Psychiatric and cognitive profile in Anderson‐Fabry patients: a preliminary study

Segal, Perri; Kohn, Yoav; Pollak, Yehuda; Altarescu, Gheona; Galili-Weisstub, Esti; Raas‐Rothschild, Annick

doi:10.1007/s10545-010-9133-3

Cited by 24 publications

(36 citation statements)

References 46 publications

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“…Samples available for clinical cognitive assessments have been small, spanning a broad age spectrum. While some researchers have found a pattern of below average scores in discrete cognitive abilities (Elstein et al 2012), others have found no pattern of deficits (Segal et al 2010;Low et al 2007). …”

Section: Introductionmentioning

confidence: 99%

“…Reports of cognitive difficulties are not uncommon among persons with FD (Segal et al 2010;Low et al 2007), but assessment of cognitive function has been limited. Samples available for clinical cognitive assessments have been small, spanning a broad age spectrum.…”

Section: Introductionmentioning

confidence: 99%

“…White matter changes also are important findings; however, to date, the relation of brain abnormalities to described minor changes in cognitive function in FD is not compelling (Moore et al 2007;Muller et al 2005;Schermuly et al 2011;Fellgiebel et al 2012). Chronic distress associated with FD may have more influence on cognitive function than do pathologic alterations in the central nervous system (Segal et al 2010;Schermuly et al 2011).…”

Section: Introductionmentioning

confidence: 99%

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Cognitive Function in Adults Aging with Fabry Disease: A Case–Control Feasibility Study Using Telephone-Based Assessments

et al. 2014

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We examined the feasibility of recruiting US adults !45 years old with Fabry disease (FD) for telephone assessments of cognitive functioning. A case-control design matched each FD participant on age, sex, race, and education to four participants from a populationbased study. Fifty-four participants with FD age 46-72 years were matched to 216 controls. Standardized cognitive assessments, quality of life (QOL), and medical histories were obtained by phone, supplemented by objective indices of comorbidities. Normalized scores on six cognitive tasks were calculated. On the individual tasks, scores on list recall and semantic fluency were significantly lower among FD participants (p-values < 0.05), while scores on the other four tasks did not differ. After averaging each participant's normalized scores to form a cognitive composite, we examined group differences in composite scores, before and after adjusting for multiple covariates using generalized estimating equations. The composite scores of FD cases were marginally lower than controls before covariate adjustments (p ¼ 0.08). QOL and mental health variables substantially attenuated this finding (p ¼ 0.75), highlighting the influence of these factors on cognition in FD. Additional adjustment for cardiovascular comorbidities, kidney function, and stroke had negligible impact, despite higher prevalence in the FD sample. Telephonebased cognitive assessment methods are feasible among adults with FD, affording access to a geographically dispersed sample. Although decrements in discrete cognitive domains were observed, the overall cognitive function of older adults with FD was equivalent to that of well-matched controls before and after accounting for multiple confounding variables.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cognitive Function in Adults Aging with Fabry Disease: A Case–Control Feasibility Study Using Telephone-Based Assessments

et al. 2014

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“…In a multicentre genetic screening study evaluating the frequency of NP-C among patients who shared common neurological and psychiatric symptoms, only three of 256 adults (1.2%) were confirmed to be NP-C [7]. In the literature NP-C has been misdiagnosed as Wilson disease [8] and Gaucher disease [9]. Generally, there was a long lag time between the initial onset of neurological manifestations and definite diagnosis [10].…”

Section: Introductionmentioning

confidence: 99%

Diagnosis of Niemann-Pick disease type C with 7-ketocholesterol screening followed by NPC1/NPC2 gene mutation confirmation in Chinese patients

Zhang

Wang

Lin

et al. 2014

Orphanet J Rare Dis

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BackgroundIt has been reported that oxidation product of cholesterol, 7-ketocholesterol, increases in plasma of patients with NP-C. Previously, we established a rapid test to determine the plasma 7-ketocholesterol level and found it elevated significantly in patients with acid sphingomyelinase deficient NPD and NP-C disease.MethodsIndividuals randomly referred to our outpatient clinics in the past two years for hepatosplenomegaly or isolated splenomegaly, who have been excluded as acid sphingomyelinase deficient NPD or Gaucher disease, and individuals with newborn cholestasis, psychomotor regression/retardation, were screened for plasma 7-ketocholesterol level. Individuals with high 7-ketocholesterol level were then analyzed for NPC1 and NPC2 gene mutation to confirm the accuracy of NP-C diagnosis.ResultsBy screening the plasma 7-ketocholesterol of suspect individuals, 12 out of 302 (4%) had shown remarkable high levels compared with reference. All these twelve individuals were subsequently confirmed to be NP-C by DNA analysis of NPC1 and NPC2 genes, with the early infantile form (n = 7), the late infantile form (n = 1), the juvenile form (n = 1) and the adult form (n = 1). Furthermore, two NP-C patients without observable neuropsychiatric disability were picked up through this procedure. Only one patient had NP-C due to NPC2 gene mutations, with the rest due to NPC1 gene mutations. We found that in NP-C patients AST was usually mildly elevated and ALT was in a normal range when jaundice was not present. In total, 22 mutant alleles were identified in the NPC1 gene, including six novel small deletions/insertions, e.g., c.416_417insC, c.1030delT, c.1800delC, c.2230_2231delGT, c.2302_2303insG, and c.2795dupA; seven novel exonic point mutations, c.1502A>T (p.D501V), c.1553G>A (p.R518Q), c.1832A>G (p.D611G), c.2054T>C (p.I685T), c.2128C>T(p.Q710X), c.2177G>C (p.R726T), c.2366G>A (p.R789H), and one novel intronic mutation c.2912-3C>G. Small deletions/insertions constituted nearly half of the mutant alleles (10/22, 45%), indicating a unique mutation spectrum in this cohort of Chinese NP-C patients.ConclusionOur data confirm in a clinical setting that screening plasma 7-ketocholesterol is an efficient and practical diagnostic tool to identify NP-C patients from suspect individuals. Patients without neuropsychological involvement could also be identified by this method therefore allowing an opportunity for earlier treatment.

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“…Some authors [78] investigated neuropsychological and psychiatric function in AFD patients. They studied 16 AFD patients, aged 7 to 61 years.…”

Section: Psychiatric and Cognitive Dysfunction And Functional Involvementioning

confidence: 99%

Neurological Complications of Anderson-Fabry Disease

Tuttolomondo

Pecoraro²,

Simonetta³

et al. 2013

CPD

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Characteristic clinical manifestations of AFD such as acroparesthesias, angiokeratoma, corneal opacity, hypo/ and anhidrosis, gastrointestinal symptoms, renal and cardiac dysfunctions can occur in male and female patients, although heterozygous females with AFD usually seem to be less severely affected. The most prominent CNS manifestations consist of cerebrovascular events such as transient ischaemic attacks (TIAs) and (recurrent) strokes. For the most part, CNS complications in AFD have been attributed to cerebral vasculopathy, including anatomical abnormalities. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial accumulation of Gb-3. White matter lesions (WML) on occur MRI. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. Stroke in Anderson-Fabry disease study of 721 patients with cryptogenic stroke, aged 18-55 years, showed a high prevalence of Fabry disease in this group: 5% (21/432) of men and 3% (7/289) of women. Combining results of both sexes showed that 4% of young patients with stroke of previously unknown cause had Fabry disease, corresponding to about 1-2% of the general population of young stroke patients. Cerebral micro- and macro-vasculopathy have been described in Fabry disease. Neuronal globotriaosylceramide accumulation in selective cortical and brain stem areas including the hippocampus has been reported by autopsy studies in FD, but clinical surrogates as well as the clinical relevance of these findings have not been investigated so far. Another Neurologic hallmark of Fabry disease (FD) includes small fiber neuropathy as well as cerebral micro- and macroangiopathy with premature stroke. Cranial MRI shows progressive white matter lesions (WML) at an early age, increased signal intensity in the pulvinar, and tortuosity and dilatation of the larger vessels. Conventional MRI shows a progressive load of white matter lesions (WMLs) due to cerebral vasculopathy in the course of FD. Another study has been conducted to quantify brain structural changes in clinically affected male and female patients with FD. The peripheral neuropathy in Fabry disease manifests as neuropathic pain, reduced cold and warm sensation and possibly gastrointestinal disturbances. Patients with Fabry disease begin having pain towards the end of the first decade of life or during puberty. Children as young as 6 years of age have complained of pain often associated with febrile illnesses with reduced heat and exercise tolerance. The patients describe the pain as burning that is often associated with deep ache or paresthesiae. Some patients also have joint pain. A high proportion of patients with Fabry disease is at increased risk of developing neuropsychiatric symptoms, such as depression and neuropsychological...

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Psychiatric and cognitive profile in Anderson‐Fabry patients: a preliminary study

Cited by 24 publications

References 46 publications

Cognitive Function in Adults Aging with Fabry Disease: A Case–Control Feasibility Study Using Telephone-Based Assessments

Cognitive Function in Adults Aging with Fabry Disease: A Case–Control Feasibility Study Using Telephone-Based Assessments

Diagnosis of Niemann-Pick disease type C with 7-ketocholesterol screening followed by NPC1/NPC2 gene mutation confirmation in Chinese patients

Neurological Complications of Anderson-Fabry Disease

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