Why does age of onset predict clinical severity in schizophrenia? A multiplex extended pedigree study

Abstract Background The literature is limited on staphylococcal infection in children with cystic fibrosis (CF) from tropical countries. We aimed to study the risk factors and clinical course of children with CF infected with Staphylococcus aureus. Methods In this chart review we compared demographic, clinical and spirometry characteristics in CF children with S. aureus alone (group A), both S. aureus and Pseudomonas aeruginosa (group B) and P. aeruginosa alone (group C) colonization. Results We included 79 cases (group A, 22; group B, 19; group C, 38). There was no difference in age of onset of symptoms, age of diagnosis, age of first isolation and spirometry parameters before colonization between the groups. The median duration of follow-up was shorter in group A. After colonization, children in group A and group B had significantly lower mean Shwachman and Kulczycki (SK) scores (44.7±5.4 and 40.8±5.8, respectively) compared with group C (49.9±6.8). Pulmonary exacerbations and hospitalizations were significantly greater in the combined group. After colonization, group A had a significant deterioration in SK score and forced vital capacity (FVC). Conclusions S. aureus colonization, especially in combination with P. aeruginosa, in children with CF was associated with worsening of FVC and clinical severity score and increased pulmonary exacerbations.

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Voxel-based morphometry in patients with mood disorder bipolar I mania in comparison to normal controls

Egyptian Journal of Radiology and Nuclear Medicine ◽

10.1186/s43055-019-0119-3 ◽

2020 ◽

Vol 51 (1) ◽

Author(s):

Hosam Abozaid Yousef ◽

Yasser Mohamed Bader-Eldein ElSerogy ◽

Sherif Mohamed Abdelal ◽

Shaza Ragab Abdel-Rahman

Keyword(s):

Mood Disorder ◽

Structural Changes ◽

Rating Scale ◽

Age Of Onset ◽

Clinical Severity ◽

Clinical Aspects ◽

Volumetric Data ◽

Voxel Based Morphometry ◽

Young Mania ◽

Neuropsychiatric Diseases

Abstract Background Neuroimaging is used to study brain structural alterations in neuropsychiatric diseases including bipolar disorder (BD). Voxel-based morphometry (VBM) quantifies structural changes detected in magnetic resonance imaging (MRI). The aim of this study was to identify brain structural changes in patients with mood disorder bipolar I mania, compared to healthy controls; and detect any correlations between volumetric findings and different clinical aspects of the disease. VBM was used to identify structural changes in 24 patients with bipolar I mania compared to 16 controls. Young Mania Rating Scale (YMRS) was used to evaluate clinical severity of BD. t test was used to compare differences in volumetric data and Spearman’s rank correlation coefficient was used to detect potential correlations between volumetric data and clinical parameters of BD. Results Compared to controls, BD patients had significantly larger right globus pallidus and right lateral ventricle. There was significant correlation between volumetric data of different brain structures and clinical criteria of BD including age of onset, illness duration, YMRS, number of manic attacks, and duration of the last attack. Conclusions VBM could address specific structural findings in bipolar I mania that may contribute to pathophysiology of the disease and show significant correlation with different clinical aspects of the disease. Trial registration This clinical trial was registered at ClinicalTrials.gov under registration number NCT03181698, registered 11 June 2017.

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A Study of Phenotypic Heterogeneity in Hb E-Beta Thalassemia and Its Correlation with Hb E Level

Blood ◽

10.1182/blood.v124.21.1365.1365 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1365-1365 ◽

Cited By ~ 1

Author(s):

Maitryee Bhattyacharyya ◽

Basab Bagchi ◽

Meet Kumar

Keyword(s):

Disease Severity ◽

Conflicts Of Interest ◽

Age Of Onset ◽

Clinical Phenotype ◽

Phenotypic Heterogeneity ◽

Clinical Severity ◽

Beta Thalassemia ◽

Disease Modifying Drugs ◽

Hb E ◽

Size Growth

Abstract INTRODUCTION: Hb E-beta thalssemia has variable clinical phenotype, varying from NTDT to severe transfusion dependent thalassemia. Factors influencing the severity include HbF level, type of beta mutation, co-inheritance of alpha mutation (including triplication and quadruplication), and various polymorphisms. We evaluate the possible correlation between HbE levels and clinical severity in patients in Hb E-beta thalassemia. AIMS AND OBJECTIVES: To study the phenotypic heterogeneity of Hb E-beta thalassemia patients with respect to Hb E levels. MATERIALS AND METHODS: Patients >18years were enrolled and evaluated for clinical phenotype as per Mahidol score (age of onset, age of first transfusion, requirement for transfusion, spleen size, growth retardation and steady-state hemoglobin), and classified into mild, moderate and severe. Further biochemical data was evaluated including serum ferritin. The clinical phenotype severity was correlated with HbE and HbF levels. Patients on disease modifying drugs (eg hydroxyurea) were excluded. RESULTS: A total of 120 patients of Hb E-beta thalassemia were enrolled with M:E = 1.1:1. 65.8% patients were 18-30 years age range, while 5.8% were above 50years of age. As per Mohidol score, 39.2% (47) patients were mild, 45.8% (55) were moderate and 15% (18) were severe phenotype. Observations amongst patients of different clinical severity are as shown in Table 1. Abstract 1365. Table 1.CharacterMildModerateSevereRangeP valueNumber475518Baseline Hb (g/dl)7.9+-0.96.4+-1.16.2+-0.73.8-10.30.000Age at presentation (years)18.3+-8.7613.1+-8.03.16+-2.081-440.000Age at 1st transfusion (years)22.1+-11.415.1+-8.763.9+-1.91-600.000Freq of transfusion (annual)2.5+-4.512.2+-7.619.3+-11.40-480.000Spleen size (cms)5.6+-2.47.8+-2.910.4+-3.40-150.000Serum ferritin (ng/ml)792.5+-534.61206.5+-523.91570.5+-581.264.2-2924.20.000 Hb E levels of the patients ranged from 28% to 83.5%, and HbF levels ranged from 3.1% to 49.4%. On statistical analysis, difference in HbE levels was significant between severe vs mild and intermediate groups (p=0.0005 and 0.012 respectively), but not amongst mild vs intermediate groups (p=0.21). Also, difference in HbF levels was significant between mild vs moderate and severe groups (p=0.007 and 0.004 respectively), but not between moderate vs severe groups (p=0.26). Regression analysis showed HbF and HbE to be independent parameters of severity and both have negative correlation with disease severity. CONCLUSION: HbE is an independent parameter of severity and correlated negatively with disease severity in HbE-beta thalassemia. Disclosures No relevant conflicts of interest to declare.

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Assessing disease severity by hsCRP as a biochemical marker for psoriasis

International Journal of Research in Dermatology ◽

10.18203/issn.2455-4529.intjresdermatol20175373 ◽

2017 ◽

Vol 3 (4) ◽

pp. 501

Author(s):

Kriti Jain ◽

Arvind Krishna ◽

B. S. Rathore

Keyword(s):

Disease Severity ◽

Age Of Onset ◽

Late Onset ◽

Severe Disease ◽

High Sensitivity ◽

The Body ◽

Clinical Severity ◽

Positive Correlation ◽

Reactive Protein ◽

Pasi Score

Background: For a complex chronic disease like psoriasis, having a biomarker to objectively assess the clinical severity can be very helpful in disease management.Methods: In a hospital based prospective study, 70 patients of psoriasis diagnosed clinically, were studied. The extent of disease severity was assessed using PASI and BSA and patients were grouped into having mild, moderate and severe disease using these scores. Serum high sensitivity C-reactive protein (hsCRP) levels were then estimated for each group.Results: Of the 70 psoriasis cases enrolled, 46 patients were male and 24 females. Patients with early onset psoriasis were associated with higher values of hsCRP than those with late onset (r=-0.063; p=0.012). A positive correlation was seen between the PASI score and hsCRP levels (r=0.891; p≤0.001). On comparing mean PASI and mean hsCRP in severity groups (mild, moderate and severe), hsCRP was higher in the group with maximum severity (p≤0.001). Conclusions: A negative correlation between the age of onset and hsCRP implies that, earlier the age of onset, higher is the value of hsCRP. Our study shows a positive correlation between the body surface area and PASI score both of which varied linearly with hsCRP values. The findings also suggest that patients with severe psoriasis have higher mean serum hsCRP levels than patients with mild psoriasiss.We proposed hsCRP as a useful marker of psoriasis severity that could be used to monitor psoriasis and, together with PASI, as a global index of disease severity.

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Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations

Blood ◽

10.1182/blood-2010-08-299917 ◽

2011 ◽

Vol 117 (14) ◽

pp. 3759-3769 ◽

Cited By ~ 62

Author(s):

Maria Castella ◽

Roser Pujol ◽

Elsa Callén ◽

Juan P. Trujillo ◽

José A. Casado ◽

...

Keyword(s):

Fanconi Anemia ◽

Functional Role ◽

Age Of Onset ◽

Hot Spot ◽

Bone Marrow Failure ◽

Clinical Impact ◽

Clinical Severity ◽

Molecular Evidence ◽

Missense Mutations ◽

Long Distance

Abstract Fanconi anemia is characterized by congenital abnormalities, bone marrow failure, and cancer predisposition. To investigate the origin, functional role, and clinical impact of FANCA mutations, we determined a FANCA mutational spectrum with 130 pathogenic alleles. Some of these mutations were further characterized for their distribution in populations, mode of emergence, or functional consequences at cellular and clinical level. The world most frequent FANCA mutation is not the result of a mutational “hot-spot” but results from worldwide dissemination of an ancestral Indo-European mutation. We provide molecular evidence that total absence of FANCA in humans does not reduce embryonic viability, as the observed frequency of mutation carriers in the Gypsy population equals the expected by Hardy-Weinberg equilibrium. We also prove that long distance Alu-Alu recombination can cause Fanconi anemia by originating large interstitial deletions involving FANCA and 2 adjacent genes. Finally, we show that all missense mutations studied lead to an altered FANCA protein that is unable to relocate to the nucleus and activate the FA/BRCA pathway. This may explain the observed lack of correlation between type of FANCA mutation and cellular phenotype or clinical severity in terms of age of onset of hematologic disease or number of malformations.

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Age of onset and clinical severity in Alzheimer's disease: Neuropathologic and neurochemical correlates

Biological Psychiatry ◽

10.1016/0006-3223(90)90083-e ◽

1990 ◽

Vol 27 (9) ◽

pp. 43

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Age Of Onset ◽

Clinical Severity ◽

Neurochemical Correlates

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Genetic approaches to the treatment of inherited neuromuscular diseases

Human Molecular Genetics ◽

10.1093/hmg/ddz131 ◽

2019 ◽

Vol 28 (R1) ◽

pp. R55-R64 ◽

Cited By ~ 6

Author(s):

Bhavya Ravi ◽

Anthony Antonellis ◽

Charlotte J Sumner ◽

Andrew P Lieberman

Keyword(s):

Motor Neurons ◽

Viral Vectors ◽

Age Of Onset ◽

Muscular Atrophy ◽

Neuromuscular Disorders ◽

Neuromuscular Diseases ◽

Clinical Severity ◽

Charcot Marie Tooth Disease ◽

Degenerative Disorders ◽

Clinical Benefits

Abstract Inherited neuromuscular diseases are a heterogeneous group of developmental and degenerative disorders that affect motor unit function. Major challenges toward developing therapies for these diseases include heterogeneity with respect to clinical severity, age of onset and the primary cell type that is affected (e.g. motor neurons, skeletal muscle and Schwann cells). Here, we review recent progress toward the establishment of genetic therapies to treat inherited neuromuscular disorders that affect both children and adults with a focus on spinal muscular atrophy, Charcot–Marie–Tooth disease and spinal and bulbar muscular atrophy. We discuss clinical features, causative mutations and emerging approaches that are undergoing testing in preclinical models and in patients or that have received recent approval for clinical use. Many of these efforts employ antisense oligonucleotides to alter pre-mRNA splicing or diminish target gene expression and use viral vectors to replace expression of mutant genes. Finally, we discuss remaining challenges for optimizing the delivery and effectiveness of these approaches. In sum, therapeutic strategies for neuromuscular diseases have shown encouraging results, raising hope that recent strides will translate into significant clinical benefits for patients with these disorders.

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The age of onset of substance use is related to the coping strategies to deal with treatment in men with substance use disorder

PeerJ ◽

10.7717/peerj.3660 ◽

2017 ◽

Vol 5 ◽

pp. e3660 ◽

Cited By ~ 6

Author(s):

Maria del Mar Capella ◽

Ana Adan

Keyword(s):

Social Support ◽

Substance Use ◽

Coping Strategies ◽

Age Of Onset ◽

Social Withdrawal ◽

Continuous Variable ◽

Assessment Tools ◽

Clinical Severity ◽

Clinical State ◽

Clinical Prognosis

BackgroundThe age of onset of substance use (OSU) as well as the coping strategies (CS) influence both the development and the course of Substance Use Disorders (SUD). We aim to examine the differences in the CS applied to deal with treatment in men with SUD, considering whether the age of OSU had begun at age 16 or earlier (OSU ≤ 16) or at 17 years or later (OSU ≥ 17), as well as the associations of the CS with clinical variables were studied.MethodsA total of 122 patients with at least three months of abstinence, 60 with OSU≤16 and 62 with OSU≥17, were evaluated through the Coping Strategies Inventory and clinical assessment tools.ResultsThe OSU≤16 patients were younger and presented a worse clinical state. Compared to the norms, the SUD patients were less likely to use adaptive CS, although this was more remarkable for the OSU≤16 group. Furthermore, the OSU≤16 patients presented a CS pattern of higher Disengagement, with lesser use of Social Support and higher Problem Avoidance and Social Withdrawal. In the whole SUD sample, the severity of addiction, number of relapses and age of OSU (as a continuous variable) were related to maladaptive coping. Nevertheless, the cut-off age of OSU modulated these results.ConclusionsThe OSU≤16 was a risk factor for presenting greater clinical severity and a more dysfunctional CS profile to deal with treatment. Thus, the cut-off age considered has allowed us to differentiate SUD patients with more vulnerability to present worse clinical prognosis who may require specific prevention and rehabilitation strategies discussed throughout this work.

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Variable age of onset and clinical severity in transferrin receptor 2 related haemochromatosis: novel observations

British Journal of Haematology ◽

10.1111/bjh.12350 ◽

2013 ◽

Vol 162 (2) ◽

pp. 278-281 ◽

Cited By ~ 13

Author(s):

Edouard Bardou-Jacquet ◽

Severine Cunat ◽

Marie-Pascale Beaumont-Epinette ◽

Caroline Kannengiesser ◽

Xavier Causse ◽

...

Keyword(s):

Transferrin Receptor ◽

Age Of Onset ◽

Clinical Severity ◽

Transferrin Receptor 2

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Mutational Analysis and mtDNA Haplogroup Characterization in Three Serbian Cases of Mitochondrial Encephalomyopathies and Literature Review

Diagnostics ◽

10.3390/diagnostics11111969 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1969

Author(s):

Phepy G. A. Dawod ◽

Jasna Jancic ◽

Ana Marjanovic ◽

Marija Brankovic ◽

Milena Jankovic ◽

...

Keyword(s):

Mutational Analysis ◽

Age Of Onset ◽

Single Case ◽

Phenotypic Variability ◽

Leigh Syndrome ◽

Clinical Severity ◽

Sequencing Analysis ◽

Clinical Genetic ◽

Mitochondrial Encephalomyopathies ◽

Mtdna Mutations

Mitochondrial encephalomyopathies (MEMP) are heterogeneous multisystem disorders frequently associated with mitochondrial DNA (mtDNA) mutations. Clinical presentation varies considerably in age of onset, course, and severity up to death in early childhood. In this study, we performed molecular genetic analysis for mtDNA pathogenic mutation detection in Serbian children, preliminary diagnosed clinically, biochemically and by brain imaging for mitochondrial encephalomyopathies disorders. Sanger sequencing analysis in three Serbian probands revealed two known pathogenic mutations. Two probands had a heteroplasmic point mutation m.3243A>G in the MT-TL1 gene, which confirmed mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode syndrome (MELAS), while a single case clinically manifested for Leigh syndrome had an almost homoplasmic (close to 100%) m.8993T>G mutation in the MT-ATP6 gene. After full mtDNA MITOMASTER analysis and PhyloTree build 17, we report MELAS’ association with haplogroups U and H (U2e and H15 subclades); likewise, the mtDNA-associated Leigh syndrome proband shows a preference for haplogroup H (H34 subclade). Based on clinical–genetic correlation, we suggest that haplogroup H may contribute to the mitochondrial encephalomyopathies’ phenotypic variability of the patients in our study. We conclude that genetic studies for the distinctive mitochondrial encephalomyopathies should be well-considered for realizing clinical severity and possible outcomes.

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