Sitosterolemia Presenting With Severe Hypercholesterolemia and Intertriginous Xanthomas in a Breastfed Infant: Case Report and Brief Review

Park, Joong Heum; Chung, In Hyuk; Kim, Dong Hyun; Choi, Man Ho; Garg, Abhimanyu; Yoo, Eun-Gyong

doi:10.1210/jc.2013-3274

Cited by 47 publications

(54 citation statements)

References 28 publications

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“…Park et al also reported a similar case to ours, in which a 15-month-old girl whose severe hypercholesterolaemia (serum LDL-C level, 540 mg/dl) was also complicated by intertriginous xanthomas during breastfeeding; her hypercholesterolaemia disappeared two months after the introduction of a low-fat/low-cholesterol diet and cholestyramine. She was diagnosed with compound heterozygous sitosterolaemia due to an ABCG5 gene mutation (Park et al 2014). Our findings of greatly reduced serum cholesterol levels seen after weaning in four infantile sitosterolaemic cases reinforce the previous findings (Table 1).…”

Section: Discussionsupporting

confidence: 90%

“…Although several papers have suggested the association between sitosterolaemia and haematologic abnormalities, such as macrothrombocytopaenia, haemolytic anaemia and splenomegaly (Park et al 2014;Wang et al 2014), none of our cases exhibited any abnormal haematological manifestations.…”

Section: Resultscontrasting

confidence: 80%

“…In addition, we identified another mutation in exon 9 (c.1306G>A or p.Arg389His, Fig. 1e), which is one of the most common mutations in Asian sitosterolaemic cases (Park et al 2014). We confirmed the same mutations in Case 2 (the younger sister of Case 1).…”

Section: Resultssupporting

confidence: 64%

“…Clinical and Laboratory Characteristics of Infantile Cases with Sitosterolaemia (Table 1) We have summarised clinical and laboratory characteristics of infantile cases with sitosterolaemia of ours and those from the literature (Niu et al 2010;Park et al 2014;Rios et al 2010) in Table 1, focusing on the changes in clinical manifestations before and after the weaning. Most of the infantile cases with sitosterolaemia exhibited intertriginous xanthomas associated with extremely high LDL cholesterolaemia during breastfeeding, which decreased dramatically after weaning.…”

Section: Resultsmentioning

confidence: 99%

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Infantile Cases of Sitosterolaemia with Novel Mutations in the ABCG5 Gene: Extreme Hypercholesterolaemia is Exacerbated by Breastfeeding

et al. 2015

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Few data exists regarding the clinical impact of breastfeeding in infantile sitosterolaemic cases. We report four Japanese infantile cases of sitosterolaemia, an extremely rare inherited disease characterised by increased serum levels of plant sitosterol, presenting with severe hypercholesterolaemia and systemic xanthomas exacerbated by breastfeeding. In these four cases, genetic analyses were performed for low-density lipoprotein (LDL) receptor, proprotein convertase subtilisin/kexin type 9 (PCSK9), LDL receptor adaptor protein 1 and ATP-binding cassette (ABC) subfamily G member 5 and 8 (ABCG5 and ABCG8) genes. We assessed their clinical manifestations, including responsiveness to a variety of treatments, especially to weaning from breastfeeding and use of ezetimibe. Two pairs of mutations in the ABCG5 gene in each case, including two novel mutations (c.130C>T or p.Ser44Ala and c.1813_1817delCTTTT or p.Pro558GlufsX14) and two known mutations (c.1306G>A or p.Arg389His and c.1336C>T or p.Arg446X), were identified. Significant reductions in cholesterol levels were obtained by means of weaning from breastfeeding alone. Substantial reductions in sitosterol levels, without any apparent side effects, were observed with ezetimibe. In conclusion, we have identified infantile Japanese sitosterolaemic subjects with extreme hypercholesterolaemia exacerbated by breastfeeding. Their unique response to weaning from breastfeeding, as well as to use of ezetimibe, could provide insights into the metabolic basis of sterols in humans.

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Section: Discussionsupporting

confidence: 90%

Section: Resultscontrasting

confidence: 80%

Section: Resultssupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

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Infantile Cases of Sitosterolaemia with Novel Mutations in the ABCG5 Gene: Extreme Hypercholesterolaemia is Exacerbated by Breastfeeding

et al. 2015

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“…10,11 The condition should be considered even when consumption of plant sterols has not commenced, as phytosterols can be found in breast milk. 12 …”

Section: Clinical Sensitivity (Proportion Of Positive Tests If the DImentioning

confidence: 99%

Clinical utility gene card for: Sitosterolaemia

et al. 2016

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Compound heterozygous mutations in ABCG5 or ABCG8 causing Chinese familial Sitosterolemia

Sun¹,

Zhang

et al. 2020

The Journal of Gene Medicine

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BackgroundSitosterolemia (STSL), also known as phytosterolemia, is a rare autosomal recessive hereditary disease caused by mutations in the ABCG5 or ABCG8 genes. The disease is a result of disorders in lipoprotein metabolism, and is characterized by tendinous and tuberous xanthomas, elevated plasma cholesterol and phytosterol levels, and thrombocytopenia and hemolytic anemia in several patients. The manifestations of STSL are diverse and can easily be misdiagnosed. In recent years, cases of this disease in children have been reported in succession. There is therefore a need for clinicians to improve identification of STSL and perform early intervention.MethodsWe evaluated four children with STSL caused by genetic mutations in ABCG5 or ABCG8, as well as their family members, by analyzing their clinical characteristics and performing Trio‐whole exome sequencing. The biological consequences of the mutations were analyzed using various bioinformatics software. We also analyzed the consequences of a mutation commonly observed in STSL patients on the structure of the protein involved.ResultsWe identified five previously unreported pathogenic mutations of different phenotypes of STSL: ABCG5 NM_022436:c.1337G>A; ABCG8 NM_022437:c.965‐1G>A, c.323‐1G>C, c.1418C>G and c.1534G>A. We also report the structural changes brought about by a mutation common in STSL patients, as well as the possible consequences of these changes.ConclusionsOur findings further broaden the genotypic and phenotypic profiles of the onset of STSL in the pediatric population and provide information for the diagnosis and treatment of this disease.

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Sitosterolemia Presenting With Severe Hypercholesterolemia and Intertriginous Xanthomas in a Breastfed Infant: Case Report and Brief Review

Abstract: Our case suggests that sitosterolemia can present with severe hypercholesterolemia and intertriginous xanthomas. Sitosterolemia should be suspected when a patient with hypercholesterolemia shows unexpectedly good response to dietary modification or bile acid sequestrant therapy.

Cited by 47 publications

References 28 publications

Infantile Cases of Sitosterolaemia with Novel Mutations in the ABCG5 Gene: Extreme Hypercholesterolaemia is Exacerbated by Breastfeeding

Infantile Cases of Sitosterolaemia with Novel Mutations in the ABCG5 Gene: Extreme Hypercholesterolaemia is Exacerbated by Breastfeeding

Clinical utility gene card for: Sitosterolaemia

Compound heterozygous mutations in ABCG5 or ABCG8 causing Chinese familial Sitosterolemia

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