Clinical characteristics of sitosterolemic children with xanthomas as the first manifestation

Abstract

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.

Gene variants and clinical characteristics of children with sitosterolemia

“…According to certain research, a juvenile gut may absorb cholesterol at a greater rate than an adult intestine [ 8 ]. Sitosterolemia in children can cause mainly xanthomas [ 9 ], mildly increased cholesterol and LDL-C levels, premature atherosclerotic disease, macrothrombocytopenia, or anemia. There have also been reports of other rare signs, such as growth retardation and thyroid dysfunction, arthritis, liver disease (hepatosplenomegaly with aberrant hepatic function) and cardiac disease [ 10 , 11 ].…”

Gene mutations and clinical features of pediatric sitosterolemia

“…Some studies have shown that the immature intestine may absorb higher amounts of cholesterol than adults [8]. Children with sitosterolemia may be asymptomatic or can mainly manifest as xanthoma [9], slightly elevated cholesterol and LDL-C, premature atherosclerotic disease, and blood system disease (e.g., macrothrombocytopenia, anemia). Other uncommon manifestations, including liver disease (hepatosplenomegaly with abnormal hepatic function), heart disease, arthritis, growth retardation and thyroid dysfunction, have also been reported [10,11].…”