Objective: The observed irregularities in the biochemical profile and the limited information on long-term outcomes among patients with Duarte variant (D/G) galactosemia have led to patient management variability. This study examined the molecular characteristics of Filipino patients with presumed variant galactosemia for confirmation of diagnosis. It also aimed to describe the corresponding biochemical, clinical and neurodevelopmental profiles in order to gain a better understanding of the patients with normal galactose metabolites in spite of low to absent GALT activity detected by the local newborn screening program. Methods: Thirteen (13) patients who were presumed to have a variant form of galactosemia by national newborn screening between 2002 and 2010, and who previously underwent physical and neurodevelopmental assessment were included in the study. Repeat clinical, ophthalmologic and neurodevelopmental evaluations were done upon recruitment of participants. Direct sequence analysis of the coding region of the GALT gene was conducted to determine the patients’ genotypes. Results: None of the patients’ genotypes were consistent with Duarte variant (D/G) galactosemia. Their genotypes reflect the normal total blood galactose levels in patients, but were inconsistent with the absent or trace GALT activity. Conclusion Molecular testing for the entire cohort of presumed “variant” galactosemia Filipino patients will provide better profiling of this condition. Re-evaluation and assessment of the current guidelines used by national newborn screening in classifying variant galactosemia are recommended.
Galactosemias ; Neonatal Screening

No abstract available.
Galactitol* ; Galactosemias* ; Humans ; Infant* ; Mass Screening*

The trial of external quality assessment for inborn error of metabolism was performed in 2003. A total 10 specimens for neonatal screening tests were distributed to 43 laboratories with a response rate of 83%. All the control materials were sent as a filter paper form. Each laboratory replied the test result as the screening items they were doing as a rountine test at the reception of the specimen among PKU screening, neonatal TSH, neonatal T4(total/free), galactosemia screen, homocytinuria screen and histidinemia screen. The mean, SD, and CV were analyzed.
Galactosemias ; Infant, Newborn ; Korea* ; Mass Screening ; Metabolism* ; Neonatal Screening

Galactosemia is a rare autosomal recessive disorder caused by the deficiency of galactose-1-phosphate uridyltransferase (GALT) enzyme activity. Classic galactosemia (G/G) is due to severe GALT deficiency in the presence of a GALT gene mutation, whereas Duarte variant (D/D) has 50% of normal GALT activity and benign clinical course. The D2 allele of Duarte variant is linked to a promoter deletion 5' to the translation start site (-119 to -116 delGTCA) in addition to N314D. So, Duarte variant/classical galactosemia (D/G) compound heterozygotes have relatively mild clinical manifestation than classical galactosemia and can be differentiated from classical galactosemia or Duarte variant by mutational analysis. We report a case of D/G galactosemia compound heterozygote proven by the reduction of GALT enzyme activity in erythrocytes and mutation analysis of GALT gene, which revealed N314D polymorphism and -119 to -116 delGTCA.
Alleles ; Erythrocytes ; Galactosemias* ; Heterozygote* ; UTP-Hexose-1-Phosphate Uridylyltransferase*

Galactosemia is an inborn error of galactose metabolism, caused by an abnormality in the conversion of galactose and uridine diphosphoglucose to glucose-1-phosphate and uridine diphosphogalactose through the action of 3 sequential enzymes: galactokinase (GALK), galactose- 1-phosphate uridyltransferase (GALT), and uridine phosphogalactose 4-epimerase (GALE). The advent of newborn screening brought hope with early diagnosis and prompt treatment. Newborn screening advocates have pushed for inclusion of galactosemia in the newborn screening panel. However, reports of complications despite early treatment have questioned the merits of universal screening. This paper presents issues in favour and against universal newborn screening for galactosemia.
Galactosemias ; diagnosis ; Humans ; Infant, Newborn ; Neonatal Screening ; standards

BACKGROUND

Newborns screened positive for Galactosemia through Expanded Newborn Screening (ENBS) with borderline levels undergo lactose challenge that requires interruption of breastfeeding temporarily then shifting to soy-based formula.

To determine the percentage of Classical Galactosemia (CGal), Non-classical Galactosemia (NCGal), probable mild variant form, and negative Galactosemia among newborns screened positive for Galactosemia who underwent lactose challenge.

This is a retrospective study. NBS records were reviewed and data were collected from January 2015 to December 2020.

Out of the 117 newborns screened positive for Galactosemia, 58 underwent lactose challenge. Majority were male, term with a birth weight of 2500-4000g and received a final disposition in 4-6 months. Fifteen patients underwent 1-week lactose challenge wherein six reached a resolution on first challenge. Majority, 35 (60.3%) were negative for Galactosemia, six (10.3%) probable mild variant Galactosemia, three (5.2%) NCGal, and no CGal were observed. Fourteen suspected cases (24.1%) are pending final disposition.

This study describes the demographics of newborns flagged for Galactosemia who underwent lactose challenge. A 1-week lactose challenge may be recommended to further detect patients who are negative for Galactosemia.

The trial of external quality assessment for inborn error of metabolism was performed in 2002. Total 10 specimens for neonatal screening tests were distributed to 61 laboratories with a response rate of 70.5%(43/61). All the control materials were sent as filter paper forms. Each laboratory replied the test results as the screening items they were testing routinely at the reception of the specimen among PKU screening, TSH, T4 (total/free), galactosemia screen, maple syrup urine disease screen, homocytinuria screen and histidinemia screen. The mean, SD, CV, median and range were analyzed.
Galactosemias ; Infant, Newborn ; Korea* ; Maple Syrup Urine Disease ; Mass Screening ; Metabolism* ; Neonatal Screening

Galactosemia, a term that denotes the presence of galactose in the blood, is the name of rare inborn error of galactose metabolism due to a deficiency of the enzyme galactokinase (GALK), galactose-1-phosphate uridyltransferase (GALT) and uridine diphosphate-galactose 4-epimerase (GALE). GALT deficiency is the most common and shows the most severe clinical manifestation, including hepatomegaly, cataracts, and mental retardation. The main symptom of GALT deficiency is juvenile cataracts. GALE deficiency has two different forms; benign and severe forms. The benign form has no clinical significance, however, the severe form shows the same clinical manifestations as those of GALT deficiency.
Cataract ; Galactokinase ; Galactose ; Galactosemias* ; Hepatomegaly ; Intellectual Disability ; Metabolism ; Uridine ; UTP-Hexose-1-Phosphate Uridylyltransferase

OBJECTIVE: This study reviewed the profiles and outcomes of patients diagnosed to have the five most common inherited metabolic diseases (IMDs) in the Metabolic Registry of the National Institutes of Health - Institute of Human Genetics (NIH-IHG) from 1999 to 2016.

METHODS: The medical records of the patients diagnosed with the following inherited metabolic diseases were reviewed: maple syrup urine disease (MSUD), galactosemia, hyperphenylalaninemias (including classical phenylketonuria, mild hyperphenylalaninemia, and pterin defects), mucopolysaccharidoses (MPS), and adrenoleukodystrophy (ALD).

RESULTS: There was a total of 567 patients with IMDs, giving a minimum estimated burden of 1.9 per 100,000 livebirths (1:51,760). Clinical presentations were similar to those reported in literature. Majority of the cases of galactosemia and hyperphenylalaninemias presented with a positive newborn screening result. The local prevalence of MSUD and MPS II were higher compared to international data, which may be explained by reported founder mutations among Filipinos. Majority of the patients with IMDs were diagnosed late leading to preventable developmental delay or intellectual disability and death. Majority of patients with MSUD (80.6%) and MPS (94.7%) had intellectual disability or developmental delay. Mortality was 50.5% among patients with MSUD and 100% among patients with adrenoleukodystrophy.

CONCLUSION: There is a diversity of IMDs present in the country. A long-term strategic plan, such as the full implementation of the National Rare Disease Act, is foreseen to improve access to comprehensive healthcare and quality of life of patients with IMDs in the country.

OBJECTIVE: To explore the clinical features and genetic basis of a child with Galactosemia. METHODS: A child who had presented at the Children's Hospital Affiliated to Zhengzhou University on November 20, 2019 was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variants were validated by Sanger sequencing. RESULTS: Clinical manifestations of the child have included anemia, feeding difficulty, jaundice, hypomyotonia, abnormal liver function and coagulation abnormality. Tandem mass spectrometry showed increased citrulline, methionine, ornithine and tyrosine. Urine organic acid analysis showed increased phenyllactic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenyllactic acid, 4-hydroxyphenylpyruvate and N-acetyltyrosine. Genetic testing revealed that the child has harbored compound heterozygous variants of the GALT gene, namely c.627T>A (p.Y209*) and c.370G>C (p.G124R), which were respectively inherited from her healthy parents. Among these, c.627T>A (p.Y209*) was known as a likely pathogenic variant, while c.370G>C (p. G124R) was unreported previously and also predicted as a likely pathogenic variant(PM1+PM2_Supporting+PP3_Moderate+PPR). CONCLUSION Above discovery has expanded the spectrum of the GALT gene variants underlying Galactosemia. Patients with thrombocytopenia, feeding difficulties, jaundice, abnormal liver function and coagulation abnormality without obvious causes should be analyzed by screening of metabolic diseases in combination with genetic testing.
Child ; Female ; Humans ; Galactosemias/genetics* ; Genetic Testing ; Health Status ; Methionine ; Muscle Hypotonia ; Mutation