作者
Peng‐Yu Chen,Yuan‐Yu Hong,Helen V. New,Zhuangli Tang,Sui‐Qing Cai
摘要
The case presented in "Extensive yellowish masses in bilateral orbit and neck" describes a patient with necrobiotic xanthogranuloma (NXG) without paraproteinemia,1 which closely resembles the disease pattern we have observed in three previously reported NXG cases.2 These patients, besides the characteristic periorbital lesions, often present with thrombocytopenia, anemia, splenomegaly, and a history of splenectomy due to misdiagnosis, with this procedure usually showing limited improvement in hematological abnormalities. Additional features include liver dysfunction, cirrhosis, elevated globulin levels without paraproteinemia (all four cases lacked paraproteinemia1, 2), and positive antinuclear antibodies. Findings from peripheral blood smears often reveal marked stomatocytosis and macrothrombocytosis (Figure 1). Genetic testing identifies homozygous or compound heterozygous variants in the adenosine triphosphate–binding cassette subfamily G member 5 (ABCG5; OMIM 605459) or ABCG8 (OMIM 605460) genes, confirming a diagnosis of sitosterolemia (OMIM 210250). Family histories may be negative because of the often subclinical nature of ABCG5/G8 variants in carriers. Based on this pattern, we strongly suspect that this reported patient1 may also have sitosterolemia. Sitosterolemia is an autosomal recessive sterol storage disorder characterized by markedly elevated plasma plant sterol levels due to ABCG5/G8 variants.3 Clinically, the disorder manifests primarily as xanthomas, macrothrombocytopenia, anemia, arthralgia, and premature atherosclerosis.3 Because of the limited availability of plasma plant sterol testing, diagnostic clues can often be found on peripheral blood smears showing stomatocytosis and macrothrombocytosis. Genetic testing for ABCG5/G8 variants is essential for diagnosis. Given the patient's demise,1 we recommend genetic testing of the family members to confirm our hypothesis and guide future therapeutic interventions. Our findings suggest the existence of at least two phenotypic subtypes of NXG. The classic subtype commonly coexists with paraproteinemia, plasma cell dyscrasia, or other lymphoproliferative disorders. To date, only one classic NXG case has been reported to have undergone whole-exome sequencing, which was negative, and paraproteinemia developed during follow-up.4, 5 The second subtype is associated with ABCG5/G8 variants and features a disease pattern linked to sitosterolemia, typically without paraproteinemia or hematologic malignancy. Additional cases and longer follow-up are needed to confirm this distinction. None declared.