Clinical, genetic profile and therapy evaluation of 55 children and 5 adults with sitosterolemia

Xia, Yu; Duan, Ying; Zheng, Wanqi; Liang, Lili; Zhang, Huiwen; Luo, Xiaomei; Gu, Xuefan; Sun, Yu; Xiao, Bing; Qiu, Wenjuan

doi:10.1016/j.jacl.2021.11.015

Cited by 15 publications

(9 citation statements)

References 35 publications

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“…The gene sequencing results suggested that nine out of ten cases were homozygous or compound heterozygous variants of the ABCG5 gene, and only one case was a compound heterozygous variant of the ABCG8 gene. This is consistent with previous reports that Caucasians often carry ABCG8 variants, while Chinese, Japanese and Indian patients tend to have ABCG5 variants [14][15][16]24, [16]. Other studies have also suggested that the most common variants of the ABCG5 gene are Arg389His and Arg419His [27,28].…”

Section: Discussionsupporting

confidence: 92%

“…Macrothrombocytopenia or hemolytic anemia with STSL has been reported in the literature [13,14,16,34,35]. Of the ten patients with STSL in this study, 50% had mild anemia.…”

Section: Discussionsupporting

confidence: 51%

“…Vascular stenosis was found in two cases (20%, 2/10) of STSL in this study, representing the early-onset cardiovascular events of STSL. Xia [16] and Tada [14] reported that 19% and 25% of STSL patients exhibited atherosclerosis, respectively. Phytosterols can penetrate the arterial wall, stimulate foam cell formation, produce proinflammatory cytokines, attract more monocytes and accelerate atherosclerosis [22].…”

Section: Discussionmentioning

confidence: 99%

“…STSL also has other major clinical manifestations, such as giant platelets with macrothrombocytopenia (reduced giant platelet count) and hemolytic anemia [12][13][14][15][16]. Therefore, this study intends to explore whether there are differences in cholesterol (Chol), low-density lipoprotein cholesterol (LDL-c), mean platelet volume (MPV), and hemoglobin (Hb) between children with STSL and FH with xanthomas as the primary clinical presentation, as well as to summarize other clinical features of STSL, to provide clues for early clinical diagnosis.…”

Section: Introductionmentioning

confidence: 99%

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Clinical characteristics of sitosterolemic children with xanthomas as the first manifestation

et al. 2022

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Background: Sitosterolemia (STSL) is an extremely rare genetic disease. Xanthomas as the first symptom are frequently misinterpreted as familial hypercholesterolemia (FH) in children. Inappropriate treatment may deteriorate the condition of STSL. Objectives: To present the clinical and laboratory characteristics of xanthomatous children diagnosed with sitosterolemia in comparison with childhood FH with xanthomas. Methods: We summarized and compared the clinical characteristics of STSL and FH patients with xanthomas as the first manifestations and investigated the different indicators between the STSL and FH groups, as well as their diagnostic values for STSL. Results: Two tertiary pediatric endocrinology departments contributed ten STSL cases. Five of the STSL patients (50%) experienced mild anemia, whereas two (20%) had vascular complications. The xanthomas of the STSL group displayed morphologies comparable to those of the FH group. There were ten cases of homozygous FH (HoFH) with xanthomas as the predominant symptom of the control group who had no anemia. The serum cholesterol (Chol) levels of the STSL and FH groups were 12.57 (9.55 ~ 14.62) mmol/L and 17.45 (16.04 ~ 21.47) mmol/L, respectively (p value 0.002). The serum low-density lipoprotein cholesterol (LDL-c) levels of the STSL and FH groups were 9.26 ± 2.71 mmol/L and 14.58 ± 4.08 mmol/L, respectively (p value 0.003). Meanwhile, the mean platelet volume (MPV) levels of the STSL and FH groups were 11.00 (9.79 ~ 12.53) fl. and 8.95 (8.88 ~ 12.28) fl., respectively (p value 0.009). The anemia proportions of the STSL and FH groups were 50% and 0%, respectively (p value 0.033). The AUC values of Chol, LDL-c, MPV, hemoglobin (Hb) for the diagnosis of STSL were 0.910, 0.886, 0.869, 0.879, respectively. Chol ≤ 15.41 mmol/L, LDL-c ≤ 13.22 mmol/L, MPV ≥ 9.05 fl., or Hb≤120 g/L were the best thresholds for diagnosing STSL with childhood xanthomas. Conclusion The xanthoma morphology of STSL patients resembles that of FH patients. Xanthomas as the initial symptom of a child with Chol ≤ 15.41 mmol/L, LDL-c≤13.22 mmol/L, MPV ≥ 9.05 fl., or Hb≤120 g/L, he was most likely to have STSL.

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Section: Discussionsupporting

confidence: 92%

“…Macrothrombocytopenia or hemolytic anemia with STSL has been reported in the literature [13,14,16,34,35]. Of the ten patients with STSL in this study, 50% had mild anemia.…”

Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical characteristics of sitosterolemic children with xanthomas as the first manifestation

et al. 2022

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“…Ampli ed fragments were sequenced using a 96-capillary 3730xl system (ABI, Foster City, California, United States). (ii) ES: ES was performed using the capture kit of the xGen Exome Research Panel (Integrated DNA Technologies, Coralville, IO, USA), as previously reported [32]. Variants at a frequency over 1% in 1000 Genomes Project, Genome Aggregation Database (GnomAD), and Exome Variant Server (EVS) or at a frequency over 5% in a local database (containing approximately 6000 exomes) were excluded from the list of candidate variants.…”

Section: Molecular Analysismentioning

confidence: 99%

Clinical, genetic profile and therapy evaluation of 11 Chinese paediatric patients with Fanconi-Bickel syndrome

Du,

Xia,

Sun

et al. 2023

Preprint

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Background: Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by impaired glucose and galactose utilization as well as proximal renal tubular dysfunction. Reported FBS data from China are scarce. Methods: Clinical, biochemical, genetic, treatment, and follow-up data for 11 paediatric patients with FBS were retrospectively analysed. Results: Hepatomegaly (10/11), short stature (10/11) and hypophosphataemic rickets (7/11) were the most common initial symptoms. At diagnosis, all patients had decreased fasting blood glucose (FBG), plasma bicarbonate (HCO3-) and serum phosphorus, as well as elevated liver transaminases, alkaline phosphatase (AKP) and proximal renal tubular dysfunction. Two infant patients were misdiagnosed with transient neonatal diabetes mellitus. After therapy with uncooked cornstarch and conventional rickets treatment, remission of hepatomegaly was observed in all patients, with significant improvements in FBG, liver transaminases, triglycerides, HCO3- and AKP (p < 0.05). At the last follow-up, 5/7 patients with elevated AKP had nephrocalcinosis. The mean height standard deviation score (Ht SDS) of eight patients with regular treatment increased from -4.1 to -3.5 (p = 0.02). Recombinant human growth hormone (rhGH) was administered to 4/9 patients, but their Ht SDS did not improve significantly (p = 0.13). Fourteen variants of the SLC2A2 gene were identified, with six being novel, among which one was recurrent: c.1217T>G (p.L406R) (allele frequency: 4/22, 18%). Patients with biallelic missense variants showed milder metabolic acidosis than those with null variants. Two of five patients from nonconsanguineous families with rare homozygous variations showed 5.3 Mb and 36.6 Mb of homozygosity surrounding the variants, respectively; a region of homozygosity (ROH) involving the entire chromosome 3 covering the SLC2A2 gene, suggesting uniparental disomy 3, was detected in one patient. Conclusions: Early diagnosis of FBS is difficult due to the heterogeneity of initial symptoms. Although short stature is a major issue of treatment for FBS, rhGH is not recommended. Patients with biallelic null variants may require alkali supplementation since urine bicarbonate loss is genetically related. ROH is a mechanism for rare homozygous variants of FBS in nonconsanguineous families.

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Genetic Aspects of Necrobiotic Xanthogranuloma

Chen,

Tang,

Hong

et al. 2024

JAMA Dermatol

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Clinical, genetic profile and therapy evaluation of 55 children and 5 adults with sitosterolemia

Cited by 15 publications

References 35 publications

Clinical characteristics of sitosterolemic children with xanthomas as the first manifestation

Clinical characteristics of sitosterolemic children with xanthomas as the first manifestation

Clinical, genetic profile and therapy evaluation of 11 Chinese paediatric patients with Fanconi-Bickel syndrome

Genetic Aspects of Necrobiotic Xanthogranuloma

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