The first Japanese case with familial combined hypolipidemia without any complications caused by loss-of function variants in ANGPTL3: Case report

• Published in: Heliyon 2024-04, Vol.10 (8), p.e29924, Article e29924
• Main Authors: Tada, Hayato, Kojima, Nobuko, Kawashiri, Masa-aki, Takamura, Masayuki
• Format: Article
• Language: English
• Subjects: Angiopoietin-like 3 (ANGPTL3); atherosclerosis; blood serum; Case Report; case studies; Familial hypobetalipoproteinemia (FHBL); Genetics; homozygosity; hypolipoproteinemia; LDL cholesterol; low density lipoprotein cholesterol; males; steatorrhea
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e29924

Familial combined hypolipidemia, previously known as Familial hypobetalipoproteinemia 2 (FHBL2) is considered as an extremely rare recessive disease. Here, we present the case of familial combined hypolipidemia with homozygous loss-of function (LOF) variants in angiopoietin-like protein 3 (ANGPTL3) ((NM_014495.4) c.439_442del (p.Thr146_Asn147insTer)) using panel sequencing (46 yr male whose LDL cholesterol = 34 mg/dL). The serum level of ANGPTL3 was quite low (undetectable). Despite of extreme decreasing LDL cholesterol, this case did not have any complications as hypobetalipidemia (HBL), such as steatorrhea vomiting, hematological, neuromuscular, or ophthalmological symptoms. In addition, we did not find any systemic atherosclerosis in his carotid arteries and in coronary arteries. Based on the findings suggest that inhibition of ANGPTL3 effectively reduce LDL cholesterol without any apparent side effects, although it is still unclear if he will suffer any disadvantages because of this situation in the future. •We identified the first Japanese case with familial combined hypolipidemia.•In terms of serum lipids, this condition appears to be recessive disease.•Despite extremely low LDL-C, he did not exhibit any complications associated with HBL.