Disorder Of Galactose Metabolism Research Articles

Measurement of temperature, pH and substrate levels on the activity of the Galactose-1-Phosphate Uridyltransferase enzyme

Galactose-1-phosphate uridyltransferase (GALT) is an important enzyme involved in galactose metabolism. Understanding the factors influencing GALT activity is critical to elucidate its physiological role and potential therapeutic implications in galactosemia. In developing new drugs, chicken intestine/liver powder can be used as an enzyme source, GALT, to treat galactosemia. Therefore, it is necessary to research the characterization of the GALT enzyme in chicken intestine and liver powder. In this study, we investigated the influence of temperature, pH, and substrate level on GALT enzyme activity using an experimental approach in vitro. The optimum pH extraction results show that the optimum pH for the extraction of the chicken intestine and liver GALT is pH 7, with activity values ​​of 0.47 units/mL and 0.3953 units/mL, respectively. The optimum temperature for the extraction of chicken intestine and liver GALT is 37℃ with substrate hydrolysis capabilities of 0.48 U/mL and 0.57 U/mL, respectively. Meanwhile, the optimum substrate content is 400x. These insights provide a valuable foundation for further research aimed at comprehensively understanding GALT function, developing targeted interventions for disorders of galactose metabolism, and possible application in the development of new drugs for galactosemia

Brain function in classic galactosemia, a galactosemia network (GalNet) members review.

Classic galactosemia (CG, OMIM #230400, ORPHA: 79,239) is a hereditary disorder of galactose metabolism that, despite treatment with galactose restriction, affects brain function in 85% of the patients. Problems with cognitive function, neuropsychological/social emotional difficulties, neurological symptoms, and abnormalities in neuroimaging and electrophysiological assessments are frequently reported in this group of patients, with an enormous individual variability. In this review, we describe the role of impaired galactose metabolism on brain dysfunction based on state of the art knowledge. Several proposed disease mechanisms are discussed, as well as the time of damage and potential treatment options. Furthermore, we combine data from longitudinal, cross-sectional and retrospective studies with the observations of specialist teams treating this disease to depict the brain disease course over time. Based on current data and insights, the majority of patients do not exhibit cognitive decline. A subset of patients, often with early onset cerebral and cerebellar volume loss, can nevertheless experience neurological worsening. While a large number of patients with CG suffer from anxiety and depression, the increased complaints about memory loss, anxiety and depression at an older age are likely multifactorial in origin.

Neuropsychological stability in classical galactosemia: A pilot study in 10 adult patients.

Classical galactosemia (CG) is an autosomal recessive disorder of galactose metabolism. Despite early initiation of a galactose-restricted diet, patients develop long-term complications including cognitive impairment. There is an ongoing debate whether the cognitive impairment in CG is stable throughout life or progresses with age. Earlier cross-sectional and longitudinal studies regarding intelligence suggest stability, but longitudinal neuropsychological studies focusing on specific cognitive functions are limited. Therefore, the aim of this study is to assess cognitive change over time in adult CG-patients. Ten adult patients with normal to borderline intelligence (mean age 33 years, range 22-49; IQ≥70 or independent work- or living situation) were assessed twice with a mean time interval of 3 years and 9 months (range 1023-1575 days). The neuropsychological assessments covered information processing speed, executive functioning, verbal fluency, and visuospatial functioning. Results showed that there was no significant decline or improvement in test scores on all neuropsychological measures except a decline on the Trail Making Test-A (p = 0.048). However, this group-level difference was subject to "regression to the mean" and was not endorsed by significant change in test scores measuring the same cognitive domain. Moreover, no specific pattern of reliable change (RCI > -1.96) was present on specific measures or within individual patients. This explorative study performed in 10 adult CG-patients with normal to borderline intelligence revealed no cognitive change on several cognitive domains. This implies that the subset of adults with a normal to borderline IQ in their early and middle adulthood are cognitively stable.

Galactose epimerase deficiency: lessons from the GalNet registry

BackgroundGalactose epimerase (GALE) deficiency is a rare hereditary disorder of galactose metabolism with only a few cases described in the literature. This study aims to present the data of patients with GALE deficiency from different countries included through the Galactosemia Network to further expand the existing knowledge and review the current diagnostic strategy, treatment and follow-up of this not well characterized entity.MethodsObservational study collecting medical data from December 2014 to April 2022 of 22 not previously reported patients from 14 centers in 9 countries. Patients were classified as generalized or non-generalized based on their genotype, enzyme activities in different tissues and/or clinical picture and professional judgment of the treating physician.ResultsIn total 6 patients were classified as generalized and 16 as non-generalized. In the generalized group, acute neonatal illness was reported in 3, cognitive and developmental delays were present in 5 and hearing problems were reported in 3. Four generalized patients were homozygous for the genetic variant NM_001008216.2:c.280G > A (p.Val94Met). In the non-generalized group, no clearly related symptoms were found. Ten novel genetic variants were reported in this study population.ConclusionThe phenotypic spectrum of GALE deficiency ranges from asymptomatic to severe. The generalized patients have a phenotype that is in line with the 9 described cases in the literature and prescribing dietary interventions is the cornerstone for treatment. In the non-generalized group, treatment advice is more difficult. To be able to offer proper counseling, in addition to red blood cell enzyme activity, genetic studies, transferrin glycoform analysis and enzymatic measurements in fibroblasts are recommended. Due to lack of facilities, additional enzymatic testing is not common practice in many centers nor a tailored long-term follow-up is performed.

Determination of the lactose and galactose content of common foods: Relevance to galactosemia.

Classical galactosemia (CG) is a disorder of galactose metabolism which results from deficiency of the enzyme galactose-1-phosphate uridylyl transferase (GALT). Treatment consists of immediately eliminating galactose from the diet in the new-born and lifelong restriction of dietary galactose. The inclusion of a wider variety of foods for people with CG may provide many benefits, including improved nutritional adequacy and quality of life. Galactose plays an important role in glycosylation of glycoproteins and glycolipids. Moderate liberalization of galactose restriction has been shown to improve immunoglobulin G (IgG) glycosylation for some individuals with CG. Moreover, recent outcome research suggests that strict restriction of nondairy galactose may have more unfavorable outcomes than moderate liberalization in CG patients. In the current work, based on patient feedback, we have analyzed the lactose and galactose content of different foods available in Ireland. These include a range of cheeses, yogurts, pizzas, soups, biscuits, cakes, pastries, crackers, mayonnaises, salad creams, fat spreads, crisps, corn chips, salamis, and gravies. This work provides information to support the development of a practical food-based approach to facilitate analysis of dietary galactose intake and to possibly increase overall variety of food choices for people with CG.

Newborn Screening for Classic Galactosemia: Biochemical Testings, Challenges, and Future

Galactosemia is a group of hereditary disorders of galactose metabolism. Newborn screening for galactosemia type I is mandatory in all states in the US since timely intervention can prevent life-threatening sequela. The biochemical basis, clinical presentation, and potential treatment options for different types of galactosemia are described. This review has a focus on the screening methodologies, including the principle of the assay, the transition from the initial bacteria inhibition test to the modern fluorometry test, and their respective advantages and disadvantages especially regarding specificity and sensitivity. Diagnosis can be confirmed by biochemical and/or molecular testing. Although newborn screening for classic galactosemia is highly successful, the high false-positive rate and long-term complications in treated galactosemia patients continue to pose some challenges. We are proposing a newborn screening follow-up testing algorithm to assist screening and differentiating four different forms of galactosemia including the most recently described galactosemia type IV. In the near future, we predict that liquid chromatography tandem mass spectrometry may become a new platform for galactosemia screening, due to its multiplexing capability. In-depth parallel sequencing may be integrated in newborn screening algorithm to confirm diagnoses and further reduce false-positive rate.

A novel missense mutation (c.516A>T; p.Glu172Asp) in the GALT gene as a cause of classic galactosemia: A case report

Classic galactosemia is an autosomal recessive disorder of galactose metabolism, which can result in life-threatening complications due to mutations within the GALT gene. Definite diagnosis of classic galactosemia is established by the detection of pathogenic mutations in the GALT gene. Herein we are reporting a novel missense mutation (c.516A>T; p.Glu172Asp) in exon 6 of the GALT gene in the homozygous state in a 2-year-old female infant. Screening-test for galactosemia was abnormal in this patient. We evaluated the GALT protein structure using molecular docking analysis. Accordingly, we identified that the Glu172 is one of the galactose 1-phosphate binding sites, and a substitution mutation in this position can disrupt the active site of GALT protein.

Current and Future Treatments for Classic Galactosemia.

Type I (classic) galactosemia, galactose 1-phosphate uridylyltransferase (GALT)-deficiency is a hereditary disorder of galactose metabolism. The current therapeutic standard of care, a galactose-restricted diet, is effective in treating neonatal complications but is inadequate in preventing burdensome complications. The development of several animal models of classic galactosemia that (partly) mimic the biochemical and clinical phenotypes and the resolution of the crystal structure of GALT have provided important insights; however, precise pathophysiology remains to be elucidated. Novel therapeutic approaches currently being explored focus on several of the pathogenic factors that have been described, aiming to (i) restore GALT activity, (ii) influence the cascade of events and (iii) address the clinical picture. This review attempts to provide an overview on the latest advancements in therapy approaches.

Gray and white matter are both affected in classical galactosemia: An explorative study on the association between neuroimaging and clinical outcome

BackgroundClassical Galactosemia (CG) is an inherited disorder of galactose metabolism caused by a deficiency of the galactose-1-phosphate uridylyltransferase (GALT) enzyme resulting in neurocognitive complications. As in many Inborn Errors of Metabolism, the metabolic pathway of CG is well-defined, but the pathophysiology and high variability in clinical outcome are poorly understood. The aim of this study was to investigate structural changes of the brain of CG patients on MRI and their association with clinical outcome. MethodsIn this prospective cohort study an MRI protocol was developed to evaluate gray matter (GM) and white matter (WM) volume of the cerebrum and cerebellum, WM hyperintensity volume, WM microstructure and myelin content with the use of conventional MRI techniques, diffusion tensor imaging (DTI) and quantitative T1 mapping. The association between several neuroimaging parameters and both neurological and intellectual outcome was investigated. ResultsTwenty-one patients with CG (median age 22 years, range 8–47) and 24 controls (median age 30, range 16–52) were included. Compared to controls, the WM of CG patients was lower in volume and the microstructure of WM was impaired both in the whole brain and corticospinal tract (CST) and the lower R1 values of WM, GM and the CST were indicative of less myelin. The volume of WM lesions were comparable between patients and controls. The 9/16 patients with a poor neurological outcome (defined as the presence of a tremor and/or dystonia), demonstrated a lower WM volume, an impaired WM microstructure and lower R1 values of the WM indicative of less myelin content compared to 7/16 patients without movement disorders. In 15/21 patients with a poor intellectual outcome (defined as an IQ < 85) both GM and WM were affected with a lower cerebral and cerebellar WM and GM volume compared to 6/21 patients with an IQ ≥ 85. Both the severity of the tremor (as indicated by the Tremor Rating Scale) and IQ (as continuous measure) were associated with several neuroimaging parameters such as GM volume, WM volume, CSF volume, WM microstructure parameters and R1 values of GM and WM. ConclusionIn this explorative study performed in patients with Classical Galactosemia, not only WM but also GM pathology was found, with more severe brain abnormalities on MRI in patients with a poor neurological and intellectual outcome. The finding that structural changes of the brain were associated with the severity of long-term complications indicates that quantitative MRI techniques could be of use to explain neurological and cognitive dysfunction as part of the disease spectrum. Based on the clinical outcome of patients, the absence of widespread WM lesions and the finding that both GM and WM are affected, CG could be primarily a GM disease with secondary damage to the WM as a result of neuronal degeneration. To investigate this further the course of GM and WM should be evaluated in longitudinal research, which could also clarify if CG is a neurodegenerative disease.

Classic galactosaemia in the Greek Cypriot population: An epidemiological and molecular study.

Classic galactosaemia is an inherited metabolic disorder of galactose metabolism caused by deficiency of the enzyme galactose‐1‐phosphate uridyltransferase (GALT) resulting from mutations in the GALT gene. The objectives of the present study were the determination of the carrier frequency of classic galactosaemia in the Greek Cypriot population and the molecular characterization of the disease alleles. We performed an epidemiological study involving 528 Greek Cypriots originating from all parts of Cyprus. Carriers were identified by measuring GALT activity in red blood cells and were subsequently subjected to mutation analysis. A total of five mutations were identified in patients and carriers of classic galactosaemia: a large deletion of 8.5 kb previously reported by us (55% of alleles), the known mutations p.Lys285Asn (30%), p.Pro185Ser (5%), and c.820+13A>G (5%), and a novel mutation c.378‐12G>A (5%). Interestingly, the most common mutation in European populations, p.Gln188Arg, was not identified in this Cypriot cohort. The carrier frequency for classic galactosaemia among Greek Cypriots was estimated to be 1:88, predicting a homozygote incidence of 1:31,000 births. The Duarte 1 and Duarte 2 variants were found to be present at a frequency of 5.5% and 2.5%, respectively.

Galactose-1-Phosphate Uridyltransferase Activities in Different Genotypes: A Retrospective Analysis of 927 Samples.

Classic galactosemia is an inherited disorder of galactose metabolism caused by the impaired activity of galactose-1-phosphate uridyltransferase (GALT). Untreated galactosemia is life-threatening; however, early dietary intervention prevents mortality and reduces morbidity associated with this disease. The diagnosis of galactosemia includes the measurement of GALT activity in red blood cells (RBC) and GALT gene analysis. In this study, we evaluate GALT activity in different genotypes using the results of combined biochemical and molecular testing in 927 samples. GALT activity in RBC was measured by LC-MS/MS. The analysis of the GALT gene was performed by targeted gene analysis and/or full gene sequencing. Samples were assigned based on the presence of pathogenic (G) or Duarte 2 (D) variants, or their absence (Neg), to G/G, D/G, G/Neg, D/D, D/Neg, and Neg/Neg genotypes. Finite mixture models were applied to investigate distributions of GALT activities in these genotypes. The reference ranges were determined using the central 95% of values of GALT activities. The ranges of GALT activity in G/G, D/G, G/Neg, D/D, D/Neg, and Neg/Neg genotypes are 0.0 to 0.7 μmol·h-1 gHb-1, 3.1 to 7.8 μmol·h-1 gHb-1, 6.5 to 16.2 μmol·h-1 gHb-1, 6.4 to 16.5 μmol·h-1 gHb-1, 12.0 to 24.0 μmol·h-1 gHb-1, and 19.4 to 33.4 μmol·h-1 gHb-1, respectively. The GALT activity ranges established in this study are in agreement with the expected impact of the genotype on the enzymatic activity. Molecular findings should be interpreted in view of biochemical results to confirm genotype-phenotype correlation.

Intrafamilial oocyte donation in classic galactosemia: ethical and societal aspects

Classic galactosemia is a rare inherited disorder of galactose metabolism. Primary ovarian insufficiency (POI) with subfertility affects > 80% of female patients and is an important concern for patients and their parents. Healthcare providers are often consulted for subfertility treatment possibilities. An option brought up by the families is intrafamilial oocyte donation (mother-to-daughter or sister-to-sister). In addition to POI, galactosemia patients can also present varying cognitive and neurological impairments, which may not be fully clear at the time when mother-to-daughter oocyte donation is considered. Ethical and societal aspects arise when exploring this option. This study aimed to provide guidance in aspects to consider based on the views of different groups involved in the oocyte donation process. A qualitative study using in-depth semi-structured interviews with > 50 participants (patients, family members, and healthcare providers) was conducted. From these interviews, themes of concern emerged, which are illustrated and reviewed: (1) family relations, (2) medical impact, (3) patients’ cognitive level, (4) agreements to be made in advance and organization of counseling, (5) disclosure to the child, and (6) need for follow-up. We conclude that discussing and carrying out intrafamilial oocyte donation in galactosemia patients requires carefully addressing these themes. This study adds value to the already existing recommendations on intrafamilial oocyte donation in general, since it highlights important additional aspects from the perspectives of patients and their families.

Spectrum of lysosomal disorders at a medical genetics center in the central part of the United States

Disclaimer: These ACMG Standards and Guidelines are developed primarily as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these Standards and Guidelines is voluntary and does not necessarily assure a successful medical outcome. These Standards and Guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the clinical laboratory geneticist should apply his or her own professional judgment to the specific circumstances presented by the individual patient or specimen. Clinical laboratory geneticists are encouraged to document in the patient’s record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these Standards and Guidelines. They also are advised to take notice of the date any particular guideline was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.Galactosemias are inherited disorders of galactose metabolism due to deficiency in one of the three enzymes involved in the Leloir pathway: galactose-1-phosphate uridyltransferase, galactokinase, and uridine diphosphate (UDP)-galactose-4′-epimerase. Galactose-1-phosphate uridyltransferase deficiency, or classic galactosemia, is the most frequent and the most severe of the three enzyme deficiencies; it is characterized by failure to thrive, liver failure, susceptibility to sepsis, and death, if untreated. Newborn screening for classic galactosemia has been implemented in all of the United States, while screening for galactokinase deficiency and UDP-galactose-4′-epimerase deficiency is not universal. Early identification and treatment of galactosemia leads to improved outcome. This document reviews the laboratory methods and best practices for the diagnosis of galactosemia.

Biochemical changes and clinical outcomes in 34 patients with classic galactosemia.

Impaired activity of galactose-1-phosphate uridyltransferase (GALT) causes galactosemia, an autosomal recessive disorder of galactose metabolism. Early initiation of a galactose-restricted diet can prevent or resolve neonatal complications. Despite therapy, patients often experience long-term complications including speech impairment, learning disabilities, and premature ovarian insufficiency in females. This study evaluates clinical outcomes in 34 galactosemia patients with markedly reduced GALT activity and compares outcomes between patients with different levels of mean galactose-1-phosphate in red blood cells (GAL1P) using logistic regression: group 1 (n = 13) GAL1P ≤1.7mg/dL vs. group 2 (n = 21) GAL1P ≥ 2mg/dL. Acute symptoms at birth were comparable between groups (p = 0.30) with approximately 50% of patients presenting with jaundice, liver failure, and failure-to-thrive. However, group 2 patients had significantly higher prevalence of negative long-term outcomes compared to group 1 patients (p = 0.01). Only one of 11 patients >3 yo in group 1 developed neurological and severe behavioral problems of unclear etiology. In contrast, 17 of 20 patients >3 yo in group 2 presented with one or more long-term complications associated with galactosemia. The majority of females ≥15 yo in this group also had impaired ovarian function with markedly reduced levels of anti-Müllerian hormone. These findings suggest that galactosemia patients with higher GAL1P levels are more likely to have negative long-term outcome. Therefore, evaluation of GAL1P levels on a galactose-restricted diet might be helpful in providing a prognosis for galactosemia patients with rare or novel genotypes whose clinical presentations are not well known.

Molecular basis and clinical presentation of classic galactosemia in a Croatian population.

Classic galactosemia is an autosomal recessive disorder of galactose metabolism caused by severely decreased activity of galactose-1-phosphate uridylyltransferase (GALT) due to pathogenic mutations in the GALT gene. To date more than 330 mutations have been described, with p.Q188R and p.K285N being the most common in Caucasian populations. Although acute manifestations can be fully avoided by a galactose-restricted diet, chronic complications, such as neurological ones, cannot be prevented in a significant number of patients despite compliance with the dietary treatment. A cohort of 16 galactosemic Croatian patients, including one pair of siblings, was studied. Molecular characterization was performed by direct sequence analysis of the GALT gene. Sixteen patients were analyzed and only four different mutations were detected. As expected, p.Q188R and p.K285N were common, accounting for 40% and 37% of unrelated alleles, respectively. The third mutation accounting for 20% of mutant alleles was p.R123X causing a premature stop codon, is thus considered to be severe, which is in accordance with the phenotype presented by the homozygous patient described here. The fourth mutation p.E271D was found in a single allele. More than half of our patients manifested some chronic neurological complications. This is the first report on mutational and phenotypic spectra of classic galactosemia in Croatia that expands the knowledge on the mutational map of the GALT gene across Europe and reveals the genetic homogeneity of the Croatian population.

Basic laboratory bone profile in Greek patients with galactose metabolic disorders

Basic laboratory bone profile in Greek patients with galactose metabolic disorders

Laboratory diagnosis of galactosemia: a technical standard and guideline of the American College of Medical Genetics and Genomics (ACMG).

Disclaimer: These ACMG Standards and Guidelines are developed primarily as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these Standards and Guidelines is voluntary and does not necessarily assure a successful medical outcome. These Standards and Guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the clinical laboratory geneticist should apply his or her own professional judgment to the specific circumstances presented by the individual patient or specimen. Clinical laboratory geneticists are encouraged to document in the patient's record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these Standards and Guidelines. They also are advised to take notice of the date any particular guideline was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.Galactosemias are inherited disorders of galactose metabolism due to deficiency in one of the three enzymes involved in the Leloir pathway: galactose-1-phosphate uridyltransferase, galactokinase, and uridine diphosphate (UDP)-galactose-4'-epimerase. Galactose-1-phosphate uridyltransferase deficiency, or classic galactosemia, is the most frequent and the most severe of the three enzyme deficiencies; it is characterized by failure to thrive, liver failure, susceptibility to sepsis, and death, if untreated. Newborn screening for classic galactosemia has been implemented in all of the United States, while screening for galactokinase deficiency and UDP-galactose-4'-epimerase deficiency is not universal. Early identification and treatment of galactosemia leads to improved outcome. This document reviews the laboratory methods and best practices for the diagnosis of galactosemia.

Impaired fertility and motor function in a zebrafish model for classic galactosemia

Classic galactosemia is a genetic disorder of galactose metabolism, caused by severe deficiency of galactose-1-phosphate uridylyltransferase (GALT) enzyme activity due to mutations of the GALT gene. Its pathogenesis is still not fully elucidated, and a therapy that prevents chronic impairments is lacking. In order to move research forward, there is a high need for a novel animal model, which allows organ studies throughout development and high-throughput screening of pharmacologic compounds. Here, we describe the generation of a galt knockout zebrafish model and present its phenotypical characterization. Using a TALEN approach, a galt knockout line was successfully created. Accordingly, biochemical assays confirm essentially undetectable galt enzyme activity in homozygotes. Analogous to humans, galt knockout fish accumulate galactose-1-phosphate upon exposure to exogenous galactose. Furthermore, without prior exposure to exogenous galactose, they exhibit reduced motor activity and impaired fertility (lower egg quantity per mating, higher number of unsuccessful crossings), resembling the human phenotype(s) of neurological sequelae and subfertility. In conclusion, our galt knockout zebrafish model for classic galactosemia mimics the human phenotype(s) at biochemical and clinical levels. Future studies in our model will contribute to improved understanding and management of this disorder.

Galactose‐1‐phosphate uridyltransferase deficiency: A literature review of the putative mechanisms of short and long‐term complications and allelic variants

Galactosemia type 1 is an autosomal recessive disorder of galactose metabolism, determined by a deficiency in the enzyme galactose-1-phosphate uridyltransferase (GALT). GALT deficiency is classified as severe or variant depending on biochemical phenotype, genotype and potential to develop acute and long-term complications. Neonatal symptoms usually resolve after galactose-restricted diet; however, some patients, despite the diet, can develop long-term complications, in particular when the GALT enzyme activity results absent or severely decreased. The mechanisms of acute and long-term complications are still discussed and several hypotheses are presented in the literature like enzymatic inhibition, osmotic stress, endoplasmic reticulum stress, oxidative stress, defects of glycosylation or epigenetic modification. This review summarizes the current knowledge of galactosemia, in particular the putative mechanisms of neonatal and long-term complications and the molecular genetics of GALT deficiency.

Classical galactosemia in a Thai infant: case report and review of the literature

Abstract Background Classic galactosemia is an inherited disorder of galactose metabolism that is caused by a deficiency of galactose-1-phosphate uridyl transferase (GALT). As in other Asians, the prevalence of galactosemia in Thai people is very low. An accumulation of its toxic metabolites leads to acute neonatal toxicity and long-term complications. Objective To present the fourth known published case of classical galactosemia in a Thai infant and review the English language literature. Method A 4-month-old boy who was born into a Thai family with no history of consanguinity developed persistent jaundice, hepatosplenomegaly, and lethargy, since introduction to breast-feeding. Result Urine gas chromatography-mass spectrometry demonstrated a high level of galactose, galactitol, and galactonate. Liver biopsy confirmed severe hepatocellular damage and fibrosis. Breast-feeding was immediately replaced by a lactose-free diet and soy milk. His clinical features and subsequent laboratory measurements improved. Developmental delays and defects on speech presented at the last followed up. Conclusion Long-term complications are diet-independent and inevitable. However early recognition and immediate withdraw of galactose from the diet can prevent serious morbidity and mortality.