"Galactosemia"

Govorestat for treating galactosemia in people aged 2-65 years Govorestat for treating galactosemia in people aged 2-65 years - NIHR Innovation Observatory * Who we are * What we do * Our Networks * Engage * Events * News * Resources Get in touch * * A world leading Horizon Scanning Facility The NIHR Innovation Observatory is a world leading health and care innovation scanning centre, providing * Imminent horizon * Our Networks * Our Stakeholders * Our Work with NICE * Health & Life Sciences Ecosystem * Engage * Industry * Public Involvement * Capacity Building * Events * News * Resources * Contact 25 June 2024 Govorestat for treating galactosemia in people aged 2-65 yearsGovorestat is in clinical development for treating classic galactosemia. Classic galactosemia is a rare disorder affecting

A case report of classic galactosemia with a GALT gene variant and a literature review. Galactosemia is an autosomal recessive disorder resulting from an enzyme defect in the galactose metabolic pathway. The most severe manifestation of classic galactosemia is caused by galactose-1-phosphate uridylyltransferase (GALT) deficiency, and this condition can be fatal during infancy if left untreated contribute to the development of classical galactosemia. Applications of whole-exome sequencing to detect the two variants can improve the detection and early diagnosis of classical galactosemia and, more specifically, may identify individuals who are compound heterozygous with variants in the GALT gene. Variants in the GALT gene have a potential therapeutic significance for classical galactosemia.

Sepsis caused by Phytobacter diazotrophicus complicated with galactosemia type 1 in China: a case report. Phytobacter diazotrophicus (P. diazotrophicus) is an opportunistic pathogen that causes nosocomial outbreaks and sepsis. However, there are no reports of P. diazotrophicus isolated from human blood in China. A 27-day-old female infant was admitted to our hospital with fever and high bilirubin levels. The clinical features included jaundice, abnormal coagulation, cholestasis, fever, convulsions, weak muscle tension, sucking weakness, ascites, abnormal tyrosine metabolism, cerebral oedema, abnormal liver function, clavicle fracture, and haemolytic anaemia. The strain isolated from the patient's blood was identified as P. diazotrophicus by whole-genome sequencing (WGS). Galactosemia

Clinical and biochemical evolution after partial dietary liberalization of two cases of galactosemia due to galactose mutarotase deficiency. The recommended diet attitude in the recently described galactose mutarotase (GALM) deficiency is not yet established. We describe two 9-years twins who remain asymptomatic despite prolonged partial dietary liberalization from 18 months of age, after two periods of galactose-free diet. It represents the second report in Europe of GALM deficiency. Two male monochorionic diamniotic twins were detected through newborn screening by galactosuria and increased total blood galactose. They started galactose dietary restriction with biochemical normalization. After exclusion of the three previously described types of galactosemia, a progressively galactose

Feasibility of a Proactive Parent-Implemented Communication Intervention Delivered via Telepractice for Children With Classic Galactosemia. This study evaluated the feasibility of Babble Boot Camp (BBC) for use with infants with classic galactosemia (CG) starting at less than 6 months of age. BBC is a parent-implemented intervention delivered by speech-language pathologists (SLPs) entirely via

Translating principles of precision medicine into speech-language pathology: Clinical trial of a proactive speech and language intervention for infants with classic galactosemia. Precision medicine is an emerging approach to managing disease by taking into consideration an individual's genetic and environmental profile toward two avenues to improved outcomes: prevention and personalized and language disorders in infants at predictable risk by fostering precursor and early communication skills via parent training. The intervention begins at child age 2 to 5 months and ends at age 24 months, with follow-up testing at 30, 42, and 54 months. To date, 44 children with a newborn diagnosis of classic galactosemia (CG) have participated in the clinical trial of BBC. CG is an inborn error

The hypergonadotropic hypogonadism conundrum of classic galactosemia. Hypergonadotropic hypogonadism is a burdensome complication of classic galactosemia (CG), an inborn error of galactose metabolism that invariably affects female patients. Since its recognition in 1979, data have become available regarding the clinical spectrum, and the impact on fertility. Many women have been counseled using the following terms: 'classic galactosemia', 'gonadal damage', 'primary ovarian insufficiency', 'fertility', 'animal models' and 'fertility preservation' in combination with other keywords related to the subject area. All relevant publications until August 2022 have been critically evaluated and reviewed. A diagnosis of premature ovarian insufficiency (POI) results in a significant psychological

Laparoscopic ovarian tissue harvesting for cryopreservation from a child with galactosemia. To describe an approach to fertility preservation by a multidisciplinary team of reproductive endocrinology and infertility, pediatric gynecology and surgery, and genetics experts via ovarian tissue harvesting and cryopreservation for a toddler with galactosemia. Galactosemia is associated with progressive primary ovarian insufficiency (POI) and early intervention with ovarian tissue cryopreservation may help preserve fertility. Video description of a tissue harvesting and cryopreservation technique. Academic institution. 16-month-old female with classic galactosemia. At 6 months of age, despite good metabolic control, the infant's antimüllerian hormone (AMH) level was <0.015 ng/ml; luteinizing

Newborn blood spot screening for galactosemia, tyrosiemia type I, homocystinuria, sickle cell anemia, sickle cell/beta-thalassemia, sickle cell/hemoglobin C disease and severe combined immunodeficiency Newborn blood spot screening for galactosemia, tyrosiemia type I, homocystinuria, sickle cell anemia, sickle cell/beta-thalassemia, sickle cell/hemoglobin C disease and severe combined ..

Novel mRNA-Based Therapy Reduces Toxic Galactose Metabolites and Overcomes Galactose Sensitivity in a Mouse Model of Classic Galactosemia. Classic galactosemia (CG) is a potentially lethal inborn error of galactose metabolism that results from deleterious mutations in the human galactose-1 phosphate uridylyltransferase (GALT) gene. Previously, we constructed a GalT (GalT-deficient) mouse model

Biallelic GALM pathogenic variants cause a novel type of galactosemia. Galactosemia is caused by metabolic disturbances at various stages of galactose metabolism, including deficiencies in enzymes involved in the Leloir pathway (GALT, GALK1, and GALE). Nevertheless, the etiology of galactosemia has not been identified in a subset of patients. This study aimed to explore the causes of unexplained galactosemia. Trio-based exome sequencing and/or Sanger sequencing was performed in eight patients with unexplained congenital galactosemia. In vitro enzymatic assays and immunoblot assays were performed to confirm the pathogenicity of the variants. The highest blood galactose levels observed in each patient were 17.3-41.9 mg/dl. Bilateral cataracts were observed in two patients. In all eight patients, we

Toward a paradigm shift from deficit-based to proactive speech and language treatment: Randomized pilot trial of the Babble Boot Camp in infants with classic galactosemia. Speech and language therapy is typically initiated reactively after a child shows delays. Infants with classic galactosemia (CG), a metabolic disease with a known high risk for both speech and language disorders, hold

Extreme neonatal hyperbilirubinemia, acute bilirubin encephalopathy, and kernicterus spectrum disorder in children with galactosemia. Galactosemia has not been recognized as a cause of extreme neonatal hyperbilirubinemia, although growing evidence supports this association. In a retrospective cohort study, we identified children with galactosemia due to GALT deficiency using the Danish Metabolic Laboratory Database. Among these, we identified children with extreme neonatal hyperbilirubinemia or symptoms of ABE. Extreme neonatal hyperbilirubinemia was defined as maximum total serum bilirubin (TSB) level ≥450 µmol/L and a ratio of conjugated serum bilirubin/TSB <0.30. We identified 21 children with galactosemia (incidence:1:48,000). Seven children developed extreme neonatal hyperbilirubinemia

Arginine does not rescue p.Q188R mutation deleterious effect in classic galactosemia Classic galactosemia is a rare genetic metabolic disease with an unmet treatment need. Current standard of care fails to prevent chronically-debilitating brain and gonadal complications. Many mutations in the GALT gene responsible for classic galactosemia have been described to give rise to variants with conformational abnormalities. This pathogenic mechanism is highly amenable to a therapeutic strategy based on chemical/pharmacological chaperones. Arginine, a chemical chaperone, has shown beneficial effect in other inherited metabolic disorders, as well as in a prokaryotic model of classic galactosemia. The p.Q188R mutation presents a high prevalence in the Caucasian population, making it a very clinically

Profiling of intracellular metabolites produced from galactose and its potential for galactosemia research Clinical outcome of patients with a classical presentation of galactosemia (classical patients) varies substantially, even between patients with the same genotype. With current biomarkers, it is not possible to predict clinical outcome early in life. The aim of this study was to develop a method to provide more insight into galactose metabolism, which allows quantitative assessment of residual galactose metabolism in galactosemia patients. We therefore developed a method for galactose metabolite profiling (GMP) in fibroblasts using [U-C]-labeled galactose. GMP analysis was performed in fibroblasts of three classical patients, three variant patients and three healthy controls

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

Pilot study of classic galactosemia: Neurodevelopmental impact and other complications urge neonatal screening in Egypt Classic galactosemia is caused by deficiency of galactose-1-phosphate uridylyltransferase (GALT). It causes serious morbidity and mortality if left untreated. Screening for galactosemia is not included in Egyptian neonatal screening program. The study aimed to define clinical presentation and complications of galactosemia at Pediatric Hepatology Clinic, Cairo University, Egypt. Thus, the clinical presentation, course and outcome of 37 children with documented galactosemia was studied. Jaundice was the main presentation (67.6%). Other presentations included; convulsions (29.7%), motor retardation (24.3%), mental retardation (5.4%), microcephaly (5.4%), failure to thrive (16.2

Developmental Outcomes in Duarte Galactosemia. : media-1vid110.1542/5849572227001PEDS-VA_2018-2516 OBJECTIVES: For decades, infants with Duarte galactosemia (DG) have been identified by newborn screening (NBS), but whether they should be treated with dietary restrictions of galactose has remained unknown. To clarify, we conducted a study of dietary and developmental outcomes in 206 children

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 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

Fertility in adult women with classic galactosemia and primary ovarian insufficiency. To study pregnancy chance in adult women with classic galactosemia and primary ovarian insufficiency. Despite dietary treatment, >90% of women with classic galactosemia develop primary ovarian insufficiency, resulting in impaired fertility. For many years, chance of spontaneous conception has not been considered, leading to counseling for infertility. But an increasing number of reports on pregnancies in this group questions whether current counseling approaches are correct. Multicenter retrospective observational study. Metabolic centers. Adult women (aged >18 y) with confirmed classic galactosemia and primary ovarian insufficiency were included. Participants and medical records were consulted