Phenotypic Variability of Krabbe Disease Across the Lifespan

Krabbe disease (galactocerebrosidase deficiency) is an inherited leukodystrophy that results in severe neurological defects due to altered myelination. Classically, disease onset is within the first year of life. Juvenile and adult-onset cases may have less classic presentations, making diagnosis difficult and often delayed. Here, we review the literature to demonstrate the hetereogeneity of presenting symptoms across all age groups. We also discuss diagnostic approach, emphasizing variation in biochemical, functional, and genetic results among Krabbe phenotypes. Better understanding of the various Krabbe disease phenotypes is critical to facilitate timely diagnosis and appropriate treatment of this clinically heterogeneous disorder.

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Dendritic cells in the mucosa of the human trachea are not regularly found in the first year of life

Thorax ◽

10.1136/thx.56.6.427 ◽

2001 ◽

Vol 56 (6) ◽

pp. 427-431 ◽

Cited By ~ 1

Author(s):

T Tschernig ◽

A S Debertin ◽

F Paulsen ◽

W J Kleemann ◽

R Pabst

Keyword(s):

Dendritic Cells ◽

Sudden Death ◽

Respiratory Tract ◽

Age Groups ◽

First Year ◽

Tracheal Mucosa ◽

Transmission Electron ◽

Human Airways ◽

Tract Infections ◽

First Year Of Life

BACKGROUNDDendritic cells (DCs) in the mucosa of the respiratory tract might be involved in the early development of pulmonary allergy or tolerance. To date, little is known about when the first DCs occur in human airways.METHODSSpecimens of the distal trachea from patients who had died from sudden death in the first year of life (n=29) and in older age groups (n=59) as well as from those who had died from respiratory tract infections in the first year of life (n=8) were examined by immunohistochemistry. Transmission electron microscopy was performed in additional samples from two adults.RESULTSIn the sudden death subgroup DCs were absent in 76% of those who died in the first year of life but were present in 53 of the 59 older cases. All infants who had died of respiratory infectious diseases had DCs in the tracheal mucosa.CONCLUSIONSMature DCs are not constitutively present in the human tracheobronchial mucosa in the first year of life, but their occurrence seems to be triggered by infectious stimuli. These data support the hypothesis that DCs play a crucial role in immunoregulation in early childhood.

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The intensity of natural selection in man

Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character ◽

10.1098/rspb.1912.0073 ◽

1912 ◽

Vol 85 (581) ◽

pp. 469-476 ◽

Cited By ~ 18

Keyword(s):

Natural Selection ◽

Death Rate ◽

Age Groups ◽

First Year ◽

Human Beings ◽

High Infant Mortality ◽

Total Death ◽

Selective Death ◽

First Year Of Life ◽

Varying Environment

(1) In a paper communicated to the Royal Society in 1899, and later in greater elaboration published in ‘Biometrika,’ 1901, it has been shown on the basis of the inheritance of longevity that the selective death-rate in man amounted to at least 60 per cent. to 80 per cent. of the total death-rate. The matter has been recently reconsidered by Prof. Ploetz, who, dealing with material wholly different from that of Beeton and Pearson came to similar conclusions. The point is a very vital one, for, combined with: (i) the heredity of physical and mental characters in man, and (ii) the demonstration that the longer-lived have more offspring, we reach a definite knowledge that Darwinism does apply, and very intensely applies, even to man under civilised conditions. The difficulty of a direct investigation of the problem lies in securing uniformity of environment. W e have to demonstrate that when under the same environment there is a heavier death-rate among a given group of human beings, then among the survivors of this group in a given later period the death-rate will be lessened. Now each group of individuals we attempt to deal with has its own environment, and if that is a bad environment we should expect to find a heavy death-rate both at the earlier and later periods; this obviously must obscure the action of natural selection. For example in districts with a high infant mortality we might expect a high child mortality, say deaths from two to five years of life, because a bad environment sends up the intensity of both. The correlation between deaths in the first year of life (0—1) and in the next four years of life (1—5) for a given district will certainly be positive if no correction be made for varying environment. Quite recently this matter has been discussed by determining the correlation between the ages 0—1 and 1—5 in the administrative counties of England and Wales. As ( a ) the group 0—1 was not followed to 1—5, but the deaths in these age-groups for the same years were dealt with, and ( b ) no allowance whatever was made for the differential environment of the administrative counties, it is difficult to find any real bearing of the data on the problem of natural selection in man.

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P01-303-Vegetative status in infants of high-risk for schizophrenia

European Psychiatry ◽

10.1016/s0924-9338(11)72014-4 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 305-305

Author(s):

M.A. Kalinina ◽

G.N. Schimonova

Keyword(s):

High Risk ◽

Mental State ◽

Motor Development ◽

Prognostic Significance ◽

Age Groups ◽

Control Group ◽

First Year ◽

Autonomic Tone ◽

Autonomic Disorders ◽

First Year Of Life

IntroductionThe study of clinical features and prognostic significance of autonomic disorders are among the most pressing problems of modern medicine.ObjectivesDynamically within 5 years were observed 50 children at high risk for schizophrenia and 40 children with hypoxic-ischemic encephalopathy of the general population. Aims. Evaluation of prognostic significance of autonomic disorders in infancy for mental health in older age groups.MethodsAll patients were examined by clinical methods and EEG, neurosonografia, original screening tables for early childhood.ResultsIn the first year of life in children at high risk for schizophrenia observed mental and motor development within the syndrome of PDD.In infancy the vagotonic orientation prevailed 72, 5%. By 3 years it changed to the amphotonic orientation reaching 76, 0% of children, while the 10, 0% acquired sympathotony, the rest remained vagotonic.The mental state of 37 children to 5 years qualified as schizotipical disorder (F 21.8). In 13 children it was diagnosed schizophrenia, children's type (F20.8). Frequent and sudden changes in the type of tonus correlated with the deterioration of the mental state of a different nature.In the control group at the first year of life prevailed vagotonic orientation, which gradually to age of one year changed by eutonic. During the first 3–5 months of infancy revealed some unstable circulatory, sleep disorders.ConclusionsThe instability of autonomic tone and an abundance of vegetative violations indicate the risk of mental pathology.

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Effectiveness of Rotarix® vaccine in Africa in the first decade of progressive introduction, 2009-2019: systematic review and meta-analysis

Wellcome Open Research ◽

10.12688/wellcomeopenres.16174.2 ◽

2020 ◽

Vol 5 ◽

pp. 187

Author(s):

Nickson Murunga ◽

Grieven P. Otieno ◽

Marta Maia ◽

Charles N. Agoti

Keyword(s):

Meta Analysis ◽

Age Groups ◽

Developed Countries ◽

Point Estimate ◽

First Year ◽

Full Dose ◽

Newcastle Ottawa Scale ◽

Group A ◽

First Year Of Life

Background: Randomized controlled trials of licensed oral rotavirus group A (RVA) vaccines, indicated lower efficacy in developing countries compared to developed countries. We investigated the pooled effectiveness of Rotarix® in Africa in 2019, a decade since progressive introduction began in 2009. Methods: A systematic search was conducted in PubMed to identify studies that investigated the effectiveness of routine RVA vaccination in an African country between 2009 and 2019. A meta-analysis was undertaken to estimate pooled effectiveness of the full-dose versus partial-dose of Rotarix® (RV1) vaccine and in different age groups. Pooled odds ratios were estimated using random effects model and the risk of bias assessed using Newcastle-Ottawa scale. The quality of the evidence was assessed using GRADE. Results: By December 2019, 39 (72%) countries in Africa had introduced RVA vaccination, of which 34 were using RV1. Thirteen eligible studies from eight countries were included in meta-analysis for vaccine effectiveness (VE) of RVA by vaccine dosage (full or partial) and age categories. Pooled RV1 VE against RVA associated hospitalizations was 44% (95% confidence interval (CI) 28-57%) for partial dose versus 58% (95% CI 50-65%) for full dose. VE was 61% (95% CI 50-69%), 55% (95% CI 32-71%), 56% (95% CI 43-67%), and 61% (95% CI 42-73%) for children aged <12 months, 12-23 months, <24 months and 12-59 months, respectively. Conclusion: RV1 vaccine use has resulted in a significant reduction in severe diarrhoea in African children and its VE is close to the efficacy findings observed in clinical trials. RV1 VE point estimate was higher for children who received full dose than those who received partial dose, and its protection lasted beyond the first year of life.

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STUDIES IN SICKLE CELL ANEMIA

PEDIATRICS ◽

10.1542/peds.14.3.209 ◽

1954 ◽

Vol 14 (3) ◽

pp. 209-214

Author(s):

ROLAND B. SCOTT ◽

LELABELLE C. FREEMAN ◽

ANGELLA D. FERGUSON

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Sickle Cell Trait ◽

Age Groups ◽

Test Group ◽

Progressive Increase ◽

First Year ◽

Older Children ◽

Low Incidence ◽

First Year Of Life

This survey of 1100 Negro children in various age categories was undertaken to determine the effect of age upon the appearance of the sickling phenomenon from infancy throughout childhood. The general incidence of sickling in 1100 Negro children including sickle cell anemia and sickle cell trait was 7.4%. The data on the incidence of the asymptomatic sickling trait and of sickle cell anemia are summarized by age and sex in Tables I and II. We encountered 22 cases of sickle anemia, seven of which were previously undiagnosed and unknown. Sixteen cases of sickle cell anemia in males and six in females were encountered in the total test group, comprising 651 males and 449 females. This investigation disclosed 60 subjects bearing the asymptomatic sickling trait. There were 40 and 20 instances of asymptomatic sickling observed in 635 males and 443 females, respectively. When the sexes were divided into two age categories (1 month through 4 years and 5 years through 16 years), there was an actual decrease in the incidence of sickling in the girls and an increase in the sickling phenomenon in the boys. We have no explanation for this finding. The overall incidence of the sickling trait for both sexes in all age groups represents no significant deviation from a 1:1 ratio. The data available from this study failed to disclose a definite progressive increase in the incidence of sickling in the age groups studied. Quantitatively the general transition from the low incidence of sickling in the newborn (3.4%) to the higher occurrence in older children (7.5%) apparently takes place during the first year of life. Additional studies of both a qualitative and quantitative nature and involving a detailed age breakdown during the first year of life would probably elucidate this period of transition.

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Abstract 150: Determining Changes in Contractility, Myofilament Expression and Myofilament Sensitivity in the Developing Human Ventricle

Circulation Research ◽

10.1161/res.111.suppl_1.a150 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Brian H Crawford ◽

Talib Saafir ◽

Gitanjali Baroi ◽

Ming Shen ◽

Ronald Joyner ◽

...

Keyword(s):

Troponin I ◽

Troponin T ◽

Heart Defects ◽

Age Groups ◽

First Year ◽

Ventricular Cells ◽

Developmental Age ◽

Significant Difference ◽

First Year Of Life ◽

Left Heart Syndrome

As pediatric cardiac surgery is increasingly performed in the first year of life, the need for understanding contractility regulation becomes increasingly important. We examined contractility and myofilament changes in ventricular biopsies removed as part of the surgical correction of congenital heart defects from newborns (NB) (hypoplastic left heart syndrome, < 1 wk old) and infants (IF) (tetralogy of Fallot, 3-12 mo old). Sarcomere shortening and calcium (Ca) transients were measured in isolated ventricular cells stimulated at 0.5 and 1 Hz. Increasing pacing frequency caused a significant increase in sarcomere shortening (p< 0.05)in only the IF, but the Ca transient amplitude was relatively unchanged in both groups. Consistent with work in the developing rat heart, we found an isoform switch with increasing developmental age in myofilament proteins, troponin T (TnT) and troponin I (TnI). Western blot analysis revealed that total TnI (the sum of cardiac TnI (cTnI) and slow skeletal TnI (ssTnI)) was not significantly different between the two age groups. However, when comparing only the cTnI isoforms, we found that the NB had a significantly lower levels compared to the IF (11556±789 a.u. vs. 21770±1700 a.u., p<0.001). Analysis of the RT-PCR revealed nearly significant lower levels of TnT isoform 1 in the IF group than the NB group (p=0.078), no significant difference in the levels of TnT isoform 2 (p= 0.536), and significantly higher levels of TnT isoform 3 in the IF group than the NB group (p= 0.039). We also observed developmental changes in myofilament sensitivity to calcium as assessed by measuring the gradient of the fura-2 cell length trajectory on phase-plane diagrams during the late relaxation of the twitch contraction. These results collectively suggest that contractility and myofilament changes, or the lack of changes, may serve as targets for clarifying elements associated with cardiac dysfunction in the developing human ventricle.

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COVID-19 and Adult-onset Still’s Disease as part of Hyperferritinemic Syndromes

Modern Rheumatology Case Reports ◽

10.1093/mrcr/rxab032 ◽

2021 ◽

Author(s):

Tatsuya Kawasaki ◽

Seido Ooka ◽

Machiko Mizushima ◽

Yuta Nakamura ◽

Hiroki Ikeda ◽

...

Keyword(s):

Clinical Symptoms ◽

Disease Onset ◽

Adult Onset Still’S Disease ◽

Adult Onset ◽

Clinical Markers ◽

Still’S Disease ◽

Low Oxygen ◽

Still's Disease ◽

Appropriate Treatment ◽

Adult Onset Still's Disease

Abstract The coronavirus disease (COVID-19) is known to cause hyperferritinemia and hemophagocytic lymphohistiocytosis (HLH). Including this laboratory parameter, clinical symptoms similar to COVID-19 have been observed in adult-onset Still’s disease (AOSD), catastrophic antiphospholipid syndrome (CAPS), macrophage activation syndrome (MAS), and septic shock, which has led to the proposal of a concept called ‘hyperferritinemic syndromes.’ Additionally, high levels of some clinical markers in both COVID-19 and AOSD make them difficult to differentiate. While the efficacy of ciclesonide had been expected for mild pneumonia with COVID-19, the efficacy of tocilizumab, which is a known treatment for AOSD, was not established. Here, we report the first known occurrence of COVID-19, diagnosed in March 2020, preceded by the diagnosis of AOSD, in April 2019, in a 65-year-old, otherwise healthy man. Following the diagnosis of the latter, the patient was first given prednisolone and then tocilizumab, which led to remission. With the recurrence of joint pain and rash in March 2020, accompanied by low oxygen saturation levels (90%), and ground-glass appearance on chest CT, PCR test revealed COVID-19 infection. Ciclesonide was started on day 7 of the disease onset, which led to improved inflammatory markers by day 21. Thus, we infer that while tocilizumab is theoretically useful for COVID-19 due to its inhibition of interleukin 6 (IL-6), additional ciclesonide therapy might be required to prevent worsening of the condition. AOSD and COVID-19 must, therefore, be differentiated by levels of ferritin which differ between the two, and appropriate treatment must be allocated.

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Features of etiology and pathogenesis of acute deep vein thrombosis in children of different age groups. Results of a prospective cohort study in parallel groups

Kazan medical journal ◽

10.17816/kmj2019-410 ◽

2019 ◽

Vol 100 (3) ◽

pp. 410-415

Author(s):

I N Nurmeev ◽

L M Mirolubov ◽

L I Batyrshina ◽

N N Nurmeev ◽

M R Gilmutdinov ◽

...

Keyword(s):

Deep Vein Thrombosis ◽

Age Groups ◽

First Year ◽

Predisposing Factor ◽

Vein Thrombosis ◽

Venous Catheterization ◽

History Of ◽

Acute Deep Vein Thrombosis ◽

First Year Of Life ◽

Deep Vein

Aim. To study the characteristics of the etiology and clinical picture of acute deep vein thrombosis in children of different age groups. Methods. The article analyzes the diagnosis and treatment of 77 children and adolescents with acute deep vein thrombosis. The features of the history of patients, previous fact of deep venous catheterization were studied. The fact of the presence and absence of clinical symptoms of thrombosis is registered. The results of ultrasound diagnostics are used. All patients underwent a course of anticoagulant therapy. The results of diagnosis and treatment were evaluated taking into account the age of the patients, the presence/absence of the history of catheterization of deep veins. Results. When comparing different age groups, their distinctive characteristics were revealed: predominant presence of asymptomatic catheter-associated thrombosis in the younger age group (newborns and infants) with symptomatic deep vein thrombosis of various origin in older children. Among the surveyed, the majority (75.3%) had asymptomatic thrombosis. Pain (2.6%), edema (3.9%) and a combination of pain and edema (18.2%) were more common among symptomatic patients with the symptoms of acute vein thrombosis. In some cases, a combination of two or more complaints was noted. Asymptomatic thrombosis in the catheter-associated thrombosis group amounted to 96.6%. All patients below 1 year had a predisposing factor in the history: 95% - preceding vein catheterization, 5% - postoperative period. With a history of venous catheterization, symptoms of thrombosis were detected 9.2 times less frequently than in children without vein catheterization. In the group of children older than a year, the ratio of thrombosis without a predisposing factor was 10.5%, and the ratio of children with symptoms of thrombosis was 1.38 times higher than among children younger than a year. The only fatal outcome: a 17-year-old patient with a history of thrombophilia, thrombosis of the left iliac vein, pulmonary embolism. Conclusion. Deep vein thrombosis in children of the first year of life in all cases was caused by a predisposing factor: in children during the first year of life in 95% of cases deep vein thrombosis was asymptomatic and was revealed by ultrasound examination.

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PECULIARITIES OF COVID-19 IN CHILDREN OF DIFFERENT AGE GROUPS

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2020-99-6-141-147 ◽

2020 ◽

Vol 99 (6) ◽

pp. 141-147

Author(s):

E.I. Krasnova ◽

◽

G.S. Karpovich ◽

T.V. Komissarova ◽

I.I. Izvekova ◽

...

Keyword(s):

Clinical Picture ◽

Pediatric Patients ◽

Clinical Symptoms ◽

Clinical Course ◽

Age Groups ◽

Epidemiological Data ◽

First Year ◽

High Incidence ◽

First Year Of Life ◽

Specific Symptoms

Materials and methods: a pilot open observational prospective study of 218 pediatric patients with laboratory-verified COVID-19 diagnosis was performed. The main epidemiological data were analyzed, including the age structure, as well as the features of the clinical course of this disease. The development of COVID-19 pneumonia was recorded in 11,5% of cases (25 patients), while more often pneumonia was recorded in children of the first year of life, as well as over 12 years of age (23,5% and 20% of cases, respectively) than in children of other age groups (p<0,05). CT-1 stage was recorded in 13 patients (52% of cases), CT-2 stage in 10 patients (40% of cases), CT-3 stage in 2 patients (8% of cases). The leading clinical symptoms of COVID-19 in children were: hyperemia of the mucous membranes of the pharynx – 100% of cases (218 patients); increased body temperature – 95,9% of cases (209 patients), while the average figures were 37,6 (36,6; 38,2)0 С; cough – 19,7% of cases (43 patients, of which 21 with pneumonia); diarrhea – 17,9% of cases (39 patients); vomiting – 6,4% of cases (14 patients); change in the auscultatory picture – 3,7% of cases (8 patients with pneumonia). In infants with COVID-19, diarrhea was more often recorded in comparison with patients in the age group over 13 years old (35% and 4% of cases, respectively; p=0,001). The development of cough was less often recorded in children of the first year of life, in Compared with patients over 13 years of age (9% and 40% of cases, respectively; p=0,004), the same trend was observed in COVID-19 pneumonia (25% and 89% of cases, respectively, p=0,02). Thus, the clinical picture of COVID-19 in pediatric patients is characterized by non-specific symptoms. There is a definite trend towards more frequent development of COVID-19 pneumonia in patients in the first year of life, as well as in puberty. Infants with COVID-19 pneumonia are characterized by a high incidence of atypical course of the disease, while adolescents are more likely to show a manifest clinical picture of COVID-19.

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The Perception of Causality in Infants

Perception ◽

10.1068/p110173 ◽

1982 ◽

Vol 11 (2) ◽

pp. 173-186 ◽

Cited By ~ 138

Author(s):

Alan M Leslie

Keyword(s):

Age Groups ◽

First Year ◽

Billiard Ball ◽

Perception Of Causality ◽

First Year Of Life

The problem of the origins of the perception of causality in infancy has received relatively little attention in the literature despite its obvious importance. Two experiments with infants 4 1/2 and 8 months old are reported which seek to investigate sensitivity to spatiotemporal continuity in simple causal events with a differential dishabituation-of-looking technique. In the first experiment inanimate events of the familiar ‘billiard-ball launching’ type were used, while in the second animate events involving a hand/object pick-up were presented. The results suggest that both age groups of infants were sensitive to certain changes in spatiotemporal continuity in both types of event, although in the case of the inanimate stimuli the younger infants reacted less positively. It is suggested that infants in the first year of life are sensitive to certain spatiotemporal event configurations and that this sensitivity could be regarded as at least a required component of a perception of causality.

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