Maple Syrup Urine Research Articles (Page 1)

Superoxide anion production and mitochondrial dysfunction in Maple Syrup Urine Disease: An ex vivo study on human neonate skin fibroblast cultures.

Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by mutations in the BCKDHA, BCKDHB, DBT, and DLD genes, which encode subunits of the branched-chain α-keto acid dehydrogenase complex. Understanding the genetic basis of MSUD is essential for accurate diagnosis, genetic counseling, and therapeutic interventions. This study aimed to characterize mutations in the BCKDHA, BCKDHB, DBT, and DLD genes among Azerbaijani patients clinically diagnosed with MSUD. Between 2015 and 2020, blood samples were collected from 940 individuals representing various regions of Azerbaijan. Exome and Sanger sequencing were employed to detect variants in the four target genes, with Sanger sequencing used to validate exome-identified variants in BCKDHB and DBT. Structural modeling of mutant proteins was conducted using the SWISS-MODEL platform to predict the functional impact of the mutations. Four novel missense mutations were identified in three unrelated patients from the Guba–Khachmaz region: c.1221A>G, c.972C>T, and c.508C>T in the BCKDHB gene, and c.1199A>G in the DBT gene. All variants were predicted to be pathogenic and associated with amino acid substitutions that potentially disrupt protein conformation. Notably, one patient belonged to the Azerbaijani Turk ethnic group, and two were from the Lezgi community. This study reports, for the first time, novel pathogenic mutations in Azerbaijani MSUD patients, expanding the mutational spectrum of BCKDHB and DBT genes. The findings highlight the importance of ethnically tailored genetic screening and provide valuable data for molecular diagnosis, carrier detection, and the development of personalized management strategies for MSUD in Azerbaijan.

Disclosure: B. Zaidan: None. M. Pennant: None.Background: Maple Syrup Urine Disease (MSUD) is an autosomal recessive disorder caused by a defect in the branched-chain alpha-ketoacid dehydrogenase (BCKAD) complex, essential for metabolizing branched-chain amino acids (BCAAs): isoleucine, leucine, and valine. These amino acids are crucial for cellular signaling, cholesterol synthesis, energy production, and mTOR pathway regulation. Leucine activates mTORC1, affecting insulin sensitivity (1). Excessive BCAA intake can elevate mTORC1 activity, leading to insulin resistance and type 2 diabetes (2,3). Case-control studies link BCAA metabolism to insulin resistance and diabetes risk (4). Though HbA1c data in MSUD adults is limited, a case report describes a 4-year-old with MSUD and type 1 diabetes, managed with dietary changes and insulin (2,3). Case description: A 40-year-old male with a medical history of maple syrup urine disease (MSUD), anxiety, and prediabetes has experienced multiple hospitalizations due to MSUD crises. His most recent admission was complicated by acute leucine encephalopathy, raising concerns about the progression to type 2 diabetes mellitus (T2DM). The underlying triggers for these metabolic crises have often been unclear. During hospitalization, the patient adhered to a strict dietary regimen, limiting protein intake to a maximum of 45 grams per day. He was maintained on MSUD-specific formulas, such as Ketonex, designed to provide essential nutrients while minimizing leucine, isoleucine, and valine intake. His glucose intolerance was closely monitored even before the T2DM diagnosis through HbA1C and blood glucose measurements. Over the years, his HbA1C levels varied, 5.4%, 6.5%, and most recently 5.6%. While his early glucose values were within the normal range, prior to and around the time of T2DM diagnosis, a higher reading with an average of 126 mg/dL, with the highest of 418 mg/dL and a lowest of 72 mg/dL (normal range: 74-109 mg/dL). What made this case unique was the challenge of managing his impaired glucose tolerance without worsening MSUD. Individuals with MSUD require pure starch and simple sugars to maintain balanced branched-chain amino acids (BCAA) levels. During this hospitalization, we adopted a dietary strategy that maintained adequate simple carbohydrate intake while continuing Ketonex supplementation. Conclusion: This case underscores the necessity of timely and appropriate management in patients with MSUD to prevent severe complications. A multidisciplinary treatment approach is crucial to navigate the intricacies of the disease, dietary adherence, and psychological health. Future efforts should focus on improving care coordination and patient education to enhance the quality of life for individuals with this complex condition.Presentation: Monday, July 14, 2025

Abstract Background Inborn errors of metabolism (IEM) are a phenotypically and genetically variable group of diseases produced by a variety of disorders in the metabolic pathway. They are more common in countries with a high consanguinity rate, such as Egypt. This study aimed to explore the frequency of IEM among eighty children who attend the Metabolic Outpatient Clinic at Alexandria University Children’s Hospital (AUCH) for follow-up from September 2019 to February 2023. Those children has been diagnosed clinically, radiologically and biochemically by using extended metabolic screening including amino acid screen, urine organic acids measurement and tandem mass spectrometry (TMS). Data about age, sex, birth order, area of residence, age at onset, presenting complaints, and family history of the same disease were all collected from caregivers and hospital records. Results There was a male predominance of 46 cases (57.5%), and females accounted for 34 (42.5%). Twenty percent of the studied cases had a history of a similar condition in their family. Specifically, 21 cases (26.3%) had maple syrup urine disease (MSUD), 19 cases (23.8%) had glutaric acidemia (GA) type 1, 13 cases (16.3%) had methylmalonic acidemia (MMA), and 8 (10%) had isovaleric acidemia (IVA). Only 2 cases (2.5%) of the studied cases had fatty acid oxidation defects (FAOD), and there was only one case (1.3%) of 3-hydroxy-3-methylglutaryl-CoA lyase deficiency (HMG-CoA) and one cases (1.3%) of propionic acidemia (PA). Conclusion IEM are frequent among children, and further research studies are needed to gain a better understanding of their nature, highlighting the importance of neonatal screening and timely diagnosis to improve outcomes of affected children. As prevalence of some disorders seem to be more common, it is better to address on newborn screening program (NBS) to address them.

Background: Maple syrup urine disease (MSUD) is a genetic disorder caused by mutations in the branched-chain α-ketoacid dehydrogenase (BCKDH) complex, leading to toxic buildup of branched-chain amino acids (BCAAs) and their ketoacid derivatives. While newborn screening (NBS) and molecular testing are standard diagnostic tools, they face challenges such as delayed results and false positives. Untargeted metabolomics has emerged as a complementary approach, offering comprehensive metabolic profiling and potential for novel biomarker discovery. We previously applied untargeted metabolomics to neonates with MSUD, identifying distinct metabolic signatures. Objective: This follow-up study investigates metabolic changes and biomarkers in pediatric MSUD patients and explores shared dysregulated metabolites between neonatal and pediatric MSUD. Methods: Dried blood spot (DBS) samples from pediatric MSUD patients (n = 14) and matched healthy controls (n = 14) were analyzed using LC/MS-based untargeted metabolomics. Results: In pediatric MSUD, 3716 metabolites were upregulated and 4038 downregulated relative to controls. Among 1080 dysregulated endogenous metabolites, notable biomarkers included uric acid, hypoxanthine, and bilirubin diglucuronide. Affected pathways included sphingolipid, glycerophospholipid, purine, pyrimidine, nicotinate, and nicotinamide metabolism, and steroid hormone biosynthesis. Seventy-two metabolites overlapped with neonatal MSUD cases, some exhibiting inverse trends between age groups. Conclusion: Untargeted metabolomics reveals that the metabolic profiling of MCUD pediatric patients different from that of their controls. Also, there are valuable age-specific and shared metabolic alterations in MSUD, enhancing the understanding of disease progression in MSUD patients. This supports its utility in improving diagnostic precision and developing personalized treatment strategies across developmental stages.

A Risk-Based, Qtpp-Driven Framework For Semi-Solid Extrusion 3d Printing of Personalized Medicines: Integrating Hospital Compounding and Clinical Trial Regulation.

BackgroundMaple syrup urine disease (MSUD) is an inherited metabolic disorder caused by a deficiency in the activity of the hepatic branched-chain α-ketoacid dehydrogenase (BCKDH) complex, which leads to the toxic accumulation of three branched-chain amino acids (BCAAs) and their respective α-ketoacid, resulting in severe neurotoxicity, coma and even death without effective therapeutic measures.MethodsIn this study, we established the patient induced pluripotent stem cells (iPSC)-derived hepatic organoids (HOs), analyzed the characteristics, and applied adenine base editor (ABE8e) to correct a mutation (T322I) of the BCKDHB (branched chain keto acid dehydrogenase E1, beta polypeptide) gene in patient induced pluripotent stem cells (iPSC)-derived hepatic organoids (HOs). qRT-PCR and western blot analysis were performed to assess the expression level of BCKDHA (branched chain keto acid dehydrogenase E1, alpha polypeptide) and BCKDHB. The effects of base editing were comprehensively analyzed using both bulk RNA sequencing and single-cell RNA sequencing (scRNA-Seq).ResultsImmunofluorescence and RT-PCR arrayed the high expression of hepatoblast specific proteins in HOs, such as α-1-anti-trypsin (A1AT), hepatocyte nuclear factor-4-alpha (HNF4A), cytokeratin18 (CK18), albumin (ALB), cytochrome P450 family 3 subfamily A member 4 (CYP3A4) and cytochrome P450 family 3 subfamily A member 7(CYP3A7). Functional experiments indicated that these HOs recapitulated characteristics of hepatocytes like glycogen accumulation, low-density lipoprotein (LDL) uptake, indocyanine green (ICG) uptake and release as well as quantitation of ALB and urea from HOs. The levels of BCKDHA and BCKDHB were dramatically decreased in MSUD-HOs compared with control-HOs (P < 0.01) detected by qRT-PCR, western blot and immunofluorescence. Deep sequencing and whole genome sequencing (WGS) demonstrated that the correction of BCKDHB mutation in patient iPSC-derived HOs caused high on-target gene editing without any detectable off-target effects. Moreover, the corrected MSUD-HOs exhibited restored BCKDH enzymatic function and reduced BCAAs level. The transcriptome analysis indicates that the MSUD-HOs with BCKDHB mutation reduced mRNA level of regulating metabolism associated with liver mitochondrial function, while the corrected MSUD-HOs rescued those processes after ABE8e correction. The scRNA-Seq analysis further validated the rescue effects of BCKDH function after gene editing.ConclusionOur study provides reliable evidence that ABE8e is highly efficient and safe in correcting patient-derived HOs from MSUD, indicating the feasibility to be a transformative treatment for genetic hepatic diseases like MSUD.Graphical abstractSupplementary InformationThe online version contains supplementary material available at 10.1186/s13287-025-04630-w.

Branched-chain amino acids (BCAA) leucine, isoleucine, and valine are metabolized by complex branched-chain ketoacids dehydrogenase (BCKDH). In Maple Syrup Urine Disease (MSUD), the BCKDH complex has its activity blocked by a genetic mutation, compromising the BCAA metabolism and leading to the accumulation of these BCAA, related to neurological damage in this disease. Thus, minocycline is a broad-spectrum antibiotic, bacteriostatic, and studies have shown benefits in neurodegenerative disease progression, like reduction of oxidative stress, inflammation, and downregulation of molecular pathways, such as apoptosis. Therefore, we make the hypothesis that the minocycline can ameliorate oxidative stress in the MSUD model. For this, we used 7-day-old male rats, who were treated with BCAA (leucine 393.42mg/kg, isoleucine 121.66mg/kg and valine 126.4mg/kg) or saline solution (0,9%) subcutaneously, water, or minocycline (50mg/kg) via gavage. Our results show that the MSUD group presents an increase in DCFH oxidation and TBARS levels, as well as a decrease in sulfhydryl content, related to oxidative species production, lipid and protein damage, and minocycline treatment rescues this damage found. In antioxidant activity, we found an increase in SOD activity also, a decrease in CAT in all groups studied compared to the control group. So, our results present positive effects of minocycline in MSUD, showing a potential use in this disease; moreover, more studies are necessary to understand the role of this molecule in this disease.

Maple Syrup Urine Disease (MSUD) and Type 1 Diabetes Mellitus (T1DM) are two distinct metabolic disorders with unique dietary management requirements. While MSUD necessitates strict restriction of branched-chain amino acids (BCAAs), T1DM requires precise carbohydrate counting to maintain optimal glycemic control. We report two cases of patients diagnosed with both MSUD and T1DM, highlighting the challenges and strategies in dietary management. Case 1, a 5-year-old girl, was diagnosed with T1DM after presenting with hyperglycemia and metabolic acidosis, despite previously stable MSUD management. The dietary regimen was modified to include a leucine-free amino acid formula and controlled carbohydrate intake to stabilize both leucine and glucose levels. Case 2, an 11-year-old boy with the diagnosis of MSUD, presented with hyperglycemia during a routine follow-up. Dietary management involved increasing the leucine-free formula while reducing carbohydrate intake to maintain metabolic control. Both cases emphasize the importance of individualized dietary plans, integrating BCAA restriction and carbohydrate regulation to prevent metabolic crises and achieve optimal glycemic control. These cases also underscore the need for a multidisciplinary approach involving pediatric endocrinologists, metabolic specialists, and dietitians to navigate the complexities of dual metabolic disorders effectively. Further studies are warranted to explore long-term outcomes and potential therapeutic targets in patients with concurrent MSUD and T1DM.

Although dermatology relies primarily on sight and touch, clinicians often overlook smell despite encountering diagnostic odors. We reviewed PubMed and Google Scholar for articles on disease-related cutaneous odors. Bacterial and fungal infections emit characteristic malodors, while genetic and metabolic disorders (eg, Darier disease, trimethylaminuria, phenylketonuria, maple syrup urine disease) and organ dysfunction (renal and hepatic failure) produce unique scents. Preliminary evidence also suggests melanoma may have a distinct odor detectable by canines. Although objective odor measurement remains challenging, incorporating olfaction could enhance diagnosis and merits further research.

Liver Transplantation for Maple Syrup Urine Disease: Outcomes Analysis of 245 Liver Transplant Recipients from the United Network for Organ Sharing Registry

Maple syrup urine disease (MSUD) is a rare, autosomal recessive metabolic disorder caused by a genetic defect in the metabolism of branched-chain amino acids. This metabolic disorder in children can affect tooth development and increase the prevalence of caries. During dental treatment, the systemic conditions of these patients should be considered, procedures that may create metabolic stress should be avoided, and treatment planning should be undertaken with a multidisciplinary approach. This case report examines conservative dentistry approaches in two pediatric patients diagnosed with MSUD. The study aimed to address the pain, functional, and aesthetic needs of two siblings diagnosed with MSUD, alleviate the adverse effects on gingival health, and treat tooth sensitivity. In both cases, invasive procedures were avoided, and treatments were performed using noninvasive methods whenever possible. Behavior management techniques increased patient compliance, and local anesthesia administration and procedure durations were planned with consideration of metabolic stress factors. Preventive treatments were implemented to prevent premature and unnecessary tooth loss, and patients were invited for follow-up appointments at six-month intervals. The purpose of this case report is to highlight the points to consider during dental treatment in individuals diagnosed with MSUD and to demonstrate the effectiveness of the conservative approach.

BackgroundDiabetic ketoacidosis is an acute, potentially life-threatening, metabolic complication and often first presentation of type 1 diabetes (T1D) mellitus. Here, we investigated the metabolic and lipid profiles from pediatric patients with T1D, at initial diagnosis and after two weeks of insulin treatment, employing findings from patients affected by maple syrup urine disease (MSUD) and the Recipient Epidemiology and Donor Evaluation Study (REDS) III RBC Omics.Methods27 patients with newly onset T1D were assessed at the University of Campania “L. Vanvitelli” at first diagnosis and 2 weeks after therapy with insulin. As part of the REDS-III RBC Omics, whole blood was collected from 13,091 healthy blood donors. Whole blood was also collected from 3 patients with MSUD by biallelic inactivating mutation of BCKDHA. Metabolomics and Lipidomics were performed via UHPLC-MS/MS.ResultsOur findings highlight a newly identified associations among short-chain hydroxyacyl-carnitines, ketoacidosis, and hematological alterations in T1D. An associative linkage with SNPs in the regions coding for branched chain ketoacid dehydrogenase A and B (BCDHKA/B) is noted by leveraging measurements of the same metabolites in over 13,000 healthy genetically characterized donor volunteers. MSUD, a rare genetic disorder characterized by inactivating mutations of the BCDHKA gene leading to inability to metabolize branched-chain amino acids, manifests a strong association between the branched-chain amino acid-derived ketoacids, associated acyl-carnitines, and acidosis.ConclusionsThese results indicate that T1D hematological alterations at onset might act as biomarkers linked to circulating levels of short-chain acyl-carnitines, providing risk stratification for T1D and potentially for MSUD. Carnitine metabolism may be a promising therapeutic target for both diseases.

Newborn screening (NBS) is one of the most impactful population-based public health programs, exemplifying the power of early detection and timely intervention in preventive medicine. Its primary goal is to identify metabolic and genetic disorders that are often asymptomatic at birth but can lead to serious morbidity or mortality if left untreated. NBS began in the 1960s, when Robert Guthrie introduced dried blood spot (DBS) collection and a bacterial inhibition assay to detect phenylketonuria (PKU). Following the success of PKU screening and treatment, NBS gradually expanded to include other conditions such as congenital hypothyroidism, galactosemia, maple syrup urine disease, congenital adrenal hyperplasia, and hemoglobinopathies—though each was added individually. The introduction of tandem mass spectrometry (MS/MS) in the 1990s transformed NBS by enabling simultaneous detection of multiple disorders from a single DBS sample. Advances in microfluidics and molecular techniques further enhance the capabilities of NBS. However, rapid expansion led to significant variability in NBS programs. To address this, the Recommended Uniform Screening Panel (RUSP) was established in 2006 and currently includes 38 core conditions and 26 secondary conditions. Emerging genomic technologies—such as targeted DNA panels, whole exome sequencing, and whole genome sequencing—are further expanding the scope of NBS, though challenges related to cost, ethics, and interpretation of uncertain findings persist. Artificial intelligence (AI) and machine learning offer new opportunities to enhance diagnostic accuracy and follow-up. Expanding NBS globally will require affordable, scalable technologies and ongoing collaboration across disciplines.

Mitochondrial HMG-CoA synthase-2 (HMGCS2) deficiency is characterized by hypoketotic hypoglycemia, metabolic acidosis, hepatomegaly, and encephalopathy with onset between 3 and 36 months of age. Approximately 50 cases were reported worldwide. We describe two patients with HMGCS2 deficiency. Patient 1 presented on day of life 7 with a sepsis-like condition, coma, metabolic acidosis, and marked elevation of ammonium level at 1081 μmol/L. Metabolic screening demonstrated elevated valine and leucine/isoleucine concentrations, resembling maple syrup urine disease (MSUD). The patient received a blood exchange transfusion, which lowered the ammonium level to 92 μmol/L. Urine organic acid analysis did not confirm MSUD. At 1 year and 4 months, the patient experienced acute decompensation again. Exome sequencing revealed a homozygous HMGCS2 variant, c.1502G>C (p.Arg501Pro). Patient 2, an older sibling of Patient 1, was healthy but diagnosed through genetic testing. Both patients exhibited abnormal biochemical profiles, including dicarboxylic aciduria and increased urinary excretion of 4-hydroxy-6-methyl-2-pyrone (4-HMP) after 8 h of fasting, suggesting that a clinically asymptomatic patient, like Patient 2, may eventually develop acute decompensation. Therefore, preemptive treatment with fasting avoidance with or without l-carnitine during intercurrent illness should be advised. The present cases were the second and third patients of p.Arg501Pro homozygosity. The elevated branched-chain amino acids in the metabolic screening (without including alloisoleucine) and the described organic acid profile can be found during the catabolic state, resembling MSUD, and severe hyperammonemia is an uncommon phenotype and an exception to neonatal decompensation in HMGCS2 deficiency. Our findings demonstrated intrafamilial variability and expanded the clinical and biochemical spectrum of HMGCS2 deficiency.

Inborn errors of metabolisms (IEMs) are group of diseases caused by mutations in single genes, leading to buildup of metabolites, toxic or disrupt normal cellular function. The etiological relation of metabolic disorders has been uncovered through study of metabolite amyloids. Various metabolites that accumulate in IEMs have been reported to self-assemble into organized structures. These structures exhibit similar physicochemical properties as proteinaceous amyloid fibrils. Our study illustrates the aggregation properties of branched chain amino acids (BCAAs), isoleucine, leucine, and valine that accumulate in maple syrup urine disease (MSUD) to investigate their propensities to assemble into amyloid-like fibrils. The structural morphologies of BCAAs are studied via microscopic techniques. Further, characterization techniques are employed to understand the physicochemical properties of the self-assemblies and their underlying mechanism. The amyloid-like nature of these aggregates is confirmed using thioflavin T and congo red assays. The (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay reveals BCAAs are cytotoxic and significantly decrease cell viability. This study plays a key role in understanding the physicochemical properties of MSUD in the context of amyloid diseases, possibly paving the way for the development of its therapeutic solutions in the future.

Maple syrup urine disease (MSUD) is a rare inherited metabolic disease. Breakdown of branched-chain amino acids (leucine, isoleucine, valine) is impaired or absent, which results in metabolite accumulation causing neurotoxicity. With strict therapy adherence (protein restricted MSUD-diet and amino acid supplementation), nearly normal plasma leucin levels can be achieved. However, therapy interruption or catabolic conditions (illness, operation, fasting) can rapidly lead to life-threatening metabolic decompensation. In this report we present the case of a 50 year-old woman who was referred to our hospital with impaired level of consciousness due to delayed recognition of MSUD decompensation. The aim is to increase awareness for this condition and repeat the central treatment aspects.

Acute cerebellar ataxia in a patient with maple syrup urine disease: a case report

Maple Syrup Urine Disease (MSUD) is an inherited metabolic disorder caused by mutations in the genes BCKDHA, BCKDHB, DLD, and DBT, which are involved in the breakdown of branched-chain amino acids (BCAAs). The research aimed to characterize these mutations among MSUD patients from different regions and ethnic groups within Azerbaijan. Polymerase Chain Reaction (PCR) was used to amplify the genes BCKDHA, BCKDHB, DLD, and DBT. Blood samples were collected from 940 patients diagnosed with MSUD, and exome sequencing along with Sanger sequencing were employed for detailed analysis. The study involved patients from various regions of Azerbaijan, including Sheki-Zagatala, Guba-Khachmaz, Lankaran-Astara, and Baku. These areas have diverse ethnic groups, with the study specifically noting patients from the Azerbaijani Turk and Lezgi ethnic groups in the Guba-Khachmaz zone. DBT gene: The 1199A&gt;G mutation was found in a homozygous form in one patient. BCKDHB gene: The 508C&gt;T mutation was found in a homozygous form in a second patient. BCKDHB gene: In a third patient, the 972C&gt;T (exon 9) and 1221A&gt;G (exon 10) mutations were found in a compound heterozygous form. The 508C&gt;T mutation (BCKDHB gene) caused a Lys-Gly change at position 332 in the corresponding polypeptide. The 972C&gt;T and 1221A&gt;G mutations in the BCKDHB gene caused changes at positions 673 and 947, resulting in Arg673Ser and Phe947Gly substitutions. The 1199A&gt;G mutation in the DBT gene caused a Lys508Gln change at the corresponding position. Using Swiss modeling software, the protein structures were analyzed. The 508(C&gt;T) mutation affected the protein helix structure. The Arg673Ser and Phe947Gly mutations were observed in the protein coils. The Lys907Gly mutation resulted in an extension of the β-sheet structure. The study highlights the importance of genetic testing for MSUD, especially in regions with diverse ethnic populations like Azerbaijan. The novel mutations discovered provide essential information for genetic counseling, diagnosis, and treatment of MSUD. Furthermore, the territorial and ethnic distribution of these mutations offers valuable insights into molecular diagnostics and understanding the genetic diversity of the disease in Azerbaijani populations. The findings underline the critical role of identifying genetic mutations in MSUD, facilitating early diagnosis and personalized treatments. Additionally, the study demonstrates the significance of regional and ethnic variations in genetic diseases, which can inform better-targeted healthcare strategies for diverse populations.

Maple Syrup Urine Disease (MSUD) is an autosomal recessive disorder caused by mutations in the BCKDH complex, leading to the accumulation of branched-chain amino acids. Severe cases of MSUD often require liver transplantation (LT) to restore metabolic stability and prevent neurological complications. Domino liver transplantation (DLT) using MSUD livers has emerged as an innovative approach to expand the donor pool, leveraging the fact that MSUD-affected livers can function normally in recipients without developing MSUD due to extrahepatic BCKDH activity. This study retrospectively reviews the experience at King Fahad Specialist Hospital in Dammam, where seven patients with MSUD underwent LT, with their explanted livers subsequently transplanted into seven other recipients. The results demonstrate the feasibility and safety of this approach, with a 100% survival rate for MSUD patients at a median follow-up of 2.9 years. For the domino recipients, the 3-year graft and patient survival rate was 71.4%, with two graft-related fatalities. The study highlights the importance of careful recipient selection, optimal graft-to-recipient weight ratio, and the potential for hybrid dual graft transplantation in cases where graft volume is insufficient. The findings suggest that DLT using MSUD livers is a viable option, particularly in regions with limited deceased donor activity, and should be considered in mature liver transplant programs to address organ shortages.