Atypical case of neonatal-onset Gaucher disease type 3b: A case report

IF 1.8 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports Pub Date : 2025-03-29 DOI:10.1016/j.ymgmr.2025.101211

Takanori Onuki , Kinuko Kojima , Kentaro Sawano , Nao Shibata , Yohei Ogawa , Go Hasegawa , Aya Narita , Hiromi Nyuzuki

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Abstract

Neonatal-onset Gaucher disease (nGD) is considered perinatal lethal GD, a variant of GD type 2 (GD2), and is associated with collodion skin or hydrops fetalis, hepatosplenomegaly, and involvement of central nervous system (CNS). Pulmonary involvement (PI) and lymphadenopathy (LD) are reported GD complications and have unknown incidence, pathogenesis, and response to treatments. Here, we report the case of a patient diagnosed with nGD with collodion skin who developed only mild neurological symptoms and later died in early childhood due to treatment-resistant PI and LD. A female neonate was born at 38 weeks of gestation (weight: approximately 2012 g, height: 45 cm). She had a collodion skin, hepatosplenomegaly, hemorrhagic plaques, and cholestatic liver disease at birth. She was diagnosed with GD based on decreased glucocerebrosidase enzyme activity, and genetic analysis of GBA1 revealed compound heterozygous mutations of c.1193G > T (p.Arg398Leu) and c.1265_1319del (p.Leu422fs). Intravenous enzyme replacement therapy (ERT) was initiated at the 15 days of age. At the age of 2 years and 2 months, she had a Developmental Quotient of 88 but developed horizontal gaze palsy. At 2 years 8 months of age, she developed mesenteric LD and PI because of which she failed to gain weight and developed tachypnea. She was started on oxygen therapy but died of respiratory failure and malnutrition due to PI and LD at the age of 3 years and 8 months. Pathological autopsy did not reveal the presence of Gaucher cells (GCs) in the liver, spleen, and bone marrow, but all lung macrophages had been transformed to GCs that were draining the alveoli, LD was observed in the mesenteric and mediastinal lymph nodes, and nodules of GCs were formed in bilateral kidneys. In conclusion, nGD with collodion skin is not always classified GD2. Although her phenotype may be classified as GD3b, her clinical course was like severe GD1. In addition, PI and LD are difficult to treat with adequate ERT.

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新生儿发病3b型戈谢病不典型病例1例

新生儿性戈谢病（nGD）被认为是围产期致死性GD，是GD2型（GD2）的一种变体，与皮肤胶凝或胎儿水肿、肝脾肿大和中枢神经系统（CNS）受累有关。肺受累（PI）和淋巴结病（LD）是GD的并发症，发病率、发病机制和治疗效果尚不清楚。在这里，我们报告了一例被诊断为胶质皮肤的nGD患者，该患者仅出现轻微的神经系统症状，后来因治疗难治性PI和LD而在儿童早期死亡。一名女性新生儿在妊娠38周出生（体重：约2012克，身高：45厘米）。她出生时皮肤胶凝，肝脾肿大，出血性斑块和胆汁淤积性肝病。根据葡萄糖脑苷酶活性降低诊断为GD， GBA1基因分析显示c.1193G >复合杂合突变；T （p.Arg398Leu）和c.1265_1319del （p.Leu422fs）。15日龄时开始静脉注射酶替代治疗（ERT）。在2岁零2个月时，她的发育商为88，但出现了水平凝视麻痹。在2岁8个月大时，她出现了肠系膜LD和PI，因为她的体重没有增加，并且出现了呼吸急促。她开始吸氧治疗，但在3岁零8个月时死于PI和LD引起的呼吸衰竭和营养不良。病理解剖未发现肝、脾和骨髓中存在戈歇细胞（GCs），但所有肺巨噬细胞均转化为引流肺泡的戈歇细胞，在肠系膜和纵隔淋巴结中观察到LD，双侧肾脏形成戈歇细胞结节。总之，胶质皮肤的nGD并不总是被归类为GD2。虽然她的表型可能归类为GD3b，但她的临床过程类似于严重的GD1。此外，PI和LD很难通过适当的ERT治疗。

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来源期刊

Molecular Genetics and Metabolism Reports Biochemistry, Genetics and Molecular Biology-Endocrinology

CiteScore

4.00

自引率

5.30%

发文量

105

审稿时长

33 days

期刊介绍： Molecular Genetics and Metabolism Reports is an open access journal that publishes molecular and metabolic reports describing investigations that use the tools of biochemistry and molecular biology for studies of normal and diseased states. In addition to original research articles, sequence reports, brief communication reports and letters to the editor are considered.