Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Ital J Pediatr. 2024 Sep 27;50(1):191. doi: 10.1186/s13052-024-01757-z.
Imerslund-Gräsbeck syndrome (IGS) is an autosomal recessive disorder characterized by selective vitamin B12 malabsorption, resulting in vitamin B12 deficiency and impaired reabsorption of proximal tubular proteins.This case highlights a previously unidentified compound heterozygous variant in the Amnionless (AMN) gene that causes IGS syndrome and underscores the importance of long-term oral vitamin B12 replacement therapy in managing the condition.
In this retrospective analysis, we present the clinical data of a 3-year and 6-month-old female child diagnosed with IGS at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, in November 2018. The child was admitted to the hospital due to a history of anemia persisting for over a month. There was no previous significant medical history. The admission examination revealed megaloblastic anemia with proteinuria. Serum vitamin B12 levels were decreased, while folic acid and renal function were normal. The patient was diagnosed with megaloblastic anemia and started long-term oral vitamin B12 replacement therapy. Throughout the follow-up period, blood tests consistently showed normal results, while proteinuria persisted. In November 2019, the child and her parents underwent whole exome sequencing analysis, which revealed a novel compound heterozygous variant in the AMN gene: c.162 + 1G > A and c.922 C > T (p.Q308X) in the child, c.162 + 1G > A in the father, and c.922 C > T (p.Q308X) in the mother. Therefore, this child was further diagnosed with IGS.
In this case, whole exome sequencing proves to be highly practical in daily healthcare for diagnosing and refining rare or ultra-rare diseases with ambiguous phenotypes or genetic diversity. It is also valuable for prognostic evaluation and personalized management. Additionally, the oral vitamin B12 treatment demonstrated positive clinical effects for the child, offering a new option for patients unable to undergo intramuscular vitamin B12 replacement therapy.
肠病性肢端皮炎（IGS）是一种常染色体隐性疾病，其特征是选择性维生素 B12 吸收不良，导致维生素 B12 缺乏和近端肾小管蛋白吸收受损。本病例重点介绍了 Amnionless（AMN）基因中以前未识别的复合杂合变异，导致 IGS 综合征，并强调了长期口服维生素 B12 替代治疗在管理该病症中的重要性。
在这项回顾性分析中，我们介绍了一名 3 岁 6 个月大的女性患儿的临床数据，该患儿于 2018 年 11 月在中国华中科技大学同济医学院附属同济医院被诊断为 IGS。患儿因贫血持续一个月以上而入院。患儿既往无重大病史。入院检查发现巨幼细胞性贫血伴蛋白尿。血清维生素 B12 水平降低，而叶酸和肾功能正常。患者被诊断为巨幼细胞性贫血，并开始长期口服维生素 B12 替代治疗。在整个随访期间，血液检查结果一直正常，而蛋白尿持续存在。2019 年 11 月，患儿及其父母接受了全外显子组测序分析，结果显示 AMN 基因存在一种新的复合杂合变异：患儿存在 c.162+1G>A 和 c.922C>T(p.Q308X)，父亲存在 c.162+1G>A，母亲存在 c.922C>T(p.Q308X)。因此，该患儿进一步被诊断为 IGS。
在本病例中，全外显子组测序在日常医疗保健中对于诊断具有模糊表型或遗传多样性的罕见或超罕见疾病以及细化诊断具有高度实用性。它对于预后评估和个性化管理也具有价值。此外，该患儿接受口服维生素 B12 治疗的临床效果良好，为无法进行肌肉内维生素 B12 替代治疗的患者提供了新的选择。
