RARE DISEASE
Galactosemia
Galactosemia
Galactosemia
Drug discovery
2
drugs
With orphan designations
Overview
Galactosemia is an autosomal recessive disorder of galactose metabolism caused by deficient activity of enzymes (GALT, GALK1, or GALE) in the Leloir pathway [1][6]. Classic galactosemia (GALT deficiency) presents with acute neonatal toxicity (jaundice, failure to thrive, sepsis) without dietary restriction and chronic complications including intellectual disability, speech deficits, premature ovarian insufficiency, and movement disorders despite lifelong lactose/galactose avoidance [1][4][5]. While newborn screening enables early diagnosis, endogenous galactose production perpetuates disease progression [8][16].
Categories: rare genetic diseases, rare inborn errors of metabolism, rare ophthalmic disorders, rare renal diseases
Research Papers
470 drug discovery papers about Galactosemia, with 3 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
470 drug discovery papers about Galactosemia, with 3 first-in-class and 3 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-01 | Reproductive potential in classical galactosemia: A case series based perspective.
Classical galactosemia (CG), caused by galactose-1-phosphate uridylyltransferase (GALT) enzyme deficiency, is associated with premature ovarian insufficiency (POI) and subfertility. The last years, a counseling paradigm shift has been advocated with emphasis on subfertility instead of infertility because spontaneous pregnancy can occur. We describe two women (aged 26 and 30 years) with genetically confirmed CG and POI, who conceived spontaneously. Both adhered to lifelong galactose-restricted diet and had regular endocrine monitoring. Their pregnancies were uncomplicated and each delivered a healthy infant at term. These cases are in line with the counseling paradigm shift, with natural conception being possible in CG. Reproductive counselling of girls and women with CG should entail fertility preservation and spontaneous pregnancy. In case of desired pregnancy, a period of two years to attempt conceiving should be advised. AMH is not a reliable prognostic parameter for predicting the reproductive potential in CG.
2026-05-17 | Decompensated cirrhosis in an adult revealing probable congenital galactosemia: A case report
Congenital galactosemia is an autosomal recessive inborn error of metabolism, most commonly caused by a deficiency of galactose-1-phosphate uridyltransferase (GALT). It typically presents during the neonatal period with acute liver failure, cataracts, and neurological impairment. Diagnosis in adulthood is exceptional. We report the case of a 30-year-old woman admitted for upper gastrointestinal bleeding revealing cirrhosis with portal hypertension. Medical history included bilateral cataract surgery performed twice, psychomotor delay, bilateral hearing impairment, and a history of unexplored neonatal jaundice. A comprehensive etiological workup for chronic liver disease was negative. Plasma galactose level was elevated at 1.2 mg/dL (normal < 0.7 mg/dL). In the absence of enzymatic and genetic confirmation due to socioeconomic constraints, the diagnosis of probable congenital galactosemia was retained based on a consistent set of clinical and biological findings. This case highlights the rare possibility of late presentation in adulthood and emphasizes the importance of considering a metabolic etiology in unexplained cirrhosis associated with suggestive systemic manifestations.
2026-03-20 | Hepatic and Extra-hepatic Outcomes of Classical Galactosemia in Infants: A Longitudinal Observational Study.
Classical galactosemia (CG), if untreated, can be life threatening in early infancy; however, with early galactose restriction, survival has improved markedly. Despite early diagnosis and dietary exclusion, complications may ensue. This study aimed to identify risk factors for adverse outcomes in CG. We conducted an analysis of our prospectively maintained database. Diagnosis was based on galactose-1-phosphate uridyltransferase (GALT) enzyme levels <10u/gm hemoglobin or mutation of the GALT gene. Clinical and laboratory data were retrieved from hospital electronic records and analyzed to identify potential predictors of mortality or neuro-ophthalmic morbidity (poor neurocognition, learning disability, and new-onset or persistent cataract). Fifty-nine CG patients presented with infantile cholestasis. Their median age of symptom onset and diagnosis was 16 (interquartile range [IQR]: 3-90) and 50 (IQR: 4-120) days, respectively. Among the 48 survivors, 41 had follow-up for ≥18 months and were analyzed for long-term outcomes. Complete liver recovery was documented in all 41 patients, with a median time to recovery of 5 months (IQR: 3-8) following diagnosis. On a lactose-free diet (LFD), 8 (19.5%) developed new-onset cataracts, and 21 (51.2%) patients had neurocognitive issues. The univariate analysis of non-survivors (n = 11) versus survivors (n = 48) identified risk factors: older age at diagnosis, high baseline Child-Turcotte-Pugh (CTP) and Pediatric End-Stage Liver Disease (PELD) scores, low serum sodium and albumin levels, and higher international normalized ratio values. In addition, refractory ascites, persistent coagulopathy at 4 weeks on LFD, and culture-positive sepsis were significantly associated risk factors in the non-survival group. No significant predictors were found for neurocognitive issues and cataract in follow-up. PELD and CTP scores at admission predict survival. Long-term neuro-ophthalmic morbidity is not associated with liver disease severity at onset in CG.
2026-03-09 | Galactose tolerance in adults with classical galactosaemia. Considering the gaps.
Classical galactosaemia (CG, OMIM 230400) is a rare inborn error of metabolism caused by deficiency of galactose-1-phosphate uridylyltransferase. The available modality of treatment, a galactose-restricted diet, is effective in preventing life-threatening neonatal symptoms. However long-term complications including neurological, speech and fertility issues in females remain prevalent. This retrospective review reports the experience of mild-moderate relaxation of dietary galactose intake over time in a cohort of 31 Irish CG adult patients with established RBC Gal-1-P, and novel IgG N-glycan analysis. Three groups were categorised based on the retrospective analysis of estimated dietary galactose intake: Group 1 (<200 mg/day), Group 2 (200-500 mg/day) and Group 3 (501-1000 mg/day). Dietary galactose intake was compared to matching RBC Gal-1-P levels and serum IgG N-glycan profiles (measured by HILIC-UPLC). RBC Gal-1-P levels increased with increased galactose intake with statistically significant differences only between the lowest and highest galactose intake group (p < 0.05). Minor changes were seen in a number of IgG N-glycans in the highest galactose intake group with increases in core fucosylated monoantennary and biantennary monogalactosylated monosialylated glycans, pentamannosylated glycans, oligomannosylated glycans and monoantennary glycans with a decrease in grouped biantennary glycans. The most significant change noted was an increase in pentamannosylated glycans with increased dietary galactose intake. Moderate relaxation of dietary galactose intake (up to 500 mg/day) may be well tolerated in the majority of CG adults. These data suggest that serum N-glycan profiling may provide an improved individualised 'personalised medicine' approach for treatment interventions for CG, considering individualised variation in glycosylation, including 'glycosylation outliers'.
2025-11-21 | Experimental Galactose-1-Phosphate Uridylyltransferase (GALT) mRNA Therapy Improves Motor-Related Phenotypes in a Mouse Model of Classic Galactosemia—A Pilot Study
Background: Despite life-saving newborn screening programs and a life-long galactose-restricted diet, many patients with classic galactosemia continue to develop long-term debilitating neurological deficits, speech dyspraxia, and primary ovarian insufficiency (POI). In an earlier study, we showed that administration of an experimental human GALT mRNA predominantly expressed in the liver of the GalT gene-trapped mouse model augmented the expression of hepatic GALT activity, which reduced build-up of galactose and its toxic metabolites not only in the liver but also in the peripheral tissues. Moreover, we showed that the administration of GALT mRNA in the mutant mice restored whole-body galactose oxidation (WBGO), which is a functional biomarker. Methods: In this pilot study, we extended our proof-of-concept efficacy studies to a disease-relevant phenotype: motor impairment. GalT-KO mice aged 3 and 6 weeks old administered biweekly intravenous injections of 100 µL GALT mRNA at a dose of 2 mg/kg for 2 months. Motor performance was assessed using rotarod testing and composite phenotype scoring, 3 and 9 weeks following the dosing regimen. Results: Preliminary results showed that a biweekly dosing at 2 mg/kg for 2 months improved the motor performance of the animals in rotarod and composite phenotype scoring tests in a short-term experiment. Conclusions: Despite being a small-scale study, our findings suggest that when treated early in life, the experimental GALT mRNA is effective in improving the motor-related phenotypes in GalT-KO mice using the specified dosing regimen. These findings highlight the potential of mRNA-based therapies for mitigating neurological symptoms in Classic galactosemia.
2026-07-01 | Reproductive potential in classical galactosemia: A case series based perspective.
Classical galactosemia (CG), caused by galactose-1-phosphate uridylyltransferase (GALT) enzyme deficiency, is associated with premature ovarian insufficiency (POI) and subfertility. The last years, a counseling paradigm shift has been advocated with emphasis on subfertility instead of infertility because spontaneous pregnancy can occur. We describe two women (aged 26 and 30 years) with genetically confirmed CG and POI, who conceived spontaneously. Both adhered to lifelong galactose-restricted diet and had regular endocrine monitoring. Their pregnancies were uncomplicated and each delivered a healthy infant at term. These cases are in line with the counseling paradigm shift, with natural conception being possible in CG. Reproductive counselling of girls and women with CG should entail fertility preservation and spontaneous pregnancy. In case of desired pregnancy, a period of two years to attempt conceiving should be advised. AMH is not a reliable prognostic parameter for predicting the reproductive potential in CG.
2026-05-17 | Decompensated cirrhosis in an adult revealing probable congenital galactosemia: A case report
Congenital galactosemia is an autosomal recessive inborn error of metabolism, most commonly caused by a deficiency of galactose-1-phosphate uridyltransferase (GALT). It typically presents during the neonatal period with acute liver failure, cataracts, and neurological impairment. Diagnosis in adulthood is exceptional. We report the case of a 30-year-old woman admitted for upper gastrointestinal bleeding revealing cirrhosis with portal hypertension. Medical history included bilateral cataract surgery performed twice, psychomotor delay, bilateral hearing impairment, and a history of unexplored neonatal jaundice. A comprehensive etiological workup for chronic liver disease was negative. Plasma galactose level was elevated at 1.2 mg/dL (normal < 0.7 mg/dL). In the absence of enzymatic and genetic confirmation due to socioeconomic constraints, the diagnosis of probable congenital galactosemia was retained based on a consistent set of clinical and biological findings. This case highlights the rare possibility of late presentation in adulthood and emphasizes the importance of considering a metabolic etiology in unexplained cirrhosis associated with suggestive systemic manifestations.
2026-03-20 | Hepatic and Extra-hepatic Outcomes of Classical Galactosemia in Infants: A Longitudinal Observational Study.
Classical galactosemia (CG), if untreated, can be life threatening in early infancy; however, with early galactose restriction, survival has improved markedly. Despite early diagnosis and dietary exclusion, complications may ensue. This study aimed to identify risk factors for adverse outcomes in CG. We conducted an analysis of our prospectively maintained database. Diagnosis was based on galactose-1-phosphate uridyltransferase (GALT) enzyme levels <10u/gm hemoglobin or mutation of the GALT gene. Clinical and laboratory data were retrieved from hospital electronic records and analyzed to identify potential predictors of mortality or neuro-ophthalmic morbidity (poor neurocognition, learning disability, and new-onset or persistent cataract). Fifty-nine CG patients presented with infantile cholestasis. Their median age of symptom onset and diagnosis was 16 (interquartile range [IQR]: 3-90) and 50 (IQR: 4-120) days, respectively. Among the 48 survivors, 41 had follow-up for ≥18 months and were analyzed for long-term outcomes. Complete liver recovery was documented in all 41 patients, with a median time to recovery of 5 months (IQR: 3-8) following diagnosis. On a lactose-free diet (LFD), 8 (19.5%) developed new-onset cataracts, and 21 (51.2%) patients had neurocognitive issues. The univariate analysis of non-survivors (n = 11) versus survivors (n = 48) identified risk factors: older age at diagnosis, high baseline Child-Turcotte-Pugh (CTP) and Pediatric End-Stage Liver Disease (PELD) scores, low serum sodium and albumin levels, and higher international normalized ratio values. In addition, refractory ascites, persistent coagulopathy at 4 weeks on LFD, and culture-positive sepsis were significantly associated risk factors in the non-survival group. No significant predictors were found for neurocognitive issues and cataract in follow-up. PELD and CTP scores at admission predict survival. Long-term neuro-ophthalmic morbidity is not associated with liver disease severity at onset in CG.
2026-03-09 | Galactose tolerance in adults with classical galactosaemia. Considering the gaps.
Classical galactosaemia (CG, OMIM 230400) is a rare inborn error of metabolism caused by deficiency of galactose-1-phosphate uridylyltransferase. The available modality of treatment, a galactose-restricted diet, is effective in preventing life-threatening neonatal symptoms. However long-term complications including neurological, speech and fertility issues in females remain prevalent. This retrospective review reports the experience of mild-moderate relaxation of dietary galactose intake over time in a cohort of 31 Irish CG adult patients with established RBC Gal-1-P, and novel IgG N-glycan analysis. Three groups were categorised based on the retrospective analysis of estimated dietary galactose intake: Group 1 (<200 mg/day), Group 2 (200-500 mg/day) and Group 3 (501-1000 mg/day). Dietary galactose intake was compared to matching RBC Gal-1-P levels and serum IgG N-glycan profiles (measured by HILIC-UPLC). RBC Gal-1-P levels increased with increased galactose intake with statistically significant differences only between the lowest and highest galactose intake group (p < 0.05). Minor changes were seen in a number of IgG N-glycans in the highest galactose intake group with increases in core fucosylated monoantennary and biantennary monogalactosylated monosialylated glycans, pentamannosylated glycans, oligomannosylated glycans and monoantennary glycans with a decrease in grouped biantennary glycans. The most significant change noted was an increase in pentamannosylated glycans with increased dietary galactose intake. Moderate relaxation of dietary galactose intake (up to 500 mg/day) may be well tolerated in the majority of CG adults. These data suggest that serum N-glycan profiling may provide an improved individualised 'personalised medicine' approach for treatment interventions for CG, considering individualised variation in glycosylation, including 'glycosylation outliers'.
2025-11-21 | Experimental Galactose-1-Phosphate Uridylyltransferase (GALT) mRNA Therapy Improves Motor-Related Phenotypes in a Mouse Model of Classic Galactosemia—A Pilot Study
Background: Despite life-saving newborn screening programs and a life-long galactose-restricted diet, many patients with classic galactosemia continue to develop long-term debilitating neurological deficits, speech dyspraxia, and primary ovarian insufficiency (POI). In an earlier study, we showed that administration of an experimental human GALT mRNA predominantly expressed in the liver of the GalT gene-trapped mouse model augmented the expression of hepatic GALT activity, which reduced build-up of galactose and its toxic metabolites not only in the liver but also in the peripheral tissues. Moreover, we showed that the administration of GALT mRNA in the mutant mice restored whole-body galactose oxidation (WBGO), which is a functional biomarker. Methods: In this pilot study, we extended our proof-of-concept efficacy studies to a disease-relevant phenotype: motor impairment. GalT-KO mice aged 3 and 6 weeks old administered biweekly intravenous injections of 100 µL GALT mRNA at a dose of 2 mg/kg for 2 months. Motor performance was assessed using rotarod testing and composite phenotype scoring, 3 and 9 weeks following the dosing regimen. Results: Preliminary results showed that a biweekly dosing at 2 mg/kg for 2 months improved the motor performance of the animals in rotarod and composite phenotype scoring tests in a short-term experiment. Conclusions: Despite being a small-scale study, our findings suggest that when treated early in life, the experimental GALT mRNA is effective in improving the motor-related phenotypes in GalT-KO mice using the specified dosing regimen. These findings highlight the potential of mRNA-based therapies for mitigating neurological symptoms in Classic galactosemia.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
2 orphan drug designations for Galactosemia.
2 orphan drug designations for Galactosemia.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Adeno-associated virus 2/9 expressing human GALT gene (AAV2/9-hGALT) | gene therapies | FDA | 2021-09-28 | — | Jaguar Gene Therapy, LLC |
2-(4-oxo-3-((5-(trifluoromethyl)benzo[d]thiazol-2-yl)methyl)-3,4-dihydrothieno[3,4-d]pyridazin-1-yl)acetic acid | small molecules | FDA | 2019-05-23 | — | Applied Therapeutics Inc. |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.