Search Results (9)

Background/Objectives: This study aims to identify genetic variants associated with early-onset inflammatory bowel disease (IBD) and to improve diagnostic and therapeutic approaches. In selected monogenic IBD cases, treatment included colchicine, interleukin-1 inhibitors, and hematopoietic stem cell transplantation. Methods: This study included patients with early-onset IBD, defined as IBD diagnosed before the age of 10, who were under follow-up at the Department of Pediatric Gastroenterology, Hacettepe University, and agreed to participate between December 2018 and April 2021. Whole-exome sequencing (WES) was performed prospectively in patients without a prior diagnosis of monogenic disease, while clinical and laboratory data were reviewed retrospectively. Identified variants were evaluated for pathogenicity using standard bioinformatics tools. Results: A total of 47 patients were enrolled, including 33 boys (70.2%) and 14 girls (29.8%). The median age at symptom onset was 36 months (IQR: 10–72), and the median age at diagnosis was 3.7 years (IQR: 1.5–7.6). Crohn’s disease was diagnosed in 53.2% (n = 25), ulcerative colitis in 38.3% (n = 18), and unclassified IBD in 8.5% (n = 4). Monogenic IBD was identified in 36.2% (n = 17) of patients, including nine with Familial Mediterranean Fever and others with glycogen storage disease type 1b (n = 2), XIAP deficiency, chronic granulomatous disease, DOCK8 deficiency, IL10 receptor alpha defect, LRBA deficiency, and NFKB2 deficiency (n = 1 each). A novel SLC29A3 gene variant (c.480_481delTGinsCA, p.V161I) (transcript ID: ENST00000479577.2) was identified in 76.6% (n = 36) of patients. Conclusions: This study underscores the importance of genetic variants in early-onset IBD, particularly MEFV and the novel NFKB2. The frequent detection of the SLC29A3 variant may suggest its potential involvement in the pathogenesis of the disease. Full article

Glycogen storage diseases (GSDs) are a group of carbohydrate metabolism disorders, most of which are inherited in autosomal recessive patterns. GSDs are of two types: those that have to do with liver and hypoglycaemia (hepatic GSDs) and those that are linked to neuromuscular presentation. This study aims to assess the impact of dietary intervention, including medium-chain triglyceride (MCT) oil, on anthropometric measurements, body composition analysis and metabolic parameters among Jordanian children and is expected to be the first in the country. A sample of 38 children with glycogen storage disease type 1 (GSD-1) (median age = 6.4 years) were on a diet that included uncooked cornstarch therapy and a fructose-, sucrose- and lactose-restricted diet. Patients started to take MCT oil along with the prescribed diet after the first body composition test. Patients’ nutritional status was re-evaluated three months later. The study results show that the percentage of patients who suffered from hypoglycaemia at the beginning of the study decreased significantly from 94.7% to 7.9% (p < 0.0001). The serum levels of triglycerides, cholesterol, uric acid and lactate decreased significantly after three months of intervention (100–71.1%, 73.7–21.1%, 97.4–52.6% and 94.7–18.4%, respectively). In contrast, there was no statistical difference in neutrophil count. Regarding clinical parameters, liver span was significantly reduced from (16.01 ± 2.65 cm) to (14.85 ± 2.26 cm) (p < 0.0001). There were significant improvements in growth parameters, including height-for-age and BMI-for-age for children aged ≥2 years (p = 0.034 and p = 0.074, respectively). Significant improvements in skeletal muscle mass and bone mineral content were also noticed at the end of the trial (p ≤ 0.05). In conclusion, medium-chain triglyceride therapy is found to improve biochemical and growth parameters in children with GSD-1 in Jordan. Full article

Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disease caused by variants in the GBE1 gene, which encodes the glycogen branching enzyme (GBE). GSD IV accounts for approximately 3% of all GSD. The phenotype of GSD IV ranges from neonatal death to mild adult-onset disease with variable hepatic, muscular, neurologic, dermatologic, and cardiac involvement. There is a paucity of literature and clinical and dietary management in GSD IV, and liver transplantation (LT) is described to correct the primary hepatic enzyme defect. Objectives: We herein describe five cases of patients with GSD IV with different ages of onset and outcomes as well as a novel GBE1 variant. Methods: This is a descriptive case series of patients receiving care for GSD IV at Reference Centers for Rare Diseases in Brazil and in the United States of America. Patients were selected based on confirmatory GBE1 genotypes performed after strong clinical suspicion. Results: Pt #1 is a Latin male with the chief complaints of hepatosplenomegaly, failure to thrive, and elevated liver enzymes starting at the age of 5 months. Before LT at the age of two, empirical treatment with corn starch (CS) and high protein therapy was performed with subjective improvement in his overall disposition and liver size. Pt #2 is a 30-month-old Afro-American descent patient with the chief complaints of failure to gain adequate weight, hypotonia, and hepatosplenomegaly at the age of 15 months. Treatment with CS was initiated without overall improvement of the symptoms. Pt #3.1 is a female Latin patient, sister to pt #3.2, with onset of symptoms at the age of 3 months with bloody diarrhea, abdominal distention, and splenomegaly. There was no attempt of treatment with CS. Pt #4 is an 8-year-old male patient of European descent who had his initial evaluation at 12 months, which was remarkable for hepatosplenomegaly, elevated ALT and AST levels, and a moderate dilatation of the left ventricle with normal systolic function that improved after LT. Pt #1, #3.2 and #4 presented with high levels of chitotriosidase. Pt #2 was found to have the novel variant c.826G > C p.(Ala276Pro). Conclusions: GSD IV is a rare disease with different ages of presentation and different cardiac phenotypes, which is associated with high levels of chitotriosidase. Attempts of dietary intervention with CS did not show a clear improvement in our case series. Full article

(1) Background: The treatment goal of ketogenic glycogen storage diseases (GSDs) is appropriate control of hypoglycemia and other disturbances such as dyslipidemia. Monitoring and treatment of ketosis are known to improve outcomes. We used breath analysis to identify volatile organic compounds (VOCs) that correlate with serum ketones in order to provide a non-invasive method of monitoring ketosis. (2) Methods: Consecutive children with ketogenic GSDs were recruited from a single center during routine admission to monitor serum glucose and ketone levels. Five breath samples were collected from every patient at the same time of blood draws. SIFT-mass spectrometry was used to analyze breath samples. Univariate linear mixed-effects regression models for 22 known VOCs and either serum ketones or glucose were performed. (3) Results: Our cohort included 20 patients aged 5–15 years with a mean BMI of 20 kg/m² (72% tile). Most patients had GSD type 0 (35%), while 25% had type IX. VOCs that showed a significant correlation with serum ketone levels included acetone (p < 0.0001), trimethylamine (p < 0.0001), pentane (p = 0.0001), 3-methylhexane (p = 0.0047), and carbon disulfide (p = 0.0499). No correlation was found between serum glucose and any VOC. (4) Conclusions: Breath analysis is a promising noninvasive tool that can be used to predict ketone serum levels in patients with GSD. Full article

Glycogen storage disease type V (GSDV, McArdle disease) is a rare genetic myopathy caused by deficiency of the muscle isoform of glycogen phosphorylase (PYGM). This results in a block in the use of muscle glycogen as an energetic substrate, with subsequent exercise intolerance. The pathobiology of GSDV is still not fully understood, especially with regard to some features such as persistent muscle damage (i.e., even without prior exercise). We aimed at identifying potential muscle protein biomarkers of GSDV by analyzing the muscle proteome and the molecular networks associated with muscle dysfunction in these patients. Muscle biopsies from eight patients and eight healthy controls showing none of the features of McArdle disease, such as frequent contractures and persistent muscle damage, were studied by quantitative protein expression using isobaric tags for relative and absolute quantitation (iTRAQ) followed by artificial neuronal networks (ANNs) and topology analysis. Protein candidate validation was performed by Western blot. Several proteins predominantly involved in the process of muscle contraction and/or calcium homeostasis, such as myosin, sarcoplasmic/endoplasmic reticulum calcium ATPase 1, tropomyosin alpha-1 chain, troponin isoforms, and alpha-actinin-3, showed significantly lower expression levels in the muscle of GSDV patients. These proteins could be potential biomarkers of the persistent muscle damage in the absence of prior exertion reported in GSDV patients. Further studies are needed to elucidate the molecular mechanisms by which PYGM controls the expression of these proteins. Full article

Central nervous system (CNS) involvement has been variously studied in pediatric neuromuscular disorders (NMDs). The primary goal of this study was to assess cognitive functioning in NMDs, and secondary aims were to investigate possible associations of cognitive impairment with motor impairment, neurodevelopmental delay, and genotype. This was a cross-sectional study of 43 pediatric patients, affected by six NMDs. Myotonic dystrophy type 1 (DM1) and glycogen storage disease type 2 (GSD2) patients had a delay on the Bayley-III scales. On Wechsler scales, DMD and DM1 patients showed lower FSIQ scores, with an intellectual disability (ID) in 27% and 50%, respectively. FSIQ was normal in Becker muscular dystrophy (BMD), GSD2, and hereditary motor sensory neuropathy (HMSN) patients, while higher individual scores were found in the spinal muscular atrophy (SMA) group. In the DM1 cohort, lower FSIQ correlated with worse motor performance (ρ = 0.84, p < 0.05), and delayed speech acquisition was associated with ID (p = 0.048), with worse cognitive impairment in the congenital than in the infantile form (p = 0.04). This study provides further evidence of CNS in some NMDs and reinforces the need to include cognitive assessment in protocols of care of selected pediatric NMDs. Full article

The association between bone mineral density (BMD) and hepatic glycogen storage diseases (GSDs) is still unclear. To evaluate the BMD of patients with GSD I, IIIa and IXα, a cross-sectional study was performed, including 23 patients (GSD Ia = 13, Ib = 5, IIIa = 2 and IXα = 3; median age = 11.9 years; IQ = 10.9–20.1) who underwent a dual-energy X-ray absorptiometry (DXA). Osteocalcin (OC, n = 18), procollagen type 1 N-terminal propeptide (P1NP, n = 19), collagen type 1 C-terminal telopeptide (CTX, n = 18) and 25-OH Vitamin D (n = 23) were also measured. The participants completed a 3-day food diary (n = 20). Low BMD was defined as a Z-score ≤ −2.0. All participants were receiving uncooked cornstarch (median dosage = 6.3 g/kg/day) at inclusion, and 11 (47.8%) presented good metabolic control. Three (13%) patients (GSD Ia = 1, with poor metabolic control; IIIa = 2, both with high CPK levels) had a BMD ≤ −2.0. CTX, OC and P1NP correlated negatively with body weight and age. 25-OH Vitamin D concentration was decreased in seven (30.4%) patients. Our data suggest that patients with hepatic GSDs may have low BMD, especially in the presence of muscular involvement and poor metabolic control. Systematic nutritional monitoring of these patients is essential. Full article

(1) Background: Glycogen storage disease (GSD) represents a group of twenty-three types of metabolic disorders which damage the capacity of body to store glucose classified basing on the enzyme deficiency involved. Affected patients could present some oro-facial alterations: the purpose of this review is to catalog and characterize oral manifestations in these patients. (2) Methods: a systematic review of the literature among different search engines using PICOS criteria has been performed. The studies were included with the following criteria: tissues and anatomical structures of the oral cavity in humans, published in English, and available full text. Review articles and paper published before 1990 were excluded. (3) Results: 757 articles were identified in the initial search. In the end, 45 articles that met the selection criteria has been analyzed. The information extracted from the articles was classified according to the type of GSD (Ia; Ib; II; III; V; XIV). Oral manifestations range from dental caries to severe periodontitis in paediatric patients, from diffuses and recurrent oral ulcers in the cleft lip and palate. (4) Conclusions: Although considered a rare disease, GSD can present a varied number of oral manifestations. Therefore, it is of great importance for the oral medicine specialist to know and classify them. Full article

A life-long dietary intervention can affect the substrates’ availability for gut fermentation in metabolic diseases such as the glycogen-storage diseases (GSD). Besides drug consumption, the main treatment of types GSD-Ia and Ib to prevent metabolic complications is a specific diet with definite nutrient intakes. In order to evaluate how deeply this dietary treatment affects gut bacteria, we compared the gut microbiota of nine GSD-I subjects and 12 healthy controls (HC) through 16S rRNA gene sequencing; we assessed their dietary intake and nutrients, their microbial short chain fatty acids (SCFAs) via gas chromatography and their hematic values. Both alpha-diversity and phylogenetic analysis revealed a significant biodiversity reduction in the GSD group compared to the HC group, and highlighted profound differences of their gut microbiota. GSD subjects were characterized by an increase in the relative abundance of Enterobacteriaceae and Veillonellaceae families, while the beneficial genera Faecalibacterium and Oscillospira were significantly reduced. SCFA quantification revealed a significant increase of fecal acetate and propionate in GSD subjects, but with a beneficial role probably reduced due to unbalanced bacterial interactions; nutritional values correlated to bacterial genera were significantly different between experimental groups, with nearly opposite cohort trends. Full article