 ]. Although ALF in children is a rare condition, it results in a high mortality rate in the absence of an emergency liver transplant.…”

Vitamin D-Binding Protein (Gc-Globulin) in Acute Liver Failure in Children

“…Clichy-Villejuif Criteria, with factor V levels as the main parameter, are used to decide the need for emergency liver transplant in ALF [5,[7][8][9]. However, none of these factors accurately predict possible negative evolution of ALF patients [6,7,[28][29][30][31][32]; new markers should be studied to earlier predict the evolution of liver cell injuries.…”

Monitoring Methylmalonic Aciduria by NMR Urinomics

“…The 1 H-NMR spectra were recorded with NOSEY water presaturation. For initial diagnosis the NMR spectra have been recorded at 400 MHz in quantitative conditions with a pulse sequence using 32 scans, a 90° pulse, 30 s relaxation delay, 3 s CW irradiation, and 4 s acquisition time as previously described [ 14 , 15 , 16 , 17 , 20 , 76 ]. The second NMR analysis on another aliquot was performed at 600 MHz with pulse sequences and parameters as delivered with Bruker Biospin IVDr methods (V.2.0), which allow fast acquisition of 1 H-NMR spectra using 32 scans, a 90° pulse, 4 s relaxation delay with simultaneous CW irradiation, and 2.7 s acquisition time with an ERETIC type of signal as the quantitation reference and J-Resolved NMR spectra for signal assignment support (4 min total experimental time for each type of spectrum) [ 77 ].…”

“…The same group also described the comparison of metabolite concentrations for control populations from two different geographical regions [ 13 ]. We also published metabolite concentrations for normal and diabetes groups from Eastern Europe (Bucharest), and we discussed the results in comparison with previously published data [ 14 , 15 ]—our interests covering diagnoses of various metabolic disorders [ 16 , 17 , 18 , 19 ].…”