Low Levels of HDL in Fragile X Syndrome Patients

Lisik, Małgorzata; Gutmajster, Ewa; Sieroń, Aleksander

doi:10.1007/s11745-015-4109-6

Cited by 19 publications

(21 citation statements)

References 16 publications

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“…Studies conducted in FXS adults reported an incidence of 53–61% for obesity/overweight [42, 49]. Males are more frequently overweight, while women tend to reach obesity [42].…”

Section: Discussionmentioning

confidence: 99%

Fragile X syndrome: a review of clinical and molecular diagnoses

et al. 2017

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BackgroundFragile X Syndrome (FXS) is the second cause of intellectual disability after Down syndrome and the most prevalent cause of intellectual disability in males, affecting 1:5000–7000 men and 1:4000–6000 women. It is caused by an alteration of the FMR1 gene, which maps at the Xq27.3 band: more than 99% of individuals have a CGG expansion (>200 triplets) in the 5′ UTR of the gene, and FMR1 mutations and duplication/deletion are responsible for the remaining (<1%) molecular diagnoses of FXS. The aim of this review was to gather the current clinical and molecular knowledge about FXS to provide clinicians with a tool to guide the initial assessment and follow-up of FXS and to offer to laboratory workers and researchers an update about the current diagnostic procedures.DiscussionFXS is a well-known condition; however, most of the studies thus far have focused on neuropsychiatric features. Unfortunately, some of the available studies have limitations, such as the paucity of patients enrolled or bias due to the collection of the data in a single-country population, which may be not representative of the average global FXS population. In recent years, insight into the adult presentation of the disease has progressively increased. Pharmacological treatment of FXS is essentially symptom based, but the growing understanding of the molecular and biological mechanisms of the disease are paving the way to targeted therapy, which may reverse the effects of FMRP deficiency and be a real cure for the disease itself, not just its symptoms.ConclusionsThe clinical spectrum of FXS is wide, presenting not only as an isolated intellectual disability but as a multi-systemic condition, involving predominantly the central nervous system but potentially affecting any apparatus. Given the relative high frequency of the condition and its complex clinical management, FXS appears to have an important economic and social burden.

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“…Studies conducted in FXS adults reported an incidence of 53–61% for obesity/overweight [42, 49]. Males are more frequently overweight, while women tend to reach obesity [42].…”

Section: Discussionmentioning

confidence: 99%

Fragile X syndrome: a review of clinical and molecular diagnoses

et al. 2017

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“…Fasting state and differences in the normative data of reference populations may account for between-study variations. Another recent study done in 23 Polish with FXS showed only a significant decrease of HDL-C [6]. However, their lipid levels were compared to a small sample size of 24 healthy males.…”

Section: Discussionmentioning

confidence: 99%

“…Basic components of a non-fasting lipid profile including total cholesterol, low-density lipoprotein cholesterol (LDL) and high density lipoprotein cholesterol (HDL) where all significantly reduced in FXS males as compared to age and gender-matched American reference population [5]. Low HDL levels have been as well reported in another prospective study of 23 Polish males with FXS in which fasting lipid profile was compared to an age matched group of 24 controls [6]. However, to the best of our knowledge no study has tried to identify the underlying factors related to hypocholesterolemia.…”

Section: Introductionmentioning

confidence: 97%

New insights of altered lipid profile in Fragile X Syndrome

et al. 2017

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BackgroundFragile X Syndrome (FXS) is the main genetic cause of autism and intellectual deficiency resulting the absence of the Fragile X Mental Retardation Protein (FMRP). Clinical picture is characterized by cognitive impairment associated with a broad spectrum of psychiatric comorbidities including autism spectrum disorders and attention-deficit/hyperactivity disorders. Some of these disorders have been associated with lipid abnormalities and lower cholesterol levels. Since lipids are important for neuronal development, we aim to investigate the lipid profile of French Canadian-FXS individuals and to identify the altered components of cholesterol metabolism as well as their association with clinical profile.MethodsAnthropometric data were collected from 25 FXS individuals and 26 controls. Lipid assessment included: total cholesterol (TC), triglycerides, LDL, HDL, ApoB, ApoA1, PCSK9, Lp(a) and lipoprotein electrophoresis. Aberrant and adaptive behaviour of affected individuals was respectively assessed by the ABC-C and ABAS questionnaires.ResultsFXS participants had a higher body mass index as compared to controls while 38% of them had TC<10th percentile. Lower levels of LDL, HDL and apoA1 were observed in FXS group as compared to controls. However, PCSK9 levels did not differ between the two groups. As expected, PCSK9 levels correlated with total cholesterol (rs = 0.61, p = 0.001) and LDL (rs = 0.46, p = 0.014) in the control group, while no association was present in the FXS group. An inverse relationship was observed between total cholesterol and aberrant behaviour as determined by ABC-C total score.ConclusionOur results showed the presence of hypocholesterolemia in French Canadian-FXS population, a condition that seems to influence their clinical phenotype. We identified for the first time a potential underlying alteration of PCSK9 function in FXS that could result from the absence of FMRP. Further investigations are warranted to better understand the association between cholesterol metabolism, PCSK9, FMRP and clinical profile.

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“…To study possible peripheral consequences of FMR1deficiency, some authors have compared the levels of serum and plasma biomarkers between FXS patients and healthy controls. Prior studies have focused on metabolic markers and have highlighted reduced levels of cholesterol [11][12][13] and abnormal abundances of the metabolic hormones leptin and adiponectin [14]. In a translational study addressing metabolic consequences of FMR1-deficiency both in a FXS mouse model and in FXS patients, we have recently shown that FXS patients display reductions in circulating glucose and increases in both free fatty acids and insulin, underlining metabolic anomalies in FXS [15].…”

Section: Intellectual Disabilitymentioning

confidence: 99%

Reduced serum levels of pro-inflammatory chemokines in fragile X syndrome

et al. 2020

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Background: Fragile X syndrome (FXS) is the most frequent cause of inherited intellectual disability and the most commonly identified monogenic cause of autism. Recent studies have shown that long-term pathological consequences of FXS are not solely confined to the central nervous system (CNS) but rather extend to other physiological dysfunctions in peripheral organs. To gain insights into possible immune dysfunctions in FXS, we profiled a large panel of immune-related biomarkers in the serum of FXS patients and healthy controls. Methods: We have used a sensitive and robust Electro Chemi Luminescence (ECL)-based immunoassay to measure the levels of 52 cytokines in the serum of n = 25 FXS patients and n = 29 healthy controls. We then used univariate statistics and multivariate analysis, as well as an advanced unsupervised clustering method, to identify combinations of immune-related biomarkers that could discriminate FXS patients from healthy individuals. Results: While the majority of the tested cytokines were present at similar levels in FXS patients and healthy individuals, nine chemokines, CCL2, CCL3, CCL4, CCL11, CCL13, CCL17, CCL22, CCL26 and CXCL10, were present at much lower levels in FXS patients. Using robust regression, we show that six of these biomarkers (CCL2, CCL3, CCL11, CCL22, CCL26 and CXCL10) were negatively associated with FXS diagnosis. Finally, applying the K-sparse unsupervised clustering method to the biomarker dataset allowed for the identification of two subsets of individuals, which essentially matched the FXS and healthy control categories. Conclusions: Our data show that FXS patients exhibit reduced serum levels of several chemokines and may therefore exhibit impaired immune responses. The present study also highlights the power of unsupervised clustering methods to identify combinations of biomarkers for diagnosis and prognosis in medicine.

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Low Levels of HDL in Fragile X Syndrome Patients

Cited by 19 publications

References 16 publications

Fragile X syndrome: a review of clinical and molecular diagnoses

Fragile X syndrome: a review of clinical and molecular diagnoses

New insights of altered lipid profile in Fragile X Syndrome

Reduced serum levels of pro-inflammatory chemokines in fragile X syndrome

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