目的 探讨1例成年型球形细胞脑白质营养不良/Krabbe病(KD)患者的临床特征与遗传学病因。 方法 选取2022年2月15日因"右下肢无力进行性加重4年余"于华中科技大学同济医学院附属同济医院神经内科就诊的1例KD患者为研究对象。对患者进行临床、影像学及基因变异分析并进行家系验证。 结果 患者为36岁女性，以痉挛性步态为主要临床表现。头颅MRI示双侧皮质脊髓束走行区对称性病变，白细胞β-半乳糖脑苷脂酶(GALC)活性明显降低。患者的GALC基因存在c.461C>A(p.Pro154His)及c.1901T>C(p.Leu634Ser)复合杂合错义变异，其母亲、姐姐及外甥均携带c.461C>A(p.Pro154His)杂合变异，其父亲携带c.1901T>C(p.Leu634Ser)杂合变异。 结论 患者最终被诊断为成年型KD。GALC基因c.461C>A(p.Pro154His)及c.1901T>C(p.Leu634Ser)复合杂合变异可能是其遗传学病因。 Objective To explore the clinical features and genetic etiology of a patient with adult-onset globoid cell leukodystrophy/Krabbe disease (KD). Methods A patient who was admitted to the Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology on February 15, 2022 due to exacerbation of right leg weakness for over 4 years was selected as the study subject. Clinical data and results of medical imaging and genetic analysis were analyzed. Candidate variants were verified by family analysis. Results The patient, a 36-year-old woman, had spasmodic gait as the primary presentation. Cranial magnetic resonance imaging (MRI) revealed symmetrical abnormalities in the bilateral corticospinal tracts, and the activity of β-galactocerebrosidase (GALC) in her white blood cells was significantly decreased. The patient was found to harbor compound heterozygous variants of the GALC gene, namely c.461C>A (p.Pro154His) and c. 1901T>C (p.Leu634Ser). Her mother, sister and nephew were heterozygous carriers of the c. 461C>A (p.Pro154His) variant, whilst her father was heterozygous for the c.1901T>C (p.Leu634Ser) variant. Conclusion The patient was ultimately diagnosed with adult-onset KD, for which the compound heterozygous variants of the GALC gene may be accountable.
Genetic analysis of a case with Adult-onset globoid cell leukodystrophy
Objective To explore the clinical features and genetic etiology of a patient with adult-onset globoid cell leukodystrophy/Krabbe disease (KD). Methods A patient who was admitted to the Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology on February 15, 2022 due to exacerbation of right leg weakness for over 4 years was selected as the study subject. Clinical data and results of medical imaging and genetic analysis were analyzed. Candidate variants were verified by family analysis. Results The patient, a 36-year-old woman, had spasmodic gait as the primary presentation. Cranial magnetic resonance imaging (MRI) revealed symmetrical abnormalities in the bilateral corticospinal tracts, and the activity of β-galactocerebrosidase (GALC) in her white blood cells was significantly decreased. The patient was found to harbor compound heterozygous variants of the GALC gene, namely c.461C>A (p.Pro154His) and c. 1901T>C (p.Leu634Ser). Her mother, sister and nephew were heterozygous carriers of the c. 461C>A (p.Pro154His) variant, whilst her father was heterozygous for the c.1901T>C (p.Leu634Ser) variant. Conclusion The patient was ultimately diagnosed with adult-onset KD, for which the compound heterozygous variants of the GALC gene may be accountable.
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