scholarly journals The attenuated end of the phenotypic spectrum in MPS III: from late-onset stable cognitive impairment to a non-neuronopathic phenotype

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Stephanie C. M. Nijmeijer ◽  
L. Ingeborg van den Born ◽  
Anneke J. A. Kievit ◽  
Karolina M. Stepien ◽  
Janneke Langendonk ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Hypertrophic Cardiomyopathy ◽  
Independent Living ◽  
Late Onset ◽  
Retinal Dystrophy ◽  
Case Series ◽  
Lysosomal Storage ◽  
Phenotypic Spectrum ◽  
Whole Exome ◽  
Mps Iii

Abstract Background The phenotypic spectrum of many rare disorders is much wider than previously considered. Mucopolysaccharidosis type III (Sanfilippo syndrome, MPS III), is a lysosomal storage disorder traditionally considered to be characterized by childhood onset, progressive neurocognitive deterioration with a rapidly or slowly progressing phenotype. The presented MPS III case series demonstrates adult onset phenotypes with mild cognitive impairment or non-neuronopathic phenotypes. Methods In this case series all adult MPS III patients with a mild- or non-neuronopathic phenotype, who attend the outpatient clinic of 3 expert centers for lysosomal storage disorders were included. A mild- or non-neuronopathic phenotype was defined as having completed regular secondary education and attaining a level of independency during adulthood, involving either independent living or a paid job. Results Twelve patients from six families, with a median age at diagnosis of 43 years (range 3–68) were included (11 MPS IIIA, 1 MPS IIIB). In the four index patients symptoms which led to diagnostic studies (whole exome sequencing and metabolomics) resulting in the diagnosis of MPS III; two patients presented with retinal dystrophy, one with hypertrophic cardiomyopathy and one with neurocognitive decline. The other eight patients were diagnosed by family screening. At a median age of 47 years (range 19–74) 9 out of the 12 patients had normal cognitive functions. Nine patients had retinal dystrophy and 8 patients hypertrophic cardiomyopathy. Conclusion We show the very mild end of the phenotypic spectrum of MPS III, ranging from late-onset stable neurocognitive impairment to a fully non-neuronopathic phenotype. Awareness of this phenotype could lead to timely diagnosis and genetic counseling.

scholarly journals Mild cognitive impairment in novel SPG11 mutation-related sporadic hereditary spastic paraplegia with thin corpus callosum: case series

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chuan Li ◽  
Qi Yan ◽  
Feng-ju Duan ◽  
Chao Zhao ◽  
Zhuo Zhang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Corpus Callosum ◽  
Hereditary Spastic Paraplegia ◽  
Late Onset ◽  
Case Series ◽  
Spastic Paraplegia ◽  
Thin Corpus Callosum ◽  
Modeling Analysis ◽  
Multiple Domains

Abstract Background SPG11 mutation-related autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is the most common cause in complicated forms of HSP, usually presenting comprehensive mental retardation on early-onset stage preceding spastic paraplegias in childhood. However, there are many instances of sporadic late-onset HSP-TCC cases with a negative family history, and potential mild cognitive deficits in multiple domains may be easily neglected and inaccurately described. Methods In this study, we performed next generation sequencing in four sporadic late-onset patients with HSP-TCC, and combined Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate cognition of the patients. Results By evolutionary conservation and structural modeling analysis, we have revealed 4 novel pathogenic SPG11 mutations, and firstly confirmed mild cognitive impairment (MCI) with normal MMSE scores (≥27) and decreased MoCA scores (< 26) in these SPG11 mutation-related HSP-TCC patients, predominantly presenting impairment of executive function, delayed recall, abstraction and language. Conclusions The results expand the mutational spectrum of SPG11-associated HSP-TCC from sporadic cases, and confirm MCI with combination of decreased MoCA and normal MMSE assessment, suggesting that clinicians should consider doing a MoCA to detect MCI in patients with HSP, particularly those with HSP-TCC.

scholarly journals Dysfunctional Learning and Verbal Memory in Patients with Elevated Tau Protein Levels and Serum Recoverin Autoantibodies—Case Series and Review

2021 ◽  
Vol 12 (1) ◽  
pp. 15
Author(s):  
Niels Hansen ◽  
Claudia Bartels ◽  
Kristin Rentzsch ◽  
Winfried Stöcker ◽  
Dirk Fitzner
Keyword(s):  
Cognitive Impairment ◽  
Pineal Gland ◽  
Tau Protein ◽  
Verbal Memory ◽  
Late Onset ◽  
Case Series ◽  
Depressive Mood ◽  
Formal Thought Disorder ◽  
Autoimmune Retinopathy ◽  
Protein Levels

Recoverin-antibody-related disease is currently restricted to late-onset ataxia and autoimmune retinopathy, which can be paraneoplastic or not. However, cognitive dysfunction associated with recoverin antibodies has not been reported so far in a homogeneous patient group. Our case series is dedicated to describing the novel phenotype of cognitive impairment associated with recoverin antibodies. We included five patients with cognitive impairment who presented serum recoverin autoantibodies detected by immunoblots in our case series investigation. We also analyzed their psychopathology, clinical data, cerebrospinal fluid (CSF), and neuroimaging data. Five patients with cognitive impairment associated with serum recoverin antibodies exhibited profound dysfunctional learning and verbal memory. In the CSF of 40% of them, we also diagnosed axonal neurodegeneration entailing elevated tau and phosphorylated tau protein levels. Psychopathologies such as affective symptoms (restlessness, depressive mood, anxiety, complaintiveness) and formal thought disorder, such as rumination, were detected in 25–75% of the patients. We hypothesized a role of recoverin autoimmunity in the pineal gland involving consecutive modulation of hippocampus-based memory caused by an altered release of melatonin. We describe a novel phenotype of possible recoverin autoimmunity in patients with cognitive impairment. However, no clear diagnostic clues can be extracted because of the low diagnostic validity of the testing strategies applied. The possibility of recoverin antibody autoimmunity in the pineal gland correlating with a modulation of hippocampus-based memory should be further investigated.

Phenotypic cognitive impairment in late-onset delusional disorder

2014 ◽  
Vol 26 (6) ◽  
pp. 965-975 ◽  
Author(s):  
Ben S. Harris ◽  
Eleftheria J. Kotsopoulos ◽  
Sami Yamin
Keyword(s):  
Cognitive Impairment ◽  
Object Recognition ◽  
Processing Speed ◽  
Late Onset ◽  
Case Series ◽  
Delusional Disorder ◽  
High Rate ◽  
Visual Object ◽  
Perceptual Skills ◽  
Conceptual Reasoning

ABSTRACTBackground:Previous use of heterogeneous diagnostic criteria and insensitive cognitive measures has impeded clarification of the extent and type of cognitive impairment specific to late-onset delusional disorder. We examined whether clinical presentations of late-onset delusional disorder are associated with prodromal or established dementia, and whether it might be a discrete clinical syndrome characterized by its own profile of cognitive impairment.Method:Nineteen patients with late-onset delusional disorder from a hospital psychiatric service and 20 patients with dementia of the Alzheimer's type (AD) from an outpatient memory clinic were recruited in a consecutive case series. All patients underwent comprehensive neuropsychological assessment that included general intellectual function, executive function, new learning and delayed memory, language, processing speed, and visuo-perceptual skills.Results:Late-onset delusional disorder patients showed moderate impairment to conceptual reasoning, visual object recognition, processing speed, and confrontation naming. Severe impairment appeared in visuo-perceptual planning and organization, and divided attention. Compared with the Alzheimer's disease (AD) group, the late-onset delusional disorder group demonstrated significantly poorer visuo-perceptual skills but a significantly better capacity to consolidate information into delayed memory.Conclusions:A high rate of marked cognitive impairment occurs in late-onset delusional disorder. There was evidence of a conceptual reasoning deficit, plus the presence of a visuo-perceptual impairment affecting object recognition. This impairment profile can explain the genesis and maintenance of the observed delusions. Understanding late-onset delusional disorder as other than a purely psychiatric phenomenon or a precursor to AD will lead to better assessment and management approaches.

Estimation of premorbid intelligence and executive cognitive functions with lexical reading tasks

2020 ◽  
Author(s):  
Graham Pluck
Keyword(s):  
Cognitive Impairment ◽  
Lexical Decision ◽  
Cognitive Ability ◽  
Memory Span ◽  
Clinical Sample ◽  
Case Series ◽  
Stem Completion ◽  
Clinical Neuropsychology ◽  
Premorbid Intelligence ◽  
Highly Correlated

Introduction: Estimation of premorbid function is essential to accurate assessment of cognitive impairments in clinical neuropsychology and behavioral neurology, and has numerous research applications. However, current methods are rudimentary and imperfect. We explored how lexical tasks can be best used to accurately and precisely estimate intelligence and executive functions.Methods: We studied lexical word pronunciation, lexical decision, and stem-completion naming in the estimation of cognitive ability, in samples of healthy adults (n = 143), and patients with cognitive impairment due to neurological illness (n =15). Cognitive assessments included intelligence (WAIS-IV), episodic memory, and eight tests of executive functioning, including Theory of Mind.Results: When examined at the group level, single word pronunciation was particularly robust in the presence of cognitive impairment in patients with dementia. However, as a case series, patients showed idiosyncratic patterns of preservation of lexical skills including on tests of pronunciation, lexical decision and stem-completion naming. All of these tasks were highly correlated with IQ scores in a non-clinical sample, suggesting that they could be used as estimators of premorbid intelligence. Simulated impairments in non-clinical controls suggested that the median score from the three different tasks had the highest correlation with, and provided the most accurate and precise estimates of, intelligence, and was also the least sensitive to impairment. Finally, we show that these methods also predict executive functions, in particular, strong correlations were found for proverb interpretation, phonemic/semantic alternating verbal fluency, and working memory span performance. Conclusions: Several lexical tasks are potentially useful in predication of pre-illness cognitive ability in patients with neurological or psychiatric illness. However, due to the heterogeneity of impairments between patients, estimation of premorbid levels could be improved by the use of the median estimated values from multiple tests. This could potentially improve diagnostic accuracy and quantification of neuropsychological impairments.

Depression in Dementia or Dementia in Depression? Systematic Review of Studies and Hypotheses

2020 ◽  
Vol 17 (1) ◽  
pp. 16-28 ◽  
Author(s):  
Agnieszka Brzezińska ◽  
Julius Bourke ◽  
Rayito Rivera-Hernández ◽  
Magda Tsolaki ◽  
Joanna Woźniak ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Randomised Controlled Trials ◽  
Late Onset ◽  
Alternative Hypothesis ◽  
Controlled Trials ◽  
Major Depressive ◽  
Future Studies ◽  
Individual Vulnerability ◽  
Current Review ◽  
Randomised Controlled

The majority of research works to date suggest that Major Depressive Disorder (MDD) is a risk factor for dementia and may predispose to cognitive decline in both early and late onset variants. The presence of depression may not, however, reflect the cause, rather, an effect: it may be a response to cognitive impairment or alters the threshold at which cognitive impairment might manifest or be detected. An alternative hypothesis is that depression may be part of a prodrome to Alzheimer’s Disease (AD), suggesting a neurobiological association rather than one of psychological response alone. Genetic polymorphisms may explain some of the variances in shared phenomenology between the diagnoses, the instance, when the conditions arise comorbidly, the order in which they are detected that may depend on individual cognitive and physical reserves, as well as the medical history and individual vulnerability. This hypothesis is biologically sound but has not been systematically investigated to date. The current review highlights how genetic variations are involved in the development of both AD and MDD, and the risk conferred by these variations on the expression of these two disorders comorbidly is an important consideration for future studies of pathoaetiological mechanisms and in the stratification of study samples for randomised controlled trials.

Case Series With Late-Onset Psychosis Hospitalized in a Geriatric Psychiatry Unit in Turkey: Experience in 9 Years

2003 ◽  
Vol 15 (1) ◽  
pp. 69-72 ◽  
Author(s):  
Yesne Alici-Evcimen ◽  
Turan Ertan ◽  
Engin Eker
Keyword(s):  
Early Onset ◽  
Late Onset ◽  
Case Series ◽  
Geriatric Psychiatry ◽  
Delusional Disorder ◽  
Early Onset Schizophrenia ◽  
Treatment Results ◽  
Thought Insertion ◽  
Psychiatry Department ◽  
Paranoid Psychosis

In this article we report the first series of Turkish inpatients with late-onset psychosis, and describe our 9-year experience at the only inpatient geriatric psychiatry department in Turkey. Among 420 patients hospitalized between 1993 and 2002, 27 were psychotic. In this group, eight patients were diagnosed as having late-onset schizophrenia (LOS) and six very-late-onset schizophrenia-like psychosis (VLOSLP). Five patients had early-onset schizophrenia and eight had delusional disorder. Females were more frequently seen in the group with LOS and the group with VLOSLP. Except for one patient with LOS, all patients with VLOSLP and LOS had paranoid psychosis. Nihilistic delusions, delusions of poverty or guilt, thought withdrawal, thought insertion, and thought broadcasting were not seen in any of the patients. Additionally, none of the LOS or VLOSLP patients showed erotomanic delusions. Grandiose and mystic delusions were not seen in those with VLOSLP. Treatment results and antipsychotic dosages at discharge were similar to those in previous reports from other cultures.

LATE-ONSET HYPERTROPHIC CARDIOMYOPATHY

2019 ◽  
Vol 73 (9) ◽  
pp. 2373
Author(s):  
Asad J. Torabi ◽  
Hossein Ouranos ◽  
Richard Kovacs
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Late Onset

scholarly journals Identification of a novel homozygous loss-of-function mutation in FUCA1 gene causing severe fucosidosis: A case report

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110059
Author(s):  
Xinwen Zhang ◽  
Shaozhi Zhao ◽  
Hongwei Liu ◽  
Xiaoyan Wang ◽  
Xiaolei Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Lysosomal Storage Disorder ◽  
Autosomal Recessive ◽  
Signs And Symptoms ◽  
Lysosomal Storage ◽  
Loss Of Function ◽  
Wild Type ◽  
Single Nucleotide ◽  
Whole Exome ◽  
Exon 1

Fucosidosis is a rare lysosomal storage disorder characterized by deficiency of α-L-fucosidase with an autosomal recessive mode of inheritance. Here, we describe a 4-year-old Chinese boy with signs and symptoms of fucosidosis but his parents were phenotypically normal. Whole exome sequencing (WES) identified a novel homozygous single nucleotide deletion (c.82delG) in the exon 1 of the FUCA1 gene. This mutation will lead to a frameshift which will result in the formation of a truncated FUCA1 protein (p.Val28Cysfs*105) of 132 amino acids approximately one-third the size of the wild type FUCA1 protein (466 amino acids). Both parents were carrying the mutation in a heterozygous state. This study expands the mutational spectrum of the FUCA1 gene associated with fucosidosis and emphasises the benefits of WES for accurate and timely clinical diagnosis of this rare disease.

scholarly journals Rare Variants in Autophagy and Non-Autophagy Genes in Late-Onset Pompe Disease: Suggestions of Their Disease-Modifying Role in Two Italian Families

2021 ◽  
Vol 22 (7) ◽  
pp. 3625
Author(s):  
Filomena Napolitano ◽  
Giorgia Bruno ◽  
Chiara Terracciano ◽  
Giuseppina Franzese ◽  
Nicole Piera Palomba ◽  
...  
Keyword(s):  
Pompe Disease ◽  
Rare Variants ◽  
Clinical Symptoms ◽  
Late Onset ◽  
Respiratory Muscles ◽  
Autosomal Recessive Disorder ◽  
Compound Heterozygous ◽  
Enzyme Replacement ◽  
Whole Exome ◽  
Clinical Pictures

Pompe disease is an autosomal recessive disorder caused by a deficiency in the enzyme acid alpha-glucosidase. The late-onset form of Pompe disease (LOPD) is characterized by a slowly progressing proximal muscle weakness, often involving respiratory muscles. In LOPD, the levels of GAA enzyme activity and the severity of the clinical pictures may be highly variable among individuals, even in those who harbour the same combination of GAA mutations. The result is an unpredictable genotype–phenotype correlation. The purpose of this study was to identify the genetic factors responsible for the progression, severity and drug response in LOPD. We report here on a detailed clinical, morphological and genetic study, including a whole exome sequencing (WES) analysis of 11 adult LOPD siblings belonging to two Italian families carrying compound heterozygous GAA mutations. We disclosed a heterogeneous pattern of myopathic impairment, associated, among others, with cardiac defects, intracranial vessels abnormality, osteoporosis, vitamin D deficiency, obesity and adverse response to enzyme replacement therapy (ERT). We identified deleterious variants in the genes involved in autophagy, immunity and bone metabolism, which contributed to the severity of the clinical symptoms observed in the LOPD patients. This study emphasizes the multisystem nature of LOPD and highlights the polygenic nature of the complex phenotype disclosed in these patients.

scholarly journals Expanding the genetic spectrum of primary familial brain calcification due to SLC2OA2 mutations: a case series

Neurogenetics ◽  
2021 ◽  
Author(s):  
Luca Magistrelli ◽  
Roberta Croce ◽  
Fabiola De Marchi ◽  
Chiara Basagni ◽  
Miryam Carecchio ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Case Series ◽  
Dominant Trait ◽  
Autosomal Dominant Trait ◽  
Phenotypic Spectrum ◽  
Primary Familial Brain Calcification ◽  
Psychiatric Disturbances ◽  
Brain Calcification ◽  
Uncertain Significance ◽  
Six Genes

AbstractPrimary familial brain calcification (PFBC) is a neurological condition characterized by the presence of intracranial calcifications, mainly involving basal ganglia, thalamus, and dentate nuclei. So far, six genes have been linked to this condition: SLC20A2, PDGFRB, PDGFB, and XPR1 inherited as autosomal-dominant trait, while MYORG and JAM2 present a recessive pattern of inheritance. Patients mainly present with movement disorders, psychiatric disturbances, and cognitive decline or are completely asymptomatic and calcifications may represent an occasional finding. Here we present three variants in SLC20A2, two exonic and one intronic, which we found in patients with PFBC associated to three different clinical phenotypes. One variant is novel and two were already described as variants of uncertain significance. We confirm the pathogenicity of these three variants and suggest a broadening of the phenotypic spectrum associated with mutations in SLC20A2.

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