Instituto da Criança, Hospital das Clínicas, Unidade de Gastroenterologia, Hepatologia e Nutrologia Pediátrica, São Paulo, SP, Brazil.
Hospital Menino Jesus, Departamento de Hepatologia Pediátrica, São Paulo, SP, Brazil.
J Pediatr (Rio J). 2019 Sep-Oct;95(5):552-558. doi: 10.1016/j.jped.2018.05.016. Epub 2018 Jul 3.
To describe the demographic, clinical, laboratory and molecular characteristics of patients with lysosomal acid lipase deficiency.
A retrospective review of the medical records of children with the disease.
Seven children with lysosomal acid lipase deficiency (5 male; 2 female); 6 were mixed race, and 1 was black. The mean ages at the first onset of symptoms and at diagnosis were 5.0 years (4 months to 9 years) and 6.9 years (3-10 years), respectively. Symptom manifestations at onset were: 3 patients had abdominal pain, one had bone/joint pain due to rickets, and 1 had chronic diarrhea and respiratory insufficiency due to interstitial pneumonitis. One was asymptomatic, and clinical suspicion arose due to hepatomegaly. Six patients had hepatomegaly, and none had splenomegaly. Two patients were siblings. Enzymatic assay and molecular analysis confirmed the diagnoses. Genetic analysis revealed a rare pathogenic variant (p.L89P) in three patients, described only once in medical literature and never described in Brazil. None of those patients were related to each other. Lysosomal acid lipase deficiency was previously described as an autosomal recessive disease, but three patients were heterozygous and undoubtedly had the disease (low enzyme activity, suggestive lab findings and clinical symptoms).
This case series supports that lysosomal acid lipase deficiency can present with highly heterogeneous signs and symptoms among patients, but it should be considered in children presenting with gastrointestinal symptoms associated with dyslipidemia. We describe a rare variant in three non-related patients that may suggest a Brazilian genotype for lysosomal acid lipase deficiency.
描述溶酶体酸性脂肪酶缺乏症患者的人口统计学、临床、实验室和分子特征。
回顾性分析患有该疾病的儿童的病历。
7 名溶酶体酸性脂肪酶缺乏症患儿（5 男；2 女）；6 名混血儿，1 名黑人。首次出现症状和确诊时的平均年龄分别为 5.0 岁（4 个月至 9 岁）和 6.9 岁（3-10 岁）。发病时的症状表现为：3 名患者有腹痛，1 名因佝偻病有骨/关节痛，1 名因间质性肺炎有慢性腹泻和呼吸功能不全。1 名无症状，因肝肿大而引起临床怀疑。6 名患者有肝肿大，无一例脾肿大。2 名患者是兄弟姐妹。酶活性测定和分子分析证实了诊断。基因分析显示 3 名患者存在罕见的致病性变异（p.L89P），该变异仅在一次医学文献中描述过，在巴西从未描述过。这些患者彼此之间没有关系。溶酶体酸性脂肪酶缺乏症以前被描述为常染色体隐性疾病，但 3 名患者为杂合子，无疑患有该病（酶活性低、有提示性实验室发现和临床症状）。
本病例系列研究表明，溶酶体酸性脂肪酶缺乏症患者的表现具有高度异质性，但应考虑到出现与血脂异常相关的胃肠道症状的儿童。我们在 3 名无亲缘关系的患者中描述了一种罕见的变异，这可能提示巴西存在溶酶体酸性脂肪酶缺乏症的基因型。
