Cholesterol levels in Fragile X syndrome

Berry‐Kravis, Elizabeth; Levin, Rebecca; Shah, Hiral; Mathur, Shaguna; Darnell, Jennifer C.; Ouyang, Bo

doi:10.1002/ajmg.a.36850

Cited by 53 publications

(46 citation statements)

References 24 publications

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“…These findings confirmed the previous reported results from a retrospective study where non-fasting lipid profile data were collected from 103 FXS North Americans (mainly were of Caucasian ethnic group) [5]. Their results showed a decrease of total cholesterol, LDL and HDL in FXS males as compared to an NHANES study population.…”

Section: Discussionsupporting

confidence: 91%

“…More specifically, low plasma cholesterol levels have been first reported in a retrospective study of 103 FXS subjects. 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].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

New insights of altered lipid profile in Fragile X Syndrome

et al. 2017

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“…We found no SLOS patients among our 79 ASD individuals, suggesting an association of ASD with other disorders of the cholesterol homeostasis. Furthermore, high incidence of hypocholesterolemia (23%) has also been reported in FXS [Berry-Kravis et al, 2015;Caku et al, 2017]. Regardless the presence of several risk factors such as ethnicity, nonobserved diet, or psychoactive treatment, the authors suggest that FXS males have lower TC, lower LDL, and higher incidence of hypocholesterolemia (23%), the same as reported from the present study when compared to the normative population [Caku et al, 2017].…”

Section: Discussionsupporting

confidence: 86%

“…TG and HDL did not correlate with BMI in ASD affected individuals, unlike in the controls which reflect the trend observed in the general population as expected [Abbasi, Blasey, & Reaven, ; Bennasar‐Veny et al, ; Shamai et al, ]. A lack of a relationship between the BMI and lipids levels has also been reported in the FXS population, suggesting that lipid metabolism is a characteristic of ASD comparable to FXS [Berry‐Kravis et al, ] where it is regulated independently of the BMI.…”

Section: Discussionsupporting

confidence: 59%

“…Lipid profile abnormalities have been recently reported in FXS with 26%-35% of individuals having total cholesterol (TC) <10th centile [Berry-Kravis et al, 2015] while more than 20% individuals fulfilling the criteria of hypocholesterolemia [Caku et al, 2017]. The latter, defined as a plasma TC level below the fifth percentile of the normal population adjusted for age, sex, and ethnic origin [Berry-Kravis et al, 2015;Elmehdawi, 2008]. [Bertone et al, 2005].…”

Section: Introductionmentioning

confidence: 99%

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Implication of hypocholesterolemia in autism spectrum disorder and its associated comorbidities: A retrospective case–control study

et al. 2019

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Autism spectrum disorder (ASD) has been associated with low cholesterol levels in a limited number of studies. However, the prevalence of hypocholesterolemia as well as the degree of association with ASD remains to be elucidated. We therefore sought to investigate the lipid profiles of a group of French‐Canadian ASD individuals. The medical records of 79 ASD individuals and 79 age and gender‐matched healthy controls were retrospectively reviewed. The fasting lipid profiles including total cholesterol (TC), high‐density lipoprotein, triglycerides, and low‐density lipoprotein were extracted for individuals of both groups along with the following clinical data: anthropometric measurements, medication use and associated disorders. Lipid parameters were compared to age and gender‐based normative population and categorized in centile groups. The prevalence of hypocholesterolemia was revealed to be more than threefold higher in ASD individuals as compared to the general population (23%; P = 0.005). The 25th centile was determined as a potential TC threshold that could best predict the ASD (odds ratio [OR] = 3.04; 95% confidence interval [CI]: 1.58–6.65; P < 0.001). This study identified specific ASD comorbidities associated with hypocholesterolemia: TC levels below the 10th centile were associated with a higher rate of ASD‐associated intellectual disability (OR = 3.33; 95% CI: 1.26–8.00) and anxiety/depression (OR = 4.74; 95% CI: 1.40–15.73). Overall, these results support a potential association between hypocholesterolemia and ASD occurrence. Application of this study to larger populations is urging to provide more extensive data that may further elucidate the association between hypocholesterolemia and ASD. Autism Res 2019, 12: 1860–1869. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary Association of autism spectrum disorder (ASD) with abnormally low levels of cholesterol (hypocholesterolemia) has been documented before. These studies were incomplete, and the conclusion remains speculative. Here, we reviewed the medical records of 79 French‐Canadian ASD individuals and compared their total cholesterol (TC) levels to healthy individuals matched for age and gender. We observed four times more hypocholesterolemia in ASD than in the general population. Furthermore, low TC in ASD was associated with higher rates of ASD‐associated intellectual disability and anxiety/depression. Our results support an association between hypocholesterolemia and ASD and open novel opportunities for the diagnosis and treatment of specific forms of ASD.

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The role of cholesterol metabolism and various steroid abnormalities in autism spectrum disorders: A hypothesis paper

et al. 2017

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Based on evidence from the relevant research literature, we present a hypothesis that there may be a link between cholesterol, vitamin D, and steroid hormones which subsequently impacts on the development of at least some of the “autisms” [Coleman & Gillberg]. Our hypothesis, driven by the peer reviewed literature, posits that there may be links between cholesterol metabolism, which we will refer to as “steroid metabolism” and findings of steroid abnormalities of various kinds (cortisol, testosterone, estrogens, progesterone, vitamin D) in autism spectrum disorder (ASD). Further research investigating these potential links is warranted to further our understanding of the biological mechanisms underlying ASD. Autism Res 2017. © 2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research. Autism Res 2017, 10: 1022–1044. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

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Cholesterol levels in Fragile X syndrome

Cited by 53 publications

References 24 publications

New insights of altered lipid profile in Fragile X Syndrome

New insights of altered lipid profile in Fragile X Syndrome

Implication of hypocholesterolemia in autism spectrum disorder and its associated comorbidities: A retrospective case–control study

The role of cholesterol metabolism and various steroid abnormalities in autism spectrum disorders: A hypothesis paper

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