Clinical features and genetic analysis of childhood sitosterolemia

Huang, Dan; Zhou, Qiong; Chao, Yunqi; Zou, Chaochun

doi:10.1097/md.0000000000015013

Cited by 17 publications

(14 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The study found that subjects with oligogenic FH had significantly higher LDL-C levels than the monogenic FH subjects, suggesting that ABCG5/ ABCG8 contributes substantially to mimicking and exacerbation of the FH phenotype 27) . Recently, there were some case reports of sitosterolemia from China 28,29) . In a recent study from China, 2 cases of sitosterolemia were identified from 208 unrelated Chinese with possible/probable or definite FH probands by a targeted genetic panel 30) .…”

Section: Sitosterolemia In Taiwanmentioning

confidence: 99%

Genetic Analysis in a Taiwanese Cohort of 750 Index Patients with Clinically Diagnosed Familial Hypercholesterolemia

Huang

Niu

Charng

2022

JAT

View full text Add to dashboard Cite

The official journal of the Japan Atherosclerosis Society and the Asian Pacific Society of Atherosclerosis and Vascular Diseases Original Article Aim: Familial hypercholesterolemia (FH) is underdiagnosed in most countries. The genetic heterogeneity of FH requires an algorithm to efficiently integrate genetic testing into clinical practice. We aimed to report the spectrum of genetic mutations from patients with clinically diagnosed FH in Taiwan.Methods: Patients with LDL-C 190 mg/dL or those with probable or definite FH according to the Taiwan Lipid Guidelines underwent genetic testing. Samples from 750 index patients from the Taiwan FH registry were screened using custom-made mass spectrometry, followed by targeted next generation sequencing (NGS) and/or multiplex ligation-dependent probe amplification (MLPA) if found negative. Results: The mean age of the patients was 52.4 15.1 years and 40.9% were male. Mutations were detected in 445 patients (59.3%). The distribution of mutations was as follows: LDLR (n 395), APOB (n 58), PCSK9 (n 0), and ABCG5 (n 3). The most common mutations were APOB c.10579 C T (p.R3527W) (12.6%), LDLR c.986 G A (p.C329Y) (11.5%), and LDLR c.1747 C T (p.H583Y) (10.8%). LDLR c.1187-10 G A (IVS 8-10) and APOB c.10580 G A (p.R3527Q) were detected using targeted NGS in Taiwan for the first time. Four novel mutations were identified, including LDLR c.1060 2 T C (IVS 7 2), LDLR c.1139 A C (p.E380A), LDLR c.1322 T C (p.A431T) c.1867 A G (p.I623V), and ABCG5 c.1337 G A (p.R447Q). Conclusion:LDLR and APOB, but not PCSK9, mutations were the major genetic causes of FH. Four novel mutations in LDLR or ABCG5 were identified. This genetic screening method using mass spectrometry, targeted NGS, and MLPA analysis provided an efficient algorithm for genetic testing for clinically diagnosed FH in Taiwan.most commonly mutated is the gene coding for lowdensity lipoprotein receptor (LDLR), resulting in defective synthesis, assembly, transport, and recycling of the LDLR. Mutations in apolipoprotein B (APOB), encoding the ligand of the LDLR, cause a phenotypically identical condition 3) . Mutations in a third gene, Proprotein Convertase Subtilisin Kexin type 9 (PCSK9), which degrades the LDLR, haveCopyright©2021 Japan Atherosclerosis Society This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.

show abstract

Section: Sitosterolemia In Taiwanmentioning

confidence: 99%

Genetic Analysis in a Taiwanese Cohort of 750 Index Patients with Clinically Diagnosed Familial Hypercholesterolemia

Huang

Niu

Charng

2022

JAT

View full text Add to dashboard Cite

show abstract

“…To expand the knowledge and reported information regarding clinical experiences related to sitosterolemia, the natural history and follow-up assays for four sitosterolemia children were traced and reported here. Literature review on clinical presentation and molecular characteristics of a total of 55 Chinese patients was conducted by collecting information from accessible databases, as well as internet sources, such as PubMed, Wiper database, Baidu Scholar, China National Knowledge Infrastructure (CNKI), and Wanfang Data [12][13][14][15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Features of chinese patients with sitosterolemia

Zhou

Su²,

Cai³

et al. 2022

Lipids Health Dis

View full text Add to dashboard Cite

Background Sitosterolemia is a lipid disorder characterized by the accumulation of phytosterols in plasma and organs, caused by mutations in the ABCG5 and/or ABCG8 genes. The disease is frequently misdiagnosed and mistreated as familial hypercholesterolemia (FH). To gain a better understanding of the disease, the current status of diagnosis and treatment of Chinese patients with sitosterolemia was reviewed and summarized. Method Literature search was performed. The clinical features and molecular characteristics of Chinese patients with sitosterolemia were analysed. Four children with sitosterolemia and the treatment experience were described. Results Fifty-five patients with sitosterolemia have been reported in China. These patients were aged from 3 months to 67 years at diagnosis, and the median was 8 years of age. Several complications, such as xanthomas in 47 patients (85%), thrombocytopenia in 17 patients (31%), anemia in 14 patients (25%), and cardiovascular damage in 12 patients (22%), were observed. Thirty-nine patients (71%) exhibited mutations in the ABCG5 gene, 15 patients (27%) showed mutations in ABCG8, and variations in both genes occurred in one patient (2%). A patient with two clinically rare diseases, namely, sitosterolemia and glycogen storage disease type VI (GSD VI)), is reported here for the first time. The four reported patients were treated with low cholesterol and phytosterol-limited diet alone or combined with cholestyramine. Even though decreases were observed for total plasma cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C), and these levels were as low as normal in some patients, the levels of plant sterols remained above the normal range. However, TC, LDL-C and plant sterol levels remained at high levels in patients treated with a control diet control only. Conclusions The analysis reveals that different from Caucasians carrying mainly variations in ABCG8, most Chinese patients have mutations in the ABCG5 gene, and Arg446Ter, Gln251Ter, anArg389His might be hot-spot mutations in Chinese patients. The current survey provides clinical data to enable the development of a standardized protocol for the diagnosis and treatment of sitosterolemia in China.

show abstract

“…The clinical features are heterogeneous and the age of presentation varies between patients, making early diagnosis challenging 4 . However, similar to our patient, dermatologic manifestation such as xanthomas may be the only presenting feature of sitosterolemia, and clinical suspicion must be high in order to recognize the condition 13 . Patients with sitosterolemia are often diagnosed as a consequence of investigations for hypercholesterolemia.…”

Section: Discussionmentioning

confidence: 49%

Dig deeper when it does not make sense: Juvenile xanthomas due to sitosterolemia

et al. 2020

View full text Add to dashboard Cite

Sitosterolemia is an extremely rare autosomal recessive disease caused by mutations in either ABCG5 or ABCG8, which encode for a sterol efflux transporter (sterolin) that pumps sterols out into the intestinal lumen or into bile. This leads to progressive accumulation of plant sterols in blood and tissues. Clinical presentation is variable and may include xanthoma, arthritis, thyroid dysfunction, premature atherosclerotic disease, splenomegaly, and hematologic manifestations. We report a child presented with multiple xanthomas at age 5.5 years, located on the elbow, knee, and toe. Juvenile xanthogranuloma was considered based on histopathologic findings. At 8 years of age, a lipid profile showed markedly elevated total cholesterol (9.4 mmol/L) and low‐density lipoprotein cholesterol (LDL‐C, 7.4 mmol/L). Simvastatin therapy was initiated, however, the lipid profile was persistently abnormal. At age 8.5 years, genetic testing identified two novel variants: (NM_022437.3[ABCG8]:c.1444del;p.Leu482Trpfs*40) and (NM_022437.3[ABCG8]:c.1640T>C;p.Leu547Pro) in the ABCG8 gene. Plasma sitosterol was subsequently found to be very high, confirming the diagnosis. She was started on a low plant sterol and cholesterol diet for 6 weeks with insignificant response and therefore ezetimibe (10 mg daily) was added. This resulted in significant reduction of cholesterol, LDL, sitosterol levels, and no further increase in the size of the xanthomas. This case emphasizes the diagnostic odyssey, the benefits of genomic testing and importance of a correct diagnosis in order to initiate appropriate therapy. It also illustrates the importance of considering rare conditions, such as sitosterolemia, as a differential diagnosis in patients with hypercholesterolemia and increased LDL‐C.

show abstract

Clinical features and genetic analysis of childhood sitosterolemia

Cited by 17 publications

References 43 publications

Genetic Analysis in a Taiwanese Cohort of 750 Index Patients with Clinically Diagnosed Familial Hypercholesterolemia

Genetic Analysis in a Taiwanese Cohort of 750 Index Patients with Clinically Diagnosed Familial Hypercholesterolemia

Features of chinese patients with sitosterolemia

Dig deeper when it does not make sense: Juvenile xanthomas due to sitosterolemia

Contact Info

Product

Resources

About