Deficiency Type Research Articles

Assessment of health state utilities associated with adult and pediatric acid sphingomyelinase deficiency (ASMD)

IntroductionAcid sphingomyelinase deficiency (ASMD) type B is a rare genetic disorder leading to enlargement of the spleen and liver, pulmonary dysfunction, and other symptoms. Cost-utility analyses are often conducted to quantify the value of new treatments, and these analyses require health state utilities. Therefore, the purpose of this study was to estimate utilities associated with varying levels of severity of adult and pediatric ASMD type B.MethodsSeven adult and seven child health state vignettes describing ASMD were developed based on published literature, clinical trial results, and interviews with clinicians, patients with ASMD, and parents of children with ASMD. The health states were valued in time trade-off interviews with adult general population respondents in the UK.ResultsInterviews were completed with 202 participants (50.0% female; mean age = 41.3 years). The health state representing ASMD without impairment had the highest mean utility for both the adult and child health states (0.92/0.94), and severe ASMD had the lowest mean utility (0.33/0.45). Every child health state had a significantly greater utility than the corresponding adult health state. Differences between adult/child paired states ranged from 0.02 to 0.13. Subgroup analyses explored the impact of parenting status on valuation of child health states.DiscussionGreater severity of ASMD was associated with lower mean utility. Results have implications for valuation of pediatric health states. The resulting utilities may be useful in cost-utility modeling estimating the value of treatment for ASMD.

A Gadolinium(III) Complex Based on Pyridoxine Molecule with Single-Ion Magnet and Magnetic Resonance Imaging Properties.

Pyridoxine (pyr) is a versatile molecule that forms part of the family of B vitamins. It is used to treat and prevent vitamin B6 deficiency and certain types of metabolic disorders. Moreover, the pyridoxine molecule has been investigated as a suitable ligand toward metal ions. Nevertheless, the study of the magnetic properties of metal complexes containing lanthanide(III) ions and this biomolecule is unexplored. We have synthesized and characterized a novel pyridoxine-based GdIII complex of formula [GdIII(pyr)2(H2O)4]Cl3 · 2 H2O (1) [pyr = pyridoxine]. 1 crystallizes in the triclinic system and space group Pī. In its crystal packing, cationic [Gd(pyr)2(H2O)4]3+ entities are connected through H-bonding interactions involving non-coordinating water molecules and chloride anions. In addition, Hirshfeld surfaces of 1 were calculated to further investigate their intermolecular interactions in the crystal lattice. Our investigation of the magnetic properties of 1, through ac magnetic susceptibility measurements, reveals the occurrence of a slow relaxation in magnetization in this mononuclear GdIII complex, indicating an unusual single-ion magnet (SIM) behavior for this pseudo-isotropic metal ion at very low temperatures. We also studied the relaxometric properties of 1, as a potential contrast agent for high-field magnetic resonance imaging (MRI), from solutions of 1 prepared in physiological serum (0.0-3.2 mM range) and measured at 3 T on a clinical MRI scanner. The values of relaxivity obtained for 1 are larger than those of some commercial MRI contrast agents based on mononuclear GdIII systems.

Effect of Traditional Chinese Medicine umbilical moxibustion combined with diet nursing in the treatment of diarrhea of spleen and stomach Qi deficiency type in children

Effect of Traditional Chinese Medicine umbilical moxibustion combined with diet nursing in the treatment of diarrhea of spleen and stomach Qi deficiency type in children

Uniparental Disomy as a Mechanism for Combined Oxidative Phosphorylation Deficiency Associated with MRPS34 Gene.

Mitochondrial oxidative phosphorylation (OXPHOS) is a cellular process that generates most of the cellular energy required by the body. Disorders affecting OXPHOS are multisystem diseases caused by pathogenic variants in more than 50 genes. In 2017, biallelic variants in the MRPS34 gene were shown to cause combined oxidative phosphorylation deficiency type 32 (COPD32) (OMIM#617664); however, only 7 patients have been reported in the literature up to this moment. COPD32 is characterized mainly by a severe Leigh-like syndrome. Whole-exome sequencing identified a homozygous pathogenic variant in the MRPS34 gene, c.322-10G>A. Only the mother was heterozygous for this variant. SNP-array analysis was performed, which revealed a region of absence of heterozygosity in variant 16q with 9.8Mb, compatible with maternal uniparental disomy. We report the case of an 18-year-old female with unremarkable family history. The pregnancy was complicated by oligohydramnios, and the neonatal period was unremarkable. She evolved with low weight, mild-moderate developmental delay/intellectual disability, and hypogonadotropic hypogonadism. On examination, she had slender habitus, joint laxity, and kyphoscoliosis. The cardiac evaluation was normal, and the head MRI showed bilateral olivary nucleus degeneration that was not confirmed subsequently. Extensive metabolic studies documented only mild lactate and pyruvate elevation, and the chromosomal microarray was normal. We have reported the case of the first patient with COPD32 due to partial maternal uniparental disomy of chromosome 16, being first in Portugal and seventh in the literature. Contrarily to previous patients, who died in the first months of life or survived with severe DD/ID, and had a Leigh-like syndrome, this case is significantly milder, contributing to a better characterization of the phenotypic spectrum. Recurrence risk is unexpectedly low in this instance. This case illustrates the importance of segregation analysis in patients with homozygous recessive mutations.

Uncovering the Challenges of Rare Diseases: Insights From a Retrospective Cross-Sectional Study in Albania (2005-2022).

Diagnosing and treating rare diseases pose significant challenges within global healthcare systems due to their low prevalence and varying criteria for defining them. In Albania, the absence of a dedicated registry for rare diseases exacerbates these challenges. Recognising this gap, a retrospective cross-sectional study was conducted from January 2005 to December 2022 to analyse the incidence and prevalence of rare haematologic diseases in the country, diagnosed in the Hematology Service at the University Hospital Centre "Mother Teresa," which is the sole diagnostic center for blood diseases in Albania. This study aims to provide insights into the frequency of these diseases within the adult Albanian population and seeks to underscore the critical need for improved data collection and research in this field of healthcare. The primary objective of this study is to assess the incidence and prevalence of rare hematologic diseases diagnosed at the Hematology Service of the University Hospital Centre "Mother Teresa" in Albania from January 2005 to December 2022. This retrospective cross-sectional study employed a descriptive study design, focusing on the analysis of rare hematologicdisease incidence and prevalence. The study was conducted exclusively at the University Hospital Centre "Mother Teresa" in Albania, the primary diagnostic center for blood-related disorders in the country. Data collection spanned a period of 18 years, from January 2005 to December 2022, encompassing patient records. Inclusion criteria encompassed adult patients aged 15 years and older who had received diagnoses of rare hematologic diseases during the specified timeframe, without specific operational definitions applied. Non-probability convenience sampling was used, including all eligible cases identified within the study's timeframe, obviating the need for formal sample size calculation. Data were extracted from the records of the Hematology Service at the University Hospital Centre "Mother Teresa," primarily using medical records containing essential patientinformation. Data analysis utilised software such as EXCEL 16.0 and SPSS (v. 25.0), applying descriptive statistical methods, including frequencies and percentages, to assess the incidence and prevalence of rare hematologic diseases. The study's findings were summarised and presented in a tabular format to provide a clear and concise overview of the results. Our study identified 64 cases of rare hematologic diseases among adults. Notably, primary myelofibrosis (MF) exhibited the highest incidence andprevalence rate, followed byWaldenström macroglobulinemia (WM) and Gaucher disease (GD) emerging as the most prevalent diagnoses after MF, with 16 and 10 cases, respectively. Several ultra-rare diseases, such as Fanconi anemia and chronic eosinophilic leukemia, were also detected, indicating a significant disease burden, while diseases such as Factor X deficiency and Niemann-Pick disease type C were exceptionally rare. Diagnosing and treating rare diseases remain formidable challenges in healthcare systems worldwide. This study underscores the need for enhanced awareness, research, and thepressing need for dedicated registries, collaborative research initiatives, and heightened attention to these conditions to enhance our understanding and management of rare hematological diseases, particularly within the Albanian healthcare context.

SUPERhip Reconstruction Treatment in Patients with Congenital Femoral Deficiency of Paley's Classification Type 1b.

Congenital femoral deficiency (CFD) is a challenging and complex condition that causes limb lengthening. We focused on the clinical and radiographic results of SUPERhip procedures in patients with congenital femoral deficiency type 1b, according to Paley's classification, prior to femoral lengthening. We reviewed all records and radiographs of patients who underwent this procedure between 2005 and 2020. We included 26 patients, with clinical and radiographic assessments performed during pre- and post-operative evaluations. There were twenty-six patients (15 right vs. 11 left), with a mean age of 7 years (1-18). Most of the patients were female (17 patients; 65.4%). Twenty (76.9%) patients were undergoing their first procedure and six (23.1%) had already undergone a previous surgery. There was a significant improvement in all radiographic parameters, with the mean preoperative and postoperative Neck-Shaft Angle (NSA) being 72.3 ± 7.1° vs. 133.1 ± 12.7°, the Center-Edge Angle (CEA) 16.8 ± 9.8° vs. 33.5 ± 14.1°, and the Acetabular Index (AI) 27.8 ± 6.9° vs. 16.4 ± 6.8°, respectively. The complication rate was 15.4%, predominantly affecting patients under 5 years old. The SUPERhip procedure is an effective and reproducible technique for clinical and radiographic correction to a significant degree in patients with Paley's type 1b CFD, in preparation for bone lengthening surgery.

Adult-onset combined oxidative phosphorylation deficiency type 14 manifests as epileptic status: a new phenotype and literature review

BackgroundCombined oxidative phosphorylation deficiency (COXPD) is a severe disorder with early onset and autosomal recessive inheritance, and has been divided into 51 types (COXPD1–COXPD51). COXPD14 is caused by a mutation in the FARS2 gene, which encodes mitochondrial phenylalanyl-tRNA synthetase (mt-PheRS), an enzyme that transfers phenylalanine to its cognate tRNA in mitochondria. Since the first case was reported in 2012, an increasing number of FARS2 variations have been subsequently identified, which present three main phenotypic manifestations: early onset epileptic encephalopathy, hereditary spastic paraplegia, and juvenile-onset epilepsy. To our knowledge, no adult cases have been reported in the literature.MethodsWe report in detail a case of genetically confirmed COXPD14 and review the relevant literature.ResultsApproximately 58 subjects with disease-causing variants of FARS2 have been reported, including 31 cases of early onset epileptic encephalopathy, 16 cases of hereditary spastic paraplegia, 3 cases of juvenile-onset epilepsy, and 8 cases of unknown phenotype. We report a case of autosomal recessive COXPD14 in an adult with status epilepticus as the only manifestation with a good prognosis, which is different from that in neonatal or infant patients reported in the literature. c.467C > T (p.T156M) has been previously reported, while c.119_120del (p.E40Vfs*87) is novel, and, both mutations are pathogenic.ConclusionsThis case of autosomal recessive COXPD14 in an adult only presented as status epilepticus, which is different from the patients reported previously. Our study expands the mutation spectrum of FARS2, and we tended to define the phenotypes based on the clinical manifestation rather than the age of onset.

The limbal stem cell niche in development, insights from mouse models and children with aniridia

Congenital aniridia, a rare eye disease of underdevelopment of the eye, leads to multiple eye abnormalities and pathologies, including a progressive limbal stem cell deficiency leading to the emergence and progression of an aniridia‐associated keratopathy. A deeper understanding of the characteristics of this deficiency could help to explain the observed pattern of progression and may provide insights into future treatments of this, and other types of limbal stem cell deficiency. From imaging studies in infants and young children with aniridia but with clear corneas, early phenotypic changes are apparent at the limbal border, with vascular tissue and inflammation apparent. In the central cornea, elevated inflammation and a nerve deficit are present early in life. In a novel mouse model of aniridia with slow development of keratopathy, limbal stem cell markers are perturbed after birth in clear corneas, and exhibit a characteristic time‐dependent pattern as the onset of clinically visible keratopathy emerges and starts to progress. Changes in the stromal and subbasal corneal nerves are also visible in the model and can provide insights into the neural deficit seen in the human disease. The model is moreover ideal for the evaluation of novel compounds aiming to slow the progression of keratopathy and preserve corneal transparency.

Chlamydomonas dynein-preassembly-deficient mutants exhibit characteristic ciliary responses to viscous media.

Ciliary-dynein preassembly in the cytoplasm is critical for the assembly and movement of motile cilia, organelles that function under viscous conditions. Defects in preassembly often lead to a reduction in specific types of ciliary dyneins. Here, we investigated how environmental viscosity affects the motility of preassembly-deficient cilia in the alga Chlamydomonas. We found that, depending on the type of ciliary dynein deficiency, each Chlamydomonas mutant displays a characteristic phenotype in cell propulsion. Our results highlight not only the unique function(s) of each dynein species, but also the importance of functional coordination between dyneins for ciliary motility under viscous conditions.

Ai Rudi’s Experience of Treating Androgen Alopecia of Spleen Deficiency and Dampness Accumulation Type with Zhaqu Pingwei Powder

Ai Rudi’s Experience of Treating Androgen Alopecia of Spleen Deficiency and Dampness Accumulation Type with Zhaqu Pingwei Powder

中西医结合治疗气虚血瘀型不稳定型心绞痛的研究进展

中西医结合治疗气虚血瘀型不稳定型心绞痛的研究进展

Nursing Experience of Treating a Patient with Spleen Kidney Yang Deficiency Type Hypothyroidism with Huolong Cupping Therapy

Nursing Experience of Treating a Patient with Spleen Kidney Yang Deficiency Type Hypothyroidism with Huolong Cupping Therapy

Rhabdomyolysis in childhood: A case of carnitine palmitoyltransferase deficiency type II

Rhabdomyolysis in childhood: A case of carnitine palmitoyltransferase deficiency type II

TARS2 Variants Cause Combination Oxidative Phosphorylation Deficiency-21: A Case Report and Literature Review.

The aim of the study is to explore the clinical and genetic characteristics of the combined oxidative phosphorylation defect type 21 (COXPD21) caused by the TARS2 compound heterozygous pathogenic variants, and to improve clinicians' awareness of the disease. The proband was a girl of first birth, with repeated refractory hypokalemia, hearing impairment, developmental delay, intellectual disability, developmental retardation after infection, high limb muscle tension, and increased serum lactate as the clinical phenotype. The clinical performance, diagnosis, treatment process, and gene characteristics of COXPD21 caused by TARS2 of the case were analyzed, reviewed, and compared with the literature from the CNKI, Wanfang Data, and biomedical literature database (PubMed) until November 2021. The child was diagnosed with COXPD21 after two heterozygous variants in the TARS2 gene were found via whole exome sequencing. One of the variants was c.1679(exon14) A > C (p.Asp560Ala) missense, derived from the mother, and the other was c.1036(exon10)C > T (p.Arg346Cys) missense, derived from the father. The literature was searched and reviewed with the keywords "mitochondrial encephalomyopathy," "TARS2," and "combination oxidative phosphorylation deficiency type 21." A total of four complete domestic and foreign cases were collected from the literature search. COXPD21 onset by a complex heterozygous variant of TARS2 causes refractory hypokalemia, which is rarely reported in China and abroad.

Diet-Related Anemias: A Comprehensive Review on Types, Causes, Diagnosis, and Treatment

Background: Anemia, a prevalent blood disorder characterized by reduced red blood cells or hemoglobin, has diverse etiologies related to nutritional deficiencies, notably iron, vitamin B12, and B9. Its impact on quality of life is especially significant in elderly individuals and those with chronic conditions. Objective: This systematic review aims to collate and synthesize the current literature on nutrient-related anemias, focusing on types, pathophysiology, diagnosis, and treatment. Methods: A thorough search was conducted in databases including Google Scholar, PubMed, and Research Gate using keywords such as "anemia," "types," "pathophysiology," "diagnosis," and "treatment." The review encompasses studies that detail the prevalence, causes, symptoms, risk factors, diagnostic methods, and treatment options for anemias related to iron, vitamin B12, and B9 deficiencies. Results: The review found that anemia affects approximately 24.8% of the global population, with higher prevalence rates in vulnerable groups such as infants, children, and pregnant women. Iron deficiency anemia, the primary form globally, is prevalent in various populations due to factors like poverty, malnutrition, and gastrointestinal conditions. Diagnostic approaches include both traditional laboratory tests and newer metabolite tests like homocysteine and methylmalonic acid. Treatment strategies vary based on the type of deficiency and include oral and intramuscular supplements, with intravenous iron for malabsorption cases and folic acid for folate deficiency. Conclusion: Early detection and effective treatment of diet-related anemias are crucial to prevent serious complications and mitigate their impact on quality of life. The review highlights the importance of tailored treatment approaches, including dietary changes, supplements, and medications, to address the specific needs of individuals with different types of anemia.

Mucormycosis of the Mandible and Tongue: A Systematic Scoping Review

Mucormycosis is a rare human infection associated with Mucorales, a group of filamentous moulds found in different environmental niches. Its oral manifestations may occur in the mandible and tongue despite being rare. We aimed to systematically review the data on clinical manifestations, risk factors, diagnostic approaches, treatment options, and outcomes of mandibular and tongue mucormycosis. An electronic search of articles published between January 1975 and November 2022 in PubMed, Web of Science, and EMBASE databases was performed. A total of 22 articles met the inclusion criteria and reported 27 cases of oral mucormycosis in total. Fourteen patients had mandibular mucormycosis signs unrelated to COVID-19 infection, 6 had SARS-CoV-2-related mandibular mucormycosis, and 6 had manifestations in the tongue. All published case reports during the COVID-19 pandemic were from India. Patient ages ranged from 4 months old to 82 years, and most patients had important comorbidities, such as blood dyscrasias related to immune deficiency and uncontrolled type 2 diabetes mellitus. The signs and symptoms of mandibular and tongue mucormycosis varied from dental pain, loose teeth, and nonhealing sockets to dysphagia and paraesthesia of the lip. Some patients also reported trismus, draining sinus tract, and facial pain. The diagnosis of oral mucormycosis was based on a combination of clinical, radiographic, and histopathologic findings by demonstrating fungal hyphae in tissue specimens. In most cases, mucormycosis was managed with systemic amphotericin B, strict glycaemic control, and aggressive surgical debridement of infected tissue, minimising the progression of the fungal infection and thus improving the survival rate. In some cases, combined antifungal therapy, antibiotic therapy, and chlorhexidine mouthwashes were used successfully. Recognition of the signs and symptoms by oral care providers is pertinent for the early diagnosis and treatment of tongue and mandibular mucormycosis, and providers should be aware of the possibility of this opportunistic fungal infection in patients with COVID-19. A multidisciplinary approach is recommended for the management of this lethal infection.

The effects of Danzhi Jiangtang capsule on clinical indices and vascular endothelial function in patients with impaired glucose tolerance of Qi–Yin deficiency type

Objective To observe the effect of Danzhi Jiangtang capsule (DJC) on the clinical indexes and vascular endothelial function indexes in patients with impaired glucose tolerance (IGT). Methods A total of 106 patients were enrolled and randomly assigned to the treatment group and control group following a four-week washout period. The patients in the control group received a general lifestyle intervention, while those in the treatment group received DJC (2.0 g 3× a day) in conjunction with the intervention given to the control group patients. The physiological and biochemical levels, vascular endothelial function indices, and traditional Chinese medicine (TCM) syndrome ratings of the patients in the two groups were compared after 12 weeks of therapy. Results In the control group, the diastolic blood pressure (DBP) was significantly improved compared with those before treatment (83.31 ± 6.47 vs. 79.21 ± 6.17, p < .01) (CI: 1.45, 6.73; Cohen’s d: 10.51), as was the case with the nitric oxide (NO) levels and TCM syndrome points (35.71 ± 4.58 vs. 43.96 ± 5.17, 9.57 ± 2.63 vs. 5.38 ± 1.79, p < .001) (CI: –10.28, –6.24; 3.12, 5.18; Cohen’s d: 0.90). In the treatment group, the levels of fasting blood glucose, endothelin and vascular endothelial growth factor were significantly improved compared with control group (4.92 ± 0.21 vs. 5.59 ± 0.31, 59.37 ± 13.25 vs. 72.13 ± 12.37, 19.25 ± 2.80 vs. 26.76 ± 1.88, p < .001) (CI: 0.55, 0.78; 7.40, 18.13; 6.52, 8.50; Cohen’s d: 4.94, 0.41, 1.32), as was the case with 2-h post-load plasma glucose and total cholesterol (TC) (8.33 ± 0.62 vs. 8.89 ± 1.55, 4.61 ± 1.05 vs. 5.22 ± 1.12, p < .05) (CI: 0.07, 1.07; 0.15, 1.06; Cohen’s d: 0.40, 0.51). Conclusions Treatment with DJC could significantly improve the physiological and biochemical indicators, vascular endothelial function, and TCM syndrome points of IGT patients, indicating that DJC could be a potential drug to treat patients with IGT of Qi–Yin deficiency type.

Clinical characteristics and genetic analysis of two children with Familial glucocorticoid deficiency type 1 due to variants of MC2R gene

To improve the recognition of Familial glucocorticoid deficiency type 1 (FGD1) due to variants of melanocortin 2 receptor (MC2R) gene. Two children with FGD1 diagnosed at the Henan Children's Hospital respectively in 2019 and 2021 were selected as the study subjects. Clinical data, treatment, follow-up and results of genetic testing were collected and retrospectively analyzed. Whole exome sequencing revealed that both children had harbored compound heterozygous variants of the MC2R gene, including c.433C>T (p.R145C) and c.710T>C (p.L237P) in child 1, and c.145delG (p.V49Cfs*35) and c.307G>A (p.D103N) in child 2, among which c.710T>C (p.L237P) and c.145delG (p.V49Cfs*35) were unreported previously. FGD1 is clinically rare, and genetic sequencing is crucial for the definite diagnosis. Discovery of the and novel variants has enriched the mutational spectrum of the FGD1 gene.

A data-driven Bayesian model for evaluating the duration of detention of ships in PSC inspections

Port State Control (PSC) inspections are essential for port authorities to improve vessel quality and ensure maritime safety worldwide. However, the increasing frequency and duration of ship detentions indicate serious deficiencies of visiting vessels still largely exist, highlighting the urgent need for scientific solutions. This research aims to improve the efficiency of inspection policy and reduce the duration of detention by developing a data-driven Bayesian Network (BN) model using an improved machine-learning (ML) based methodology. New risk variables influencing the duration of ship detention, especially deficiency types, are identified based on the established database containing detention records within the jurisdiction of the Paris MoU from January 2015 to March 2022. Thorough analysis using the developed model allows the identification of deficiency types with a significant impact on the duration of detention, the discovery of interdependencies between these types and the clarification of the major and abnormal deficiency types in different port states. Policy implications and managerial recommendations for port authorities are presented. These include developing clear instructions on types of deficiencies that significantly impact detention time and proposing a selection strategy for vessels in different countries based on their specific circumstances. The proposed model utilizes big data analytics to support the development of inspection policies that are rational and effective. This research will provide good reference for effectively reducing the duration of ship detention, providing policy recommendations, improving ship standards, and ensuring maritime safety.

Nursing of patient with cancer-related insomnia of heart and spleen deficiency type treated with holographic meridian scraping therapy

Nursing of patient with cancer-related insomnia of heart and spleen deficiency type treated with holographic meridian scraping therapy