Glycogen Storage Disease Research Articles

Induced pluripotent stem cell (iPSC) modeling validates reduced GBE1 enzyme activity due to a novel variant, p.Ile694Asn, found in a patient with suspected glycogen storage disease IV

BackgroundGlycogen Storage disease type 4 (GSD4), a rare disease caused by glycogen branching enzyme 1 (GBE1) deficiency, affects multiple organ systems including the muscles, liver, heart, and central nervous system. Here we report a GSD4 patient, who presented with severe hepatosplenomegaly and cardiac ventricular hypertrophy. GBE1 sequencing identified two variants: a known pathogenic missense variant, c.1544G>A (p.Arg515His), and a missense variant of unknown significance (VUS), c.2081T>A (p. Ile694Asn). As a liver transplant alone can exacerbate heart dysfunction in GSD4 patients, a precise diagnosis is essential for liver transplant indication. To characterize the disease-causing variant, we modeled patient-specific GBE1 deficiency using CRISPR/Cas9 genome-edited induced pluripotent stem cells (iPSCs). MethodsiPSCs from a healthy donor (iPSC-WT) were genome-edited by CRISPR/Cas9 to induce homozygous p.Ile694Asn in GBE1 (iPSC-GBE1-I694N) and differentiated into hepatocytes (iHep) or cardiomyocytes (iCM). GBE1 enzyme activity was measured, and PAS-D staining was performed to analyze polyglucosan deposition in these cells. ResultsiPSCGBE1-I694N differentiated into iHep and iCM exhibited reduced GBE1 protein level and enzyme activity in both cell types compared to iPSCwt. Both iHepGBE1-I694N and iCMGBE1-I694N showed polyglucosan deposits correlating to the histologic patterns of the patient's biopsies. ConclusionsiPSC-based disease modeling supported a loss of function effect of p.Ile694Asn in GBE1. The modeling of GBE1 enzyme deficiency in iHep and iCM cell lines had multi-organ findings, demonstrating iPSC-based modeling usefulness in elucidating the effects of novel VUS in ultra-rare diseases.

Paediatric Liver Transplant at Army Liver Transplant Unit, Pakistan; A Four-Year Data

Objective: To re-examine the data about survival, prognosis, and complications of twenty-five paediatric liver transplant procedures carried out at Army Liver Transplant Unit, Pak Emirates Military Hospital Rawalpindi, Pakistan. Study Design: Retrospective longitudinal study. Place and Duration of Study: Army Liver Transplant Unit, Pak Emirates Military Hospital, Rawalpindi, Pakistan, from Jan 2016 to Feb 2020. Methodology: The procedural and follow-up data regarding twenty-five pediatric liver transplants was reviewed, and demographic variables, transplant indications and outcomes were documented. Results: The donation was entirely from living donors. Recipients included 12 boys and 13 girls of mean age 5.8±2.00 years. The stay at the hospital averaged 18±5.6 days. Indications in the order of frequency of encounter included 9(36%) cases of Cryptogenic liver cirrhosis, 4(16%) cases of progressive familial intrahepatic cholestasis, 3(12%) cases of Wilson’s disease, 2(8%) cases of Tyrosinemia, congenital hepatic fibrosis and biliary atresia each and one patient (4%) of Criggler-Najjar syndrome, glycogen storage diseases and autoimmune liver disease each. Major complications included viral infections, thrombosis of the portal vein and hepatic artery, bile leak and post-transplant diaphragmatic hernia. 20(80%) recipients were recorded to have survived during the follow-up. Conclusion: Encouraging results are noted, particularly a high survival rate (20 out of 25) and low complications (few and only well-known in this age group).

Intestinal microbiota composition of children with glycogen storage Type I patients

AimDietary therapy of glycogen storage disease I (GSD I) is based on frequent feeding, with a high intake of complex carbohydrates (supplied by uncooked cornstarch), restriction of sugars, and a lower amount of lipids. There is limited information about the dietary regimen in patients with GSD, which might affect the intestinal luminal pH and microbiota composition. The aim of this study to investigate the intestinal microbiota composition in patients with GSD receiving diet treatment.MethodTwelve patients who were followed up with GSD I after the diagnosis receiving diet therapy and 11 healthy children have been enrolled. Intestinal microbiota composition was evaluated by 16 s rRNA gene sequencing.ResultsA significant difference was found for beta-diversity between the GSD group and controls. A significantly lower abundance of Firmicutes and higher abundance of Actinobacteria was found in GSD group compared to the controls. Akkermansia, Pseudoalteromonas, Uruburella, and Castellaniella were dominant in the GSD patients at the genus level, while Faecalibacterium, Bacterioides, Gemmiger, Parabacteroides in the control group. At species level, Faecalibacterium prausnitzii decreased, and Akkermansia muciniphila were dominant in children with GSD.DiscussionThere is a substantial change in the composition of the gut microbiota, reduction of F. prausnitzii and an increase of A. muciniphila in children with GSD receiving consumption of uncooked cornstarch. Alterations of the intestinal microbiota might be related with the disease itself or dietary restrictions in patients with GSD, however, in certain condition, dysbiosis can negatively affect the course and make it difficult to control the disease.

Defect in degradation of glycogenin-exposed residual glycogen in lysosomes is the fundamental pathomechanism of Pompe disease.

Pompe disease is a lysosomal storage disorder that preferentially affects muscles, and it is caused by GAA mutation coding acid alpha-glucosidase in lysosome and glycophagy deficiency. While the initial pathology of Pompe disease is glycogen accumulation in lysosomes, the special role of the lysosomal pathway in glycogen degradation is not fully understood. Hence, we investigated the characteristics of accumulated glycogen and the mechanism underlying glycophagy disturbance in Pompe disease. Skeletal muscle specimens were obtained from the affected sites of patients and mouse models with Pompe disease. Histological analysis, immunoblot analysis, immunofluorescence assay, and lysosome isolation were utilized to analyze the characteristics of accumulated glycogen. Cell culture, lentiviral infection, and the CRISPR/Cas9 approach were utilized to investigate the regulation of glycophagy accumulation. We demonstrated residual glycogen, which was distinguishable from mature glycogen by exposed glycogenin and more α-amylase resistance, accumulated in the skeletal muscle of Pompe disease. Lysosome isolation revealed glycogen-free glycogenin in wild typemouse lysosomes and variously sized glycogenin in Gaa-/- mouse lysosomes. Our study identified that a defect in the degradation of glycogenin-exposed residual glycogen in lysosomes was the fundamental pathological mechanism of Pompe disease. Meanwhile, glycogenin-exposed residual glycogen was absent in other glycogen storage diseases caused by cytoplasmic glycogenolysis deficiencies. In vitro, the generation of residual glycogen resulted from cytoplasmic glycogenolysis. Notably, the inhibition of glycogen phosphorylase led to a reduction in glycogenin-exposed residual glycogen and glycophagy accumulations in cellular models of Pompe disease. Therefore, the lysosomal hydrolysis pathway played a crucial role in the degradation of residual glycogen into glycogenin, which took place in tandem with cytoplasmic glycogenolysis. These findings may offer a novel substrate reduction therapeutic strategy for Pompe disease. © 2024 The Pathological Society of Great Britain and Ireland.

Diagnosis and management of glycogen storage diseases

Diagnosis and management of glycogen storage diseases

A clinical candidate (VAL-1221) capable of treating multiple glycogen storage diseases including Lafora and other neurological polyglucosan disorders

A clinical candidate (VAL-1221) capable of treating multiple glycogen storage diseases including Lafora and other neurological polyglucosan disorders

A simple, non-invasive method for the diagnosis of glycogen storage disease type III in two patients with a similar facial appearance

A simple, non-invasive method for the diagnosis of glycogen storage disease type III in two patients with a similar facial appearance

Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders.

Glycogen synthase 1 (GYS1), the rate-limiting enzyme in muscle glycogen synthesis, plays a central role in energy homeostasis and has been proposed as a therapeutic target in multiple glycogen storage diseases. Despite decades of investigation, there are no known potent, selective small-molecule inhibitors of this enzyme. Here, we report the preclinical characterization of MZ-101, a small molecule that potently inhibits GYS1 in vitro and in vivo without inhibiting GYS2, a related isoform essential for synthesizing liver glycogen. Chronic treatment with MZ-101 depleted muscle glycogen and was well tolerated in mice. Pompe disease, a glycogen storage disease caused by mutations in acid α glucosidase (GAA), results in pathological accumulation of glycogen and consequent autophagolysosomal abnormalities, metabolic dysregulation, and muscle atrophy. Enzyme replacement therapy (ERT) with recombinant GAA is the only approved treatment for Pompe disease, but it requires frequent infusions, and efficacy is limited by suboptimal skeletal muscle distribution. In a mouse model of Pompe disease, chronic oral administration of MZ-101 alone reduced glycogen buildup in skeletal muscle with comparable efficacy to ERT. In addition, treatment with MZ-101 in combination with ERT had an additive effect and could normalize muscle glycogen concentrations. Biochemical, metabolomic, and transcriptomic analyses of muscle tissue demonstrated that lowering of glycogen concentrations with MZ-101, alone or in combination with ERT, corrected the cellular pathology in this mouse model. These data suggest that substrate reduction therapy with GYS1 inhibition may be a promising therapeutic approach for Pompe disease and other glycogen storage diseases.

Report of an Iranian child with chronic abdominal pain and constipation diagnosed as glycogen storage disease type IX: a case report

BackgroundGlycogen storage disease type IX is a rare disorder that can cause a wide variety of symptoms depending on the specific deficiency of the phosphorylase kinase enzyme and the organs it affects.Case presentationA 4-and-a-half-year-old Caucasian girl was referred to our clinic with a liver biopsy report indicating a diagnosis of glycogen storage disease. Prior to being referred to our clinic, the patient had been under the care of pediatric gastroenterologists. The patient’s initial symptoms included chronic abdominal pain, constipation, and elevated liver transaminase. With the help of the pediatric gastroenterologists, cholestasis, Wilson disease, and autoimmune hepatitis were ruled out. Given that glycogen storage diseases type I and type III are the most common, we initially managed the patient with frequent feedings and a diet that included complex carbohydrates such as a corn starch supplement and a lactose restriction. Following an unfavorable growth velocity and hepatomegaly during the follow-up period, genetic analysis was conducted, which revealed a novel mutation of the phosphorylase kinase regulatory subunit beta gene— a c.C412T (P.Q138x) mutation. As the diagnosis of glycogen storage disease type IX was confirmed, the treatment regimen was altered to a high protein diet (more than 2 g/kg/day) and a low fat diet.ConclusionGiven the mild and varied clinical manifestations of glycogen storage disease type IX, it is possible for the diagnosis to be overlooked. It is important to consider glycogen storage disease type IX in children who present with unexplained hepatomegaly and elevated transaminase levels. Furthermore, due to the distinct management of glycogen storage disease type IX compared with glycogen storage disease type I and glycogen storage disease type III, genetic analysis is essential for an accurate diagnosis.

Repurposing empagliflozin in individuals with glycogen storage disease Ib: A value-based healthcare approach and systematic benefit-risk assessment.

Off-label repurposing of empagliflozin allows pathomechanism-based treatment of neutropenia/neutrophil-dysfunction in glycogen storage disease type Ib (GSDIb). From a value-based healthcare (VBHC) perspective, we here retrospectively studied patient-reported, clinical and pharmacoeconomic outcomes in 11 GSDIb individuals before and under empagliflozin at two centers (the Netherlands [NL], Austria [AT]), including a budget impact analysis, sensitivity-analysis, and systematic benefit-risk assessment. Under empagliflozin, all GSDIb individuals reported improved quality-of-life-scores. Neutrophil dysfunction related symptoms allowed either granulocyte colony-stimulating factor cessation or tapering. Calculated cost savings per patient per year ranged between € 6482-14 190 (NL) and € 1281-41 231 (AT). The budget impact analysis estimated annual total cost savings ranging between € 75 062-225 716 (NL) and € 37 697-231 790 (AT), based on conservative assumptions. The systematic benefit-risk assessment was favorable. From a VBHC perspective, empagliflozin treatment in GSDIb improved personal and clinical outcomes while saving costs, thereby creating value at multiple pillars. We emphasize the importance to reimburse empagliflozin for GSDIb individuals, further supported by the favorable systematic benefit-risk assessment. These observations in similar directions in two countries/health care systems strongly suggest that our findings can be extrapolated to other geographical areas and health care systems.

Pediatric Cardiomyopathies from the Landscape of Inherited Metabolic Disorders in Southeastern Turkey

Background: Cardiomyopathy (CM) is an important factor affecting inherited metabolic disorders (IMDs). Therefore, documentation of real-world data can increase awareness, and early diagnosis and treatment may improve the outcome. Objectives: The aim of this study was to delineate the underlying etiologies and clinical findings of patients with CM due to IMDs. Methods: In this single-center retrospective study, we aimed to examine the demographic, clinical, and echocardiographic data and prognosis of patients aged 0 - 18 who were diagnosed with CM associated with IMDs between 2010 and 2020. Results: A total of 102 patients were included in the study. Families with consanguineous parents constituted 84.3% of the study population. The mean age of the patients at the time of diagnosis of CM was 26.2 ± 28.2 months. Eighty-six (84.3%) of the patients were diagnosed with hypertrophic CM (HCM), 12 (11.7%) with dilated CM (DCM), and 4 (3.9%) with mixt-type CM. Of the patients, 60 (58.8%) had glycogen storage disease (GSD), 17 (16.6%) had lysosomal storage disorders (LSDs), 11 (10.7%) had fatty acid oxidation disorders, 11 (10.7%) had mitochondrial disorders, and 3 (2.9%) had amino acid and organic acid metabolism disorders. Arrhythmia was detected in 24 patients (23.5%). Fifty-six patients received enzyme replacement therapy (ERT). The echocardiographic parameters of the Pompe patients improved significantly with ERT. The mean follow-up period was 60.9 ± 54.6 months. Thirty-eight (36.1%) of 95 patients with regular follow-up died. Cardiomyopathy type did not affect mortality. Conclusions: Increasingly, cardiac complications have been defined as IMDs. Evaluation should be made in terms of IMDs in unexplained CM and rhythm disorders. On the other hand, patients with certain IMDs should be regularly screened for cardiac complications.

Toward an Understanding of GSD5 (McArdle disease): How Do Individuals Learn to Live with the Metabolic Defect in Daily Life.

Glycogen storage disease type 5 (GSD) is an autosomal recessive inherited metabolic myopathy caused by a deficiency of the enzyme muscle glycogen phosphorylase. Individuals with GSD5 experience physical activity intolerance. This patient-led study aimed to capture the daily life experiences of GSD5, with a focus on adapting to and coping with their physical activity intolerance. An online survey was composed in close collaboration with patient organizations. It consisted of customized and validated questionnaires on demographics, general health and comorbidities, physical activity, psychosocial well-being and functioning, pain, fatigue and adapting to and coping with GSD5. One hundred sixty-two participants (16 countries) participated. The majority, n = 86 (69%) were from the Netherlands, USA or UK. We observed a high rate of misdiagnosis prior to GSD5 diagnosis (49%), surprisingly a relatively high proportion had not been diagnosed by DNA testing which is the gold standard. Being diagnosed had a strong impact on emotional status, daily life activities and important life choices. A large proportion had not received any rehabilitation (41%) nor medical treatment (57%) before diagnosis. Engagement in vigorous and moderate physical activity was reduced. Health related quality of life was low, most likely related to low physical health. The median Fatigue Severity Score was 4.3, indicating moderate to severe fatigue. Participants themselves had found various ways to adapt to and cope with their disability. The adaptations concerned all aspect of their life, including household chores, social and physical activities, and work. In addition to lack of support, participants reported limited availability of information sources. Participants have provided guidance for newly diagnosed people, including the advice to accept one's limited abilities and maintain an active lifestyle. We conclude that adequate counseling on ways of adapting and coping is expected to increase both health-related quality of life and physical activity.

Assessment of thyroid function in children and adolescents with chronic liver diseases

Introduction The majority of hepatic patients are clinically euthyroid. However, liver disorders may alter thyroid hormone metabolism, including substantial abnormalities of either euthyroid sick syndrome (ESS), autoimmune thyroid disorders, or subclinical hypothyroidism (SH). But there are few studies conducted on children with chronic liver diseases (CLD) to assess thyroid functions. Aim The study aimed to evaluate thyroid profiles in patients with CLD. Patients and methods An observational, cross-sectional study including patients with CLD attending Hepatology Clinic at Alexandria University Children’s Hospital from June 2021 to June 2022. One hundred and two children were included and a history taking and clinical examination were performed. Assessment of severity using a modified Child–Pugh score was done. Laboratory investigations in the form of liver, lipid, and thyroid profiles were done. Results One hundred and two children with CLD were included in this study, 50 (49.0%) females and 52 (51.0%) males. The most common diagnosis in the studied cases was autoimmune hepatitis (24.5%), followed by glycogen storage disease. Out of 14 (13.7%) aberrant outcomes of thyroid function, seven (6.9%) patients had ESS, and seven (6.9%) individuals had SH. By univariate analysis, alkaline phosphatase and serum albumin level were significant risk factors for SH. Furthermore, melena and hepatic encephalopathy were significant risk factors for ESS. Conclusion Thyroid dysfunction might occur in CLDs either in the form of SH or ESS. The prevalence of thyroid disease in children with CLD exceeded 10%, which signifies the importance of screening for thyroid dysfunctions in this cohort.

Differentiation of oligosaccharide isomers by direct infusion multidimensional mass spectrometry.

Oligosaccharides demonstrate many bioactivities with applications in the pharmaceutical, cosmetic, and food industries. They also serve as biomarkers for various diseases including cancer and glycogen storage disorders. These make the structural characterization of oligosaccharides very important. Unfortunately, the structural diversity found in saccharides make their characterization challenging, necessitating the development of sophisticated instrumentation to enable isomer differentiation. Herein, we report the ability of halide (Cl- and Br-) adducts to enable direct differentiation of oligosaccharide isomers using conventional collision-induced dissociation (CID) tandem MS (MS/MS). The halide adducts were generated by direct infusion nano-electrospray ionization (nESI). For the first time, this traditional nESI CID MS/MS platform was used to differentiate stereoisomers of trisaccharides (cellotriose β(1 → 4) and maltotriose α(1 → 4), tetrasaccharides (cellotetraose and maltotetraose), and pentasaccharides (cellopentaose and maltopentaose)). In addition, the MS/MS of halide adducts enabled the differentiation of positional, structural, and linkage isomers from a total of 14 oligosaccharides. The isomer differentiation was realized by the generation of distinct diagnostic fragment ions in CID. We also performed principal component analysis using the entire range of MS/MS fragment ion profiles and found that negative-ion mode halide adduction provided more effective isomer differentiation compared with positive-ion mode sodium adduction. Finally, we demonstrated complex mixture analysis by spiking all 14 oligosaccharides into raw urine, of which we successfully distinguished species based on molecular weight (first dimension) and CID MS/MS fragmentation patterns as the second dimension separation. This work effectively showcases the potential to use direct infusion nESI-MS/MS to characterize synthetic oligosaccharide isomers in unpurified reaction mixture as well as from biofluids for diagnostic purposes.

“A Complex Conundrum”- Fanconi-Bickel Syndrome

Fanconi-Bickel Syndrome (FBS) is a rare form of Glycogen Storage Disease (GSD) type 11 characterised by massive hepatomegaly due to the buildup of glycogen and severe hypophosphatemic rickets due to a proximal renal tubular dysfunction. Since 1940, it has been initially known as hepatorenal glycogenesis with proximal renal tubular dysfunction. It is due to a pathogenic mutation of the GLUT-2 (glucose transporter) gene. Herein, present case report a young toddler who is the firstborn of 3rd-degree consanguinity, presented with rickets, recurrent respiratory tract infections, and hepatomegaly, and was subsequently diagnosed with FBS with the help of genetic studies, showing a mutation in the GLUT-2 gene. With less than 200 cases reported so far, this child represents a unique case with recurrent respiratory infections and developmental delay as presentations along with rachitic features.

Anesthetic management of glycogen storage disease type 1b during liver transplantation: a case report

The glycogen storage disease type 1b is a rare metabolic disease caused by the glucose 6-phosphate transporter disorder. This study presents a 10-year-old female patient with growth retardation, neutropenia and inflammatory bowel disease, severe hypoglycemia attacks before and during the surgery, and hepatocellular carcinoma who underwent liver transplantation. A multidisciplinary approach from the preoperative preparation stage is essential in addition to intraoperative intervention for hypoglycemia and lactic acidosis in the anesthetic management of these patients.

Glycogen storage disease type III: a mixed-methods study to assess the burden of disease.

Glycogen storage disease type III (GSD III) is a rare inherited disorder that results from a glycogen debranching enzyme deficiency. The purpose of this research was to collect data on the signs, symptoms, and impacts of GSD III from the perspective of adult patients and caregivers of individuals with GSD III. Online survey and qualitative interviews. Following institutional review board approval, adult patients and caregivers of children with GSD III were recruited through advocacy networks and clinical sites. If eligible, participants were consented, screened, and sent a survey and/or participated in a 60-min interview. The survey and interview included questions about family history, diagnosis, signs and symptoms, impacts, and management of GSD III. Conceptual models were developed following the analysis of results. In all, 29 adults and 46 caregivers completed the online survey and/or the interviews with 73 survey and 19 interview respondents. Adults and caregivers reported digestive, musculoskeletal, growth and physical appearance, and cardiac signs and symptoms. Liver conditions were reported by most respondents (83%). Adults and caregivers frequently reported impacts such as difficulty keeping up with peers (77%) and difficulty exercising/difficulty with physical activity (53%). Hypoglycemia was frequently reported in both adults and children, with more than half reporting hospitalizations due to hypoglycemia. Caregivers focused on hypoglycemia when reporting signs/symptoms that most interfere with their child's life and prevention of hypoglycemia as a desired outcome for an effective therapy. Adults most often reported muscle weakness as a top interfering symptom and the most important goal of a potential therapy. Impacts were also reported in activities of daily living, cognitive, emotional, work/school, and sleep domains. Individuals with GSD III experience a broad spectrum of symptoms and disease impacts. There is an unmet need for therapies that improve metabolic control, reduce the burden of dietary management, reduce fatigue and liver problems, and improve muscle strength and function.

PRKAG2 syndrome, a rare hypertrophic cardiomyopathy: a Brazilian long-term follow-up with extracardiac disorders.

This study aimed to provide a long-term follow-up of PRKAG2 syndrome and describe the new phenotypic aspects of the condition. PRKAG2 syndrome is a rare autosomal-dominant glycogen storage disease characterized by cardiac hypertrophy, ventricular pre-excitation, and conduction system disease. Fatal arrhythmias occur frequently. A family cohort of 66 participants was recruited. Clinical and genetic analyses were performed. Median age of 36.97±17.28 years, with 69.9% being men. Nineteen subjects carried the deleterious variant p.K290I of the PRKAG2 gene. This group experienced many malignant events, including eight pacemaker implants, three sudden cardiac deaths, five aborted cardiac arrests, four strokes, four premature neonatal deaths, two spontaneous abortions, five forceps deliveries, and 12 cesarean procedures. Extracardiac involvement, such as in neurocognitive and psychiatric disorders, has been observed only in carriers of mutations. Palpitations, Syncope, atrial fibrillation, atrial flutter, sinus pauses, and bradycardia were strongly and significantly associated with major or severe adverse events (sudden cardiac death, aborted cardiac arrest, pacemaker use, stroke, and congestive heart failure). Early diagnosis and intervention through antiarrhythmic drugs, anticoagulation, pacemaker implantation, radiofrequency catheter ablation, and cesarean section surgery improved the symptoms and survival rates. Mutations carriers were advised to avoid pregnancy. This study identified that the p.K291I_PRKAG2 mutation is associated with poor prognosis, highlighting the need for early intervention. Further research may uncover the potential connections between intellectual disability, miscarriage, and neonatal death in individuals with this syndrome.

Liver-directed gene therapy for inherited metabolic diseases.

Gene therapy clinical trials are rapidly expanding for inherited metabolic liver diseases whilst two gene therapy products have now been approved for liver based monogenic disorders. Liver-directed gene therapy has recently become an option for treatment of haemophilias and is likely to become one of the favoured therapeutic strategies for inherited metabolic liver diseases in the near future. In this review, we present the different gene therapy vectors and strategies for liver-targeting, including gene editing. We highlight the current development of viral and nonviral gene therapy for a number of inherited metabolic liver diseases including urea cycle defects, organic acidaemias, Crigler-Najjar disease, Wilson disease, glycogen storage disease Type Ia, phenylketonuria and maple syrup urine disease. We describe the main limitations and open questions for further gene therapy development: immunogenicity, inflammatory response, genotoxicity, gene therapy administration in a fibrotic liver. The follow-up of a constantly growing number of gene therapy treated patients allows better understanding of its benefits and limitations and provides strategies to design safer and more efficacious treatments. Undoubtedly, liver-targeting gene therapy offers a promising avenue for innovative therapies with an unprecedented potential to address the unmet needs of patients suffering from inherited metabolic diseases.

Glycogen storage disease type 1 (GSD1a) and the liver adenoma/ hepatocellular carcinoma (HCC) sequence: insights from whole genome sequencing (WGS)

Glycogen storage disease type 1 (GSD1a) and the liver adenoma/ hepatocellular carcinoma (HCC) sequence: insights from whole genome sequencing (WGS)