A rare case of fructose-1,6-bisphosphatase deficiency: a delayed diagnosis story

AbstractObjectivesFructose-1,6-bisphosphatase deficiency (FBPase deficiency, OMIM 229700) is an early-onset rare genetic disorder caused by mutations in the FBP1 gene.Case presentationOur patient was 17-years-old when she was diagnosed with the disease. Initial sequencing analysis with Ion Torrent technology failed to detect the gross deletion that covered complete exon 2 (c.-24-26_170 + 5192del) of FBP1 gene and caused the delay in diagnosis. Deletion was then detected when sequencing was performed in an Illumina MiSeq platform.ConclusionsThis case emphasizes the importance of sequencing data analysis for precise diagnosis of rare diseases and therapy planning.

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Fructose-1,6-bisphosphatase deficiency caused by a novel homozygous Alu element insertion in the FBP1 gene and delayed diagnosis

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0078 ◽

2017 ◽

Vol 30 (6) ◽

pp. 703-706

Author(s):

Somashekara Hosaagrahara Ramakrishna ◽

Siddaramappa Jagdish Patil ◽

Anusha Aladakatte Jagadish ◽

Anil Kumar Sapare ◽

Hiremath Sagar ◽

...

Keyword(s):

Metabolic Disorders ◽

Autosomal Recessive ◽

Delayed Diagnosis ◽

Female Child ◽

Inherited Metabolic Disorders ◽

Fructose 1,6 Bisphosphatase ◽

Alu Element ◽

First Time ◽

Bisphosphatase Deficiency ◽

Fbp1 Gene

AbstractFructose-1,6-bisphosphatase (FBPase) enzyme deficiency is one of the treatable autosomal recessive inherited metabolic disorders. If diagnosed early, FBPase deficiency has a favorable prognosis. We report the clinical and biochemical findings of a 9.5-year-old female child with FBPase deficiency. FBPase deficiency is caused by a homozygousArthrobacter luteus (Alu)insertion in theFBP1gene, reported for the first time.

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Novel FBP1 gene mutations in Arab patients with fructose-1,6-bisphosphatase deficiency

European Journal of Pediatrics ◽

10.1007/s00431-009-0953-9 ◽

2009 ◽

Vol 168 (12) ◽

pp. 1467-1471 ◽

Cited By ~ 18

Author(s):

Muhammad Faiyaz-Ul-Haque ◽

Mohammed Al-Owain ◽

Fouad Al-Dayel ◽

Zuhair Al-Hassnan ◽

Hamad Al-Zaidan ◽

...

Keyword(s):

Gene Mutations ◽

Fructose 1,6 Bisphosphatase ◽

Bisphosphatase Deficiency ◽

Fbp1 Gene

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Exon 2 deletion represents a common mutation in Turkish patients with fructose-1,6-bisphosphatase deficiency

Metabolic Brain Disease ◽

10.1007/s11011-019-00455-8 ◽

2019 ◽

Vol 34 (5) ◽

pp. 1487-1491 ◽

Cited By ~ 1

Author(s):

Mustafa Kılıç ◽

Çiğdem Seher Kasapkara ◽

Didem Yücel Yılmaz ◽

Rıza Köksal Özgül

Keyword(s):

Common Mutation ◽

Exon 2 ◽

Fructose 1,6 Bisphosphatase ◽

Turkish Patients ◽

Bisphosphatase Deficiency

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Younger age of onset and uveitis associated with HLA-B27 and delayed diagnosis in Thai patients with axial spondyloarthritis

Scientific Reports ◽

10.1038/s41598-021-93001-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Naphruet Limsakul ◽

Praveena Chiowchanwisawakit ◽

Parichart Permpikul ◽

Yubolrat Thanaketpaisarn

Keyword(s):

Regression Analysis ◽

Multiple Regression Analysis ◽

Axial Spondyloarthritis ◽

Age At Onset ◽

Delayed Diagnosis ◽

Musculoskeletal Symptom ◽

Hla B27 ◽

Delay In Diagnosis ◽

Factors Associated ◽

Younger Age

AbstractTo identify characteristics associated with HLA-B27, and to identify factors associated with delayed diagnosis in Thai patients with axial spondyloarthritis (axSpA). This cross-sectional study included Thai patients were diagnosed with axSpA by a rheumatologist at Siriraj Hospital. Clinical data were collected. Regression analyses were employed to identify factors associated with study outcomes. Of total 177 patients, 127 (72%) were positive HLA-B27. Uveitis [Odds ratio (OR) 4.0], age at onset of the first musculoskeletal symptom of ≤ 28 years [OR 3.5], female [OR 0.4], and psoriasis [OR 0.4] were significantly associated with HLA-B27 in multiple regression analysis. Those with positive HLA-B27 had less spinal flexibility. Elevated C-reactive protein (p = 0.012) was associated with shorter delay in diagnosis, while uveitis (p < 0.001) and younger age at onset of the first symptom (p = 0.002) were associated with longer delay in diagnosis in multiple regression analysis. Younger age at onset of the first musculoskeletal symptom and uveitis were associated with HLA-B27 and delayed diagnosis in axSpA patients. Young people with musculoskeletal symptom and uveitis should be referred to a rheumatologist to rule out or make a timely diagnosis of axSpA.

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BiSulfite Bolt: A bisulfite sequencing analysis platform

GigaScience ◽

10.1093/gigascience/giab033 ◽

2021 ◽

Vol 10 (5) ◽

Author(s):

Colin Farrell ◽

Michael Thompson ◽

Anela Tosevska ◽

Adewale Oyetunde ◽

Matteo Pellegrini

Keyword(s):

Data Aggregation ◽

Bisulfite Sequencing ◽

Low Complexity ◽

Sequencing Analysis ◽

Command Line ◽

Sequencing Data ◽

Bisulfite Sequencing Data ◽

Analysis Platform ◽

Python Package ◽

Bisulfite Sequencing Analysis

Abstract Background Bisulfite sequencing is commonly used to measure DNA methylation. Processing bisulfite sequencing data is often challenging owing to the computational demands of mapping a low-complexity, asymmetrical library and the lack of a unified processing toolset to produce an analysis-ready methylation matrix from read alignments. To address these shortcomings, we have developed BiSulfite Bolt (BSBolt), a fast and scalable bisulfite sequencing analysis platform. BSBolt performs a pre-alignment sequencing read assessment step to improve efficiency when handling asymmetrical bisulfite sequencing libraries. Findings We evaluated BSBolt against simulated and real bisulfite sequencing libraries. We found that BSBolt provides accurate and fast bisulfite sequencing alignments and methylation calls. We also compared BSBolt to several existing bisulfite alignment tools and found BSBolt outperforms Bismark, BSSeeker2, BISCUIT, and BWA-Meth based on alignment accuracy and methylation calling accuracy. Conclusion BSBolt offers streamlined processing of bisulfite sequencing data through an integrated toolset that offers support for simulation, alignment, methylation calling, and data aggregation. BSBolt is implemented as a Python package and command line utility for flexibility when building informatics pipelines. BSBolt is available at https://github.com/NuttyLogic/BSBolt under an MIT license.

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Educational aspects of rare and orphan lung diseases

Respiratory Research ◽

10.1186/s12931-021-01676-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Tiago M. Alfaro ◽

Marlies S. Wijsenbeek ◽

Pippa Powell ◽

Daiana Stolz ◽

John R. Hurst ◽

...

Keyword(s):

Lung Diseases ◽

Healthcare Professionals ◽

Treatment Options ◽

Delayed Diagnosis ◽

Reference Network ◽

Delay In Diagnosis ◽

Positive Effects ◽

European Reference Network ◽

Patient Representatives ◽

Rare Lung Diseases

AbstractPeople with rare lung diseases often suffer the burden of delayed diagnosis, limited treatment options, and difficulties in finding expert physicians. One of the reasons for the delay in diagnosis is the limited training for healthcare practitioners on rare diseases. This review explores the main concerns and needs for education on rare lung diseases from the perspectives of both patients and professionals. Despite the increasing interest in rare lung disorders and some recent breakthrough developments on the management of several diseases, healthcare professionals, including general practitioners and hospital workers, receive little education on this topic. Nonetheless, many healthcare professionals show much interest in receiving further training, especially on diagnosis. Patients and families want easier access to high-quality education materials to help them manage their own disease. Well-educated patients are better equipped to deal with chronic diseases, but patient education can be challenging as patients’ individual health issues, and diverse backgrounds can create significant barriers. Raising more awareness for rare lung diseases and further development of patient-centred international expert networks like the European Reference Network on Rare Lung Diseases (ERN-LUNG), which includes both experts and patient representatives, are essential for improving care and education on rare lung diseases. Initiatives such as the Rare Disease Day, have been successful in increasing awareness for rare conditions. The development of online tools for accessing information has had positive effects and should be further supported and extended in the future.

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Detection of PKD1 and PKD2 Somatic Variants in Autosomal Dominant Polycystic Kidney Cyst Epithelial Cells by Whole-Genome Sequencing

Journal of the American Society of Nephrology ◽

10.1681/asn.2021050690 ◽

2021 ◽

pp. ASN.2021050690

Author(s):

Zhengmao Zhang ◽

Hanwen Bai ◽

Jon Blumenfeld ◽

Andrew Ramnauth ◽

Irina Barash ◽

...

Keyword(s):

Autosomal Dominant ◽

Genetic Disorder ◽

Fragile Sites ◽

Whole Genome ◽

Sequencing Analysis ◽

Polycystic Kidney ◽

Second Hit ◽

Kidney Cyst ◽

Kidney Cysts ◽

Autosomal Dominant Polycystic Kidney

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the development of multiple cysts in the kidneys. It is often caused by pathogenic mutations in PKD1 and PKD2 genes that encode polycystin proteins. Although the molecular mechanisms for cystogenesis are not established, concurrent inactivating germline and somatic mutations in PKD1 and PKD2 have been previously observed in renal tubular epithelium (RTE). Methods: To further investigate the cellular recessive mechanism of cystogenesis in RTE, we conducted whole-genome DNA sequencing analysis to identify germline variants and somatic alterations in RTE of 90 unique kidney cysts obtained during nephrectomy from 24 unrelated participants. Results: Kidney cysts were overall genomically stable, with low burdens of somatic short mutations or large-scale structural alterations. Pathogenic somatic "second hit" alterations disrupting PKD1 or PKD2 were identified in 93% of the cysts. Of these, 77% of cysts acquired short mutations in PKD1 or PKD2; specifically, 60% resulted in protein truncations (nonsense, frameshift, or splice site) and 16.7% caused non-truncating mutations (missense, in-frame insertions, or deletions). Another ~18% of cysts acquired somatic chromosomal loss of heterozygosity (LOH) events encompassing PKD1 or PKD2 ranging from 2.6 to 81.3 Mb. 14.4% of these cysts harbored copy number neutral LOH events, while the other 3.3% had hemizygous chromosomal deletions. LOH events frequently occurred at chromosomal fragile sites, or in regions comprising chromosome microdeletion diseases/syndromes. Almost all somatic "second hit" alterations occurred at the same germline mutated PKD1/2 gene. Conclusions: These findings further support a cellular recessive mechanism for cystogenesis in ADPKD primarily caused by inactivating germline and somatic variants of PKD1 or PKD2 genes in kidney cyst epithelium.

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Risk factors for the delayed diagnosis of extrapulmonary TB

The International Journal of Tuberculosis and Lung Disease ◽

10.5588/ijtld.20.0788 ◽

2021 ◽

Vol 25 (3) ◽

pp. 191-198

Author(s):

M. K. Lee ◽

C. Moon ◽

M. J. Lee ◽

Y. G. Kwak ◽

E. Lee ◽

...

Keyword(s):

Risk Factors ◽

Outpatient Clinic ◽

Diagnostic Testing ◽

Delayed Diagnosis ◽

Clinical Manifestations ◽

Diagnosis And Treatment ◽

Delay In Diagnosis ◽

Microbiological Characteristics ◽

Significant Difference ◽

Basic Characteristics

BACKGROUND: Extrapulmonary TB (EPTB) is more difficult to diagnose than pulmonary TB. The delayed management of EPTB can lead to complications and increase the socio-economic burden.METHODS: Patients newly diagnosed with EPTB were retrospectively enrolled from 11 general hospitals in South Korea from January 2017 to December 2018. The basic characteristics of patients were described. Univariable and multivariable analyses were performed between early and delayed diagnosis groups to identify risk factors for delayed diagnosis and treatment in EPTB.RESULTS: In total, 594 patients were enrolled. Lymph node TB (28.3%) was the predominant form, followed by abdominal (18.4%) and disseminated TB (14.5%). Concurrent lung involvement was 17.8%. The positivity of diagnostic tests showed no significant difference between the two groups. Acute clinical manifestations in disseminated, pericardial and meningeal TB, and immunosuppression were associated with early diagnosis. Delayed diagnosis was associated with outpatient clinic visits, delayed sample acquisition and diagnostic departments other than infection or pulmonology.CONCLUSION: The delay in diagnosis and treatment of EPTB was not related to differences in microbiological characteristics of Mycobacterium tuberculosis itself; rather, it was due to the indolent clinical manifestations that cause referral to non-TB-specialised departments in the outpatient clinic and delay the suspicion of TB and diagnostic testing.

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A METAGENOMIC ASSESSMENT OF BACTERIAL CONTAMINATION OF DUST EVENTS IN SENEGAL

International Journal of Advanced Research ◽

10.21474/ijar01/12610 ◽

2021 ◽

Vol 9 (03) ◽

pp. 509-526

Author(s):

Alioune Marone ◽

◽

Malick Mbengue ◽

Gregory Jenkins ◽

Demba Ndao Niang ◽

...

Keyword(s):

Respiratory Diseases ◽

Rrna Gene ◽

Source Population ◽

Sequencing Analysis ◽

Human Pathogens ◽

Sequencing Data ◽

Bacterial Populations ◽

African Dust ◽

Hypervariable Regions ◽

Dust Events

Previous work in the Caribbean and West Africa have shown that air samples taken during dust events contain microorganisms (bacteria, fungi, viruses), including human pathogens that can cause many respiratory diseases. To better understand the potential downstream effect of bacteria dust on human health and public ecosystems, it is important to characterize the source population. In this study, we aimed to explore the bacterial populations of African dust samples collected between 2013-2017. The dust samples were collected using the spatula method, then the hypervariable regions (V3 and V4) of the 16S rRNA gene were amplified using PCR followed byMiSeq Illumina sequencing. Analysis of the sequencing data were performed using MG-RAST. At the phylum level, the proportions of Actinobacteria (22%), Firmicutes (20%), Proteobacteria (19%), and Bacteroidetes (13%) were respectively predominant in all dust samples. At the genus level, Bacillus(16%), Pseudomonas(10%), Nocardiodes and Exiguobacterium (5%) are the most dominated genera in African dust samples collected in this study.The study showed that molecular characterization of dust microbial population remains a very efficient method, also applicable to the search for viruses and fungi in this type of sample. It is important to note that the majority of microorganisms identified in this study can cause respiratory diseases.

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Co-Treatment with Single and Ternary Mixture Gas of Dimethyl Sulfide, Propanethiol, and Toluene by a Macrokinetic Analysis in a Biotrickling Filter Seeded with Alcaligenes sp. SY1 and Pseudomonas Putida S1

Fermentation ◽

10.3390/fermentation7040309 ◽

2021 ◽

Vol 7 (4) ◽

pp. 309

Author(s):

Yiming Sun ◽

Xiaowei Lin ◽

Shaodong Zhu ◽

Jianmeng Chen ◽

Yi He ◽

...

Keyword(s):

Ternary Mixture ◽

Dimethyl Sulfide ◽

Illumina Miseq ◽

Industrial Applications ◽

Biotrickling Filter ◽

Sequencing Analysis ◽

Organic Sulfur Compounds ◽

Volatile Organic ◽

Bacterial Groups ◽

Maximum Removal

The biotrickling filter (BTF) treatment is an effective way of dealing with air pollution caused by volatile organic compounds (VOCs). However, this approach is typically used for single VOCs treatment but not for the mixtures of VOC and volatile organic sulfur compounds (VOSCs), even if they are often encountered in industrial applications. Therefore, we investigated the performance of BTF for single and ternary mixture gas of dimethyl sulfide (DMS), propanethiol, and toluene, respectively. Results showed that the co-treatment enhanced the removal efficiency of toluene, but not of dimethyl sulfide or propanethiol. Maximum removal rates (rmax) of DMS, propanethiol and toluene were calculated to be 256.41 g·m−3·h−1, 204.08 g·m−3·h−1 and 90.91 g·m−3·h−1, respectively. For a gas mixture of these three constituents, rmax was measured to be 114.94 g·m−3·h−1, 104.17 g·m−3·h−1 and 99.01 g·m−3·h−1, separately. Illumina MiSeq sequencing analysis further indicated that Proteobacteria and Bacteroidetes were the major bacterial groups in BTF packing materials. A shift of bacterial community structure was observed during the biodegradation process.

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