Hereditary Metabolic Disorders Research Articles

Cardiopulmonary determinants of reduced exercise tolerance in Fabry disease.

Fabry disease (FD), also known as Anderson-Fabry disease, is a hereditary disorder of glycosphingolipid metabolism, caused by a deficiency of the lysosomal alpha-galactosidase A enzyme. This causes a progressive accumulation of glycosphingolipids in tissues and organs which represents the main pathogenetic mechanism of FD. The disease is progressive and multisystemic and is characterized by early symptoms and late complications (renal, cardiac and neurological dysfunction). Fatigue and exercise intolerance are early common symptoms in FD patients but the specific causes are still to be defined. In this narrative review, we deal with the contribution of cardiac and pulmonary dysfunctions in determining fatigue and exercise intolerance in FD patients.

I123-FP-CIT (DaTSCAN) SPECT beyond the Most Common Causes of Parkinsonism: A Systematic Review.

As the diagnosis of Parkinson's disease (PD) is fundamentally clinical, the usefulness of ioflupane (123I) single-photon emission computed tomography (SPECT) or DaTSCAN as a diagnostic tool has been a matter of debate for years. The performance of DaTSCAN is generally recommended in the follow-up of patients with a clinically uncertain diagnosis, especially in those with a suspected essential tremor, drug-induced parkinsonism, or vascular parkinsonism. However, there is a dearth of DaTSCAN findings regarding neurodegenerative parkinsonisms besides PD and atypical parkinsonisms. To date, a specific nigrostriatal dopamine uptake pattern that would help differentiate PD from the most frequent atypical parkinsonisms is yet to be described. This fact is further complicated by the possible visualization of abnormalities in the uptake pattern in patients with rarer neurodegenerative parkinsonisms. We aimed to summarize the current literature regarding DaTSCAN findings in patients with rare neurodegenerative parkinsonisms. The PubMed database was systematically screened for studies in English or Spanish up to October 15, 2023, using search terms "DaTSCAN", "ioflupane", "DaT-SPECT", "123I-FP-CIT SPECT", "dopamine transporter imaging", and "[123I] FP-CIT SPECT". Duplicated publications and studies regarding PD, atypical parkinsonisms, dystonia-parkinsonism, essential tremor, and parkinsonism due to non-degenerative causes were excluded. The obtained results were reviewed and summarized, including DaTSCAN findings in fragile X-associated tremor/ataxia syndrome, prion diseases, Huntington's disease, spinocerebellar ataxia, hereditary spastic paraparesis, metabolic disorders, and other diseases (anti-IgLON5 disease, ring chromosome 20 syndrome, chorea-acanthocytosis, and neuronal ceroid lipofuscinosis). This review highlights the need to determine in the future the utility and cost-effectiveness of DaTSCAN, both as a diagnostic and a prognostic tool, in patients with parkinsonian symptoms in rare neurodegenerative diseases.

SEPSIS-LIKE СИНДРОМ У НОВОРОЖДЕННОГО РЕБЕНКА ПРИ НАРУШЕНИИ ЦИКЛА ОБРАЗОВАНИЯ МОЧЕВИНЫ

Sepsis-like syndrome is a septic–like syndrome. The pathogenesis of Sepsis-like syndrome is based on the hyperproduction of proinflammatory cytokines. Hereditary metabolic disorders, including in violation of the urea formation cycle, can occur with the clinic of Sepsis-like syndrome. Ammonium easily penetrates the blood-brain barrier, causes neurotoxic effects, damages glial cells, increases osmolarity, which leads to cerebral edema. The symptoms are similar to hypoxic-ischemic lesions of the central nervous system, meningoencephalitis, intrauterine infections, which leads to a differential diagnostic search for causes and the need to exclude an infectious disease. The article presents a clinical case of a newborn with a Sepsis-like syndrome clinic. The girl was born from 2 births naturally at the age of 38 weeks. In the first day of life, there were signs of respiratory failure. She was on mixed feeding. From the 5th day of life, the deterioration of the condition caused by the syndrome of central nervous system depression, with an increase in depression of consciousness up to coma, the development of seizures. Differential diagnosis was performed with intrauterine infections, sepsis, as there was leukocytosis in the blood, increased ESR, ferritin, procalcitonin, and seeding from the cerebrospinal fluid of Micoplasma hominis. The presence of low urea content in the blood serum, up to its absence, made it possible to suspect hereditary metabolic diseases with a violation in the urea cycle. The conducted examinations revealed a total increase in the concentration of amino acids in the blood using the method of tandem mass spectrometry, metabolites in urine and hyperammonemia up to 354 mcg/dl. The newborn received antibacterial therapy, anticonvulsant therapy, sodium benzoate, and was transferred to a specialized therapeutic mixture "Nutrigen". Despite the therapy, neurological symptoms increased and the girl died at the age of 3 months. This clinical case showed the difficulties of differentiation. diagnosis of causes in the presence of Sepsis-like syndrome in newborn children.

Wilson’s Disease- A Child with An Atypical Presentation

Wilson’s disease is a hereditary disorder of copper metabolism which leads to copper overload in different tissues of the body. Clinical presentation of Wilson disease can vary widely; therefore, diagnosis is not always straightforward. Here we report a 13-year-old girl presented with diffuse persistent stabbing pain in the abdomen, jaundice & dark urine. She had no history of unconsciousness, convulsion, deterioration of school performance, or alteration of sleep pattern. On examination, she was ill-looking, pale, and icteric. The liver was enlarged. Higher psychic Function was intact, with no neurological deficit. A slit-lamp examination by an ophthalmologist promptly revealed the presence of a “Kayser Fleischer Ring” in both eyes. On investigation, hemoglobin was 5.73g/dl, Total bilirubin-37.82mg/dl, ALT-50 IU, AST-95 IU, PT/INR-3.20, serum ceruloplasmin 21mg/dl. Twenty-four hours of urinary copper excretion after penicillamine challenge was 8784 μg/24 hours. We diagnosed the case as Wilson’s disease. This case report aims to share our experience regarding the clinical presentation and diagnosis of Wilson’s disease in a child where Kayser–Fleischer rings in eyes appeared before neurological manifestation occurs and normal serum ceruloplasmin which often creates a diagnostic dilemma.

Brain function in classic galactosemia, a galactosemia network (GalNet) members review.

Classic galactosemia (CG, OMIM #230400, ORPHA: 79,239) is a hereditary disorder of galactose metabolism that, despite treatment with galactose restriction, affects brain function in 85% of the patients. Problems with cognitive function, neuropsychological/social emotional difficulties, neurological symptoms, and abnormalities in neuroimaging and electrophysiological assessments are frequently reported in this group of patients, with an enormous individual variability. In this review, we describe the role of impaired galactose metabolism on brain dysfunction based on state of the art knowledge. Several proposed disease mechanisms are discussed, as well as the time of damage and potential treatment options. Furthermore, we combine data from longitudinal, cross-sectional and retrospective studies with the observations of specialist teams treating this disease to depict the brain disease course over time. Based on current data and insights, the majority of patients do not exhibit cognitive decline. A subset of patients, often with early onset cerebral and cerebellar volume loss, can nevertheless experience neurological worsening. While a large number of patients with CG suffer from anxiety and depression, the increased complaints about memory loss, anxiety and depression at an older age are likely multifactorial in origin.

Long-term monitoring of fatty acid oxidation defects: results from a MetabERN survey.

Implementation of long-chain fatty acid oxidation defects (LCFAOD) in newborn screening (NBS) programs allows for pre-symptomatic diagnosis and treatment. The long-term natural history of NBS LCFAOD patients is largely unknown and may differ from clinically diagnosed pre-NBS patients. This complicates long-term monitoring of LCFAOD and may cause high monitoring variability. To gain insight in current clinical practice, we performed a web-based questionnaire among all metabolic members of the European Reference Network for Hereditary Metabolic Disorders (MetabERN). Thirty-seven colleagues representing at least 35 European metabolic centres shared their experience and results were discussed at the European Metabolic Group (EMG) meeting 2022. The centres concurred in many aspects of long-term monitoring of LCFAOD including the frequency of clinical visits, determination of laboratory parameters, cardiac monitoring and retinopathy screening. Main discrepancies comprised hepatic imaging, glucose monitoring and electrophysiological investigations. Discrepancies may reflect differences in local availability of monitoring tools, the inclusion of LCFAOD in NBS programs as well as differences in local genotypes and phenotypes. Because monitoring strategies are largely based on the natural disease course of clinically identified patients, there might be over-monitoring of some NBS patients. Nevertheless, we advocate long-term monitoring because resulting information is essential to further characterize the natural disease course, develop evidence-based guidelines and provide a basis for evaluation of future therapies.

Selective screening for inborn errors of metabolism using tandem mass spectrometry in West Kazakhstan children: study protocol.

To set the reference values of 51 metabolites in the child population, 750 healthy children will be included. The selective screening will be performed among 1,500 patients aged 1day to 18years with suspected hereditary metabolic disorders. The results of selective screening will be interpreted by comparison with the reference values established. Diagnosis will be based on clinical signs, blood levels of amino acids, acylcarnitines, succinylacetone, and urine levels of organic acids and tests for gene mutations. An assessment of 37 inborn errors of metabolism frequencies in high-risk children will be performed. The research will further develop the national as selective as expanded newborn screening programs. The study was registered in clinicaltrials. gov (https://www. gov/study/NCT05910151) on 16 June 2023.

Primary hyperoxaluria type1-arare hereditary metabolic disorder as cause of livedo racemosa

Livedo racemosa is characterized by abizarrely configurated lightning figure-like appearance with striated to reticulated, livid erythematous macules and results from areduced perfusion of the respective skin area, which can have different underlying pathophysiologies. Arare but relevant cause, especially in young patients with end-stage kidney failure, is primary hyperoxaluria type1 (PH1), ahereditary metabolic disorder in which oxalate accumulates in the body.

Selective Screening for Inborn Errors of Metabolism Using Tandem Mass Spectrometry in Newborns of the West Kazakhstan: Pilot Study

Tandem mass spectrometry can detect and quantify many metabolites in a single blood spot to diagnose amino acid disorders, organic acids, fatty acid oxidation, and urea cycle disorders. The use of tandem mass spectrometry (MS/MS) is expanding for the implementation of newborn screening programs for inborn errors of metabolism and for selective screening of children of different ages. In Kazakhstan, the use of MS/MS in metabolic screening programs is not yet developed due to the high cost of equipment and consumables and the lack of special screening centers and specialists. Data on the prevalence of most inborn errors of metabolism in Kazakhstan are not presented in the literature. Aim: to perform selective screening for hereditary metabolic diseases among newborns in western Kazakhstan using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Methods: Selective screening was performed among 250 newborns with suspected hereditary metabolic disorders using tandem mass spectrometry. Results: The results of selective newborn screening were interpreted by comparison with reference values established for this group. Diagnosis was based on clinical signs, blood levels of amino acids, acylcarnitines, succinylacetone, urine organic acids, and gene mutation tests. An assessment of 37 inborn errors of metabolism frequencies in high-risk newborns was performed. Conclusion: The research will further develop the national as selective as expanded newborn screening programs.

Detection of homogentisic acid by electrospray ionization mass spectrometry.

Homogentisic acid (HGA) is excreted in excessive amounts in the urine of patients with alkaptonuria, which is a hereditary metabolic disorder of phenylalanine and tyrosine. Therefore, the detection of HGA in urine is useful for the diagnosis of alkaptonuria. To evaluate the detection of HGA, we confirmed the color shift of HGA solutions and analyzed them by electrospray ionization mass spectrometry (ESI-MS). We observed the color change of the HGA solutions under different pH conditions (pH 6.0, 7.0, and 8.0) and examined the influences of adding potassium hydroxide (KOH) and ascorbic acid (AA) to the HGA solutions. Then, we analyzed the chemical reaction in HGA solutions using ESI-MS. The HGA solution at pH 8.0 became brown after incubation at room temperature for 24 h and became darker brown with the addition of KOH; however, HGA solutions at pH 6.0 and 7.0 showed no color changes. The brown color change of the HGA solution at pH 8.0 was also inhibited by AA. Moreover, all HGA sample solutions showed the deprotonated molecular ion peak at m/z 167.035 in the negative ion mode after incubation at room temperature for 24 h and with the addition of KOH and AA. We identified the molecular ion of HGA in all sample solutions by ESI-MS, regardless of different pH conditions, color changes, or the presence of AA. These results suggest that spectral analysis by ESI-MS is suitable for the detection of HGA and the diagnosis of alkaptonuria.

Update of expert recommendations on Wilson’s disease management

Wilson's disease is a rare autosomal recessive hereditary disorder of copper metabolism characterized by excessive copper build up in tissues, including brain and liver. The genetic defect localized at the 13q14 – q21 locus affects the gene for copper transporting protein ATP7B in the liver. This defect can be caused by deletions, insertions or missense mutations, leading to disruption of the copper incorporation into ceruloplasmin and the excretion of excess copper into bile. The disease is characterized by liver damage, neuropsychiatric symptoms, musculoskeletal, hematological and renal clinical signs, the presence of Kayser-Fleischer rings as well as many other possible symptoms, with their manifestation depending on the timeliness of diagnosis, stage and form of the disease, and therapeutic interventions.Organizations investigating the problems of Wilson's disease regularly issue new recommendations as knowledge about the disease expands. Innovative diagnostic and therapeutic procedures are put into practice, and views on the course of the disease features change. The general updates of the latest international recommendations described in this article for their early introduction into practical healthcare relate to diagnostic algorithms, indications and the choice of timing and methods of drug treatment in various groups of patients with Wilson's disease, including a more complete review of neuropsychiatric care, as well as the possible tools for therapy monitoring.

Rare Cause of Liver Cell Failure in Infants: Wolman Disease

Wolman disease is an extremely rare hereditary metabolic lipid storage disorder, characterized by a total deficiency of lysosomal acid lipase (LAL), which leads to the accumulation of cholesteryl esters and triglycerides in the lysosomes, resulting in more or less progressive damage to numerous organs, thus presenting the patient with vomiting, diarrhea, and severe malnutrition. With a fatal outcome in the first months of life if untreated. We present the case of a two-month-old infant admitted for abdominal distension; physical examination revealed jaundice, hepatomegaly, and splenomegaly; biological investigations revealed hepatic cytolysis, anemia, and thrombocytopenia. Imaging studies showed bilateral calcifications of the adrenal glands. The diagnosis of Wolman disease was confirmed by measuring the activity of the collapsed lysosomal acid lipase.

Lipoprotein (a) as a marker of hereditary lipid metabolism disorders in patients with early manifestation of coronary artery disease

Background: The clinical phenotype of familial hypercholesterolemia (FH) combined with the classical genetic defects of this disease increase the risk of coronary artery disease (CAD) in the case of a high level of lipoprotein (a) (Lp(a)). Aim: To assess the association of hereditary disorders of lipid metabolism with a high level of Lp(a) in the case of an early manifestation of CAD in the absence of the FH phenotype. Methods: We studied 81 patients with premature CAD (at the age up to 55 years in men and up to 60 years in women). Lp(a) was measured in the blood serum by the immunoturbidimetric method. We performed the molecular genetic testing, using massively parallel sequencing, which included the following panel of genes: ABCA1, ABCG1, ABCG5, ABCG8, ANGPTL3, APOA1, APOA2, APOA4, APOA5, APOB, APOC1, APOC2, APOC3, APOE, APOH, CETP, CH25H, CIDEC, CREB3L3, GPD1, GPIHBP1, LCAT, LDLR, LDLRAP1, LIPA, LIPC, LIPE, LIPG, LMF1, LPA, LPL, MTTP, MYLIP, NPC1, NPC1L1, NPC2, PCSK9, PLTP, PPP1R17, SAR1B, SCARB1, STAP1. Results: 24 (29.6%) patients had Lp(a) 30 mg/dl and were more likely to have a family history of CAD (70.8% vs 42.1%, p=0.05). In patients with a confirmed FH phenotype, there were no pathogenic variants associated with hereditary disorders of lipid metabolism. 4 patients with Lp(a) 30 mg/dl without a confirmed FH phenotype appeared to be carriers of pathogenic variants in the genes of lipid metabolism (LDLR p.Glu763Asp, ABCA1 p.Arg1128His, APOA5 p.His321Le), as well as of a not previously registered variant in the LIPE gene NM_005357.4:c. 2312TC. Conclusions: Lp(a) can be an appropriate marker for revealing pathogenic variants in the genes of the lipid metabolism system in patients without the clinical FH phenotype with an early CAD manifestation.

Treatment of maple syrup urine disease: Benefits, risks, and challenges of liver transplantation.

Maple syrup urine disease (MSUD) is caused by a deficiency in the activity of the branched-chain α-ketoacid dehydrogenase (BCKD) complex, promoting the accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine, as well as their respective α-keto acids. MSUD is an autosomal recessive hereditary metabolic disorder characterized by ketoacidosis, ataxia, coma, and mental and psychomotor retardation. The mechanisms involved in the brain damage caused by MSUD are not fully understood. Early diagnosis and treatment, as well as proper control of metabolic decompensation crises, are crucial for patients' survival and for a better prognosis. The recommended treatment consists of a high-calorie diet with restricted protein intake and specific formulas containing essential amino acids, except those accumulated in MSUD. This treatment will be maintained throughout life, being adjusted according to the patients' nutritional needs and BCAA concentration. Because dietary treatment may not be sufficient to prevent neurological damage in MSUD patients, other therapeutic strategies have been studied, including liver transplantation. With transplantation, it is possible to obtain an increase of about 10% of the normal BCKD in the body, an amount sufficient to maintain amino acid homeostasis and reduce metabolic decompensation crises. However, the experience related to this practice is very limited when considering the shortage of liver for transplantation and the risks related to the surgical procedure and immunosuppression. Thus, the purpose of this review is to survey the benefits, risks, and challenges of liver transplantation in the treatment of MSUD.

Medical care of patients with Wilson disease in Germany: a multidisciplinary survey among university centers

BackgroundWilson disease (WD) is a rare, hereditary disorder of copper metabolism. Due to its variable symptoms and manifestations, diagnosis remains challenging. Affected patients must obtain lifelong medical treatment, as the disease is fatal if untreated. Patients require continuous monitoring, but little is known about the care of these patients in Germany. Therefore, we analyzed the medical care of WD patients at German university centers. We sent a questionnaire containing 20 questions to a total of 108 departments of pediatrics, neurology and gastroenterology in 36 university hospitals. Our questions referred to the characteristics of WD patients at the different sites and internal procedures regarding diagnosis, therapy and follow-up. A descriptive statistical analysis was performed.ResultsSixty-three departments (58%) returned our questionnaire. In total, approximately one-third of the estimated WD patients in Germany are seen annually in the outpatient clinics of these departments (approx. 950 patients). There are only a few departments which treat patients in a multidisciplinary setting (12%). Our survey revealed that for diagnosis, 51% of all departments used an algorithm based on the Leipzig score as recommended by international guidelines. Most departments apply essential parameters recommended by WD guidelines. Routine monitoring is performed at least biannually by 84% of the departments, and standard investigations for monitoring are regularly applied. A routine family screening is performed by 84% of all departments. A reduction in medical therapy during pregnancy is recommended by 46% of the departments. Only 14% suggested that WD patients should not breastfeed. Liver transplantation (LT) due to WD is a rare but repeatedly occurring event. Most departments of gastroenterology (72%) reported at least one patient with LT within the last decade.ConclusionsMedical care of WD patients at German university centers follows the recommendations set forth by international guidelines, but only a few centers treat significant numbers of patients. The surveillance of patients does not follow specified standards, but most departments adhere to the accepted guidelines. The formation of central units and networks in a multidisciplinary setting should be evaluated to improve the care of WD patients.

The deleterious variants of N-acetylgalactosamine-6-sulfatase (GalN6S) enzyme trigger Morquio a syndrome by disrupting protein foldings

Lysosomal enzymes degrade cellular macromolecules, while their inactivation causes human hereditary metabolic disorders. Mucopolysaccharidosis IVA (MPS IVA; Moquio A syndrome) is one of the lysosomal storage disorders caused by a defective Galactosamine-6-sulfatase (GalN6S) enzyme. In several populations, disease incidence is elevated due to missense mutations brought on by non-synonymous allelic variation in the GalN6S enzyme. Here, we studied the effect of non-synonymous single nucleotide polymorphism (nsSNPs) on the structural dynamics of the GalN6S enzyme and its binding with N-acetylgalactosamine (GalNAc) using all-atom molecular dynamics simulation and an essential dynamics approach. Consequently, in this study, we have identified three functionally disruptive mutations in domain-I and domain-II, that is, S80L, R90W, and S162F, which presumably contribute to post-translational modifications. The study delineated that both domains work cooperatively, and alteration in domain II (S80L, R90W) leads to conformational changes in the catalytic site in domain-I, while mutation S162F mainly provokes higher residual flexibility of domain II. These results show that these mutations impair the hydrophobic core, implying that Morquio A syndrome is caused by misfolding of the GalN6S enzyme. The results also show the instability of the GalN6S-GalNAc complex upon substitution. Overall, the structural dynamics resulting from point mutations give the molecular rationale for Moquio A syndrome and, more importantly, the Mucopolysaccharidoses (MPS) family of diseases, re-establishing MPS IVA as a protein-folding disease. Communicated by Ramaswamy H. Sarma

A Systematic Review and Meta-Analysis of the R778L Mutation in ATP7B With Wilson Disease in China

BackgroundWilson disease (WD) is a hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene. There are more than 1000 pathogenic variants identified in ATP7B. R778L is the most common ATP7B mutation in China. MethodsTo estimate whether R778L is associated with the onset age of WD and other clinical variables. Genotyping results of ATP7B gene were collected in our 22 patients with WD. We then conducted a systematic review and meta-analysis in databases, using the keywords Wilson disease and R778L mutation. ResultsAfter the screening, a total of 23 studies were included, including 3007 patients with WD. Patients with R778L mutation presented at an earlier age (standardized mean difference [SMD] = −0.18 [95% confidence interval, −0.28 to 0.08], P = 0.0004) and had lower ceruloplasmin concentration (SMD = −0.21 [95% confidence interval, −0.40 to −0.02], P = 0.03) than the patients without the R778L mutation. However, sex (odds ratio [OR] = 1.07 [95% confidence interval, 0.89 to 1.29], P = 0.32) and first presentation were not associated with R778L mutation in WD (hepatic: OR = 1.37 [95% confidence interval, 0.87 to 2.16, P = 0.17; neurological: OR = 0.79 [95% confidence interval, 0.48 to 1.30, P = 0.35; mix: OR = 1.04 [95% confidence interval, 0.42 to 2.53, P = 0.87; asymptomatic/others: OR = 1.98 [95% confidence interval, 0.49 to 7.96, P = 0.34). ConclusionsOur results indicated that the R778L mutation is associated with an earlier presentation and lower ceruloplasmin concentration in China.

Wilson-Konovalov Disease: Literature Review and Case Study

Wilson-Konovalov disease (hepatolenticular degeneration) is a heavy potentially treatable hereditary disorder of copper metabolism, which is characterized by pathological accumulation of copper. The disease is caused by mutations in ATPase copper transporting beta polypeptide (ATP7B), which encodes the transmembrane ATPase transporting copper, which leads to a violation of copper homeostasis and copper overload in the liver, brain and other organs. The clinical course may vary by type and severity of symptoms, but progressive liver disease is a common feature. Patients may also suffer from neurological disorders and mental symptoms. Hepatolenticular degeneration is diagnosed using diagnostic algorithms that include clinical symptoms and signs, indicators of copper metabolism and ATP7B DNA analysis. Available treatments include chelation therapy and zinc salts, which eliminate copper overload by various mechanisms. In addition, liver transplantation is indicated in some cases. With early diagnosis and treatment, the prognosis is good; however, an important issue is the diagnosis of patients before the appearance of serious symptoms. The paper reviews the latest data on Wilson-Konovalov disease with a detailed description of the etiology, pathogenesis, macroscopic and microscopic pictures of the disease, neurological manifestations, diagnosis, differential diagnosis, new treatment methods, prognosis and complications. A clinical case of Wilson — Konovalov disease in a 28-year-old patient with extrapyramidal manifestations is presented.

Echocardiographic Assessment of Patients with Glycogen Storage Disease in a Single Center.

Glycogen storage disease (GSD) is a hereditary metabolic disorder caused by enzyme deficiency resulting in glycogen accumulation in the liver, muscle, heart, or kidney. GSD types II, III, IV, and IX are associated with cardiac involvement. However, cardiac manifestation in other GSD types is unclear. This study aimed to describe whether energy deprivation and the toxic effects of accumulated glycogen affect the heart of patients with GSD. We evaluated the left ventricle (LV) wall mass, LV systolic and diastolic function and myocardial strain with conventional echocardiography and two-dimensional speckle-tracking echocardiography (2D STE) in 62 patients with GSD type I, III, VI and IX who visited the Wonju Severance Hospital in 2021. Among the GSD patients, the echocardiographic parameters of 55 pediatrics were converted into z-scores and analyzed. Of the patients, 43 (62.3%), 7 (11.3%) and 12 (19.4%) patients were diagnosed with GSD type I, type III, and type IX, respectively. The median age was 9 years (range, 1-36 years), with 55 children under 18 years old and seven adults over 18 years. For the 55 pediatric patients, the echocardiographic parameters were converted into a z-score and analyzed. Multiple linear regression analysis showed that the BMI z-score (p = 0.022) and CK (p = 0.020) predicted increased LV mass z-score, regardless of GSD type. There was no difference in the diastolic and systolic functions according to myocardial thickness; however, 2D STE showed a negative correlation with the LV mass (r = -0.28, p = 0.041). Given that patients with GSD tend to be overweight, serial evaluation with echocardiography might be required for all types of GSD.

Lipidomic alterations in human saliva from cystic fibrosis patients

Cystic fibrosis is a hereditary metabolic disorder characterized by impaired traffic of chloride ions and water through membranes of the respiratory and gastrointestinal, that causes inadequate hydration of airway surfaces, dehydrated mucous secretions and a high-sodium chloride sweat. Although the classical presentation of the condition is well known, a better characterization of metabolic alterations related is need. In particular, the metabolic composition alterations of biological fluids may be influence by the disease state and could be captured as putative signature to set targeted therapeutic strategies. A targeted comprehensive mass spectrometry-based platform was employed to dissect the lipid content of saliva samples form CF patients, in order to investigate alterations in the lipid metabolic homeostasis related to the pathology, chronic obstructive pulmonary disease, Pseudomonas Aeruginosa infection, pancreatic insufficiency, liver disfunction and diabetes-related complications.