Long-term clinical evaluation of patients with alpha-mannosidosis – A multicenter study

IF 1.6 4区 医学 Q3 GENETICS & HEREDITY
Engin Köse , Çiğdem Seher Kasapkara , Aslı İnci , Yılmaz Yıldız , İlknur Sürücü Kara , Ayça Burcu Kahraman , Leyla Tümer , Ali Dursun , Fatma Tuba Eminoğlu
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Abstract

Background

Alpha mannosidosis is an autosomal recessive lysosomal storage disorder caused by biallelic pathogenic variants in the MAN2B1 gene. It manifests with clinical features, including intellectual disability, hearing impairment, coarse facial appearance, skeletal anomalies, immunodeficiency, central nervous system involvement, psychiatric comorbidities, corneal opacity, and hepatosplenomegaly.

This multicenter study assesses the long-term outcomes of individuals diagnosed with alpha-mannosidosis, examining demographic, clinical, laboratory, and molecular characteristics.

Method

Sixteen patients diagnosed with alpha-mannosidosis who presented to four pediatric metabolic units were included in the study. The patients' medical records were analyzed and data on demographics, clinical presentation and laboratory findings were recorded.

Results

Of the 16 patients (6 females, 10 males) with alpha mannosidosis included in the study, the mean age at the time of diagnosis was 79.4 ± 56.1 (16–208) months, and the mean diagnosis delay time was 57.9 ± 51.9 (4–181) months.

Hearing loss was the primary manifestation found in seven out of 16 patients (43.8%), followed by speech delay in 37.8%. On clinical follow-up, 87.5% of patients experienced recurrent infections, mainly in the upper respiratory tract, with 12 requiring the use of a hearing aid. Hepatomegaly was found in six out of 13 patients who received abdominal ultrasonography; two out of 12 patients who underwent echocardiography were found to have mitral valve prolapse (16.6%).

Upon neurological evaluation, five patients displayed no neurological manifestation. Delayed language development was observed in nine (56.3%) patients, intellectual disability in eight (50%) patients, and hypertonicity was identified in one (6.3%) patient with the severe form of the disease.

Homozygous c.2477C>A (p.Ser826Ter) and homozygous c.967G>A (p.Glu323Lys) novel variants were detected in four patients and one patient, respectively. The most common variant observed in the study was c.2477C>A (p.Ser826Ter).

Conclusion

The present study identified two novel MAN2B1 variants. An evaluation of the long-term outcome of alpha-mannosidosis, in which the early initiation of enzyme replacement therapy (ERT) may lead to a better clinical outcome, can permit a better analysis of the effect of ERT on the natural progression of the disease.

对α-甘露糖苷酶病患者的长期临床评估--一项多中心研究
阿尔法甘露糖症是一种常染色体隐性溶酶体储积症,由基因中的双倍致病变体引起。它的临床表现包括智力障碍、听力障碍、面部粗糙、骨骼异常、免疫缺陷、中枢神经系统受累、精神合并症、角膜混浊和肝脾肿大。本研究共纳入了 16 名被诊断为α-甘露糖苷酶病患者,他们曾在四个儿科代谢科就诊。研究人员对患者的病历进行了分析,并记录了有关人口统计学、临床表现和实验室检查结果的数据。在纳入研究的16名α-甘露糖苷酸病患者(6名女性,10名男性)中,确诊时的平均年龄为(79.4 ± 56.1)(16-208)个月,平均确诊延迟时间为(57.9 ± 51.9)(4-181)个月。本研究发现了两种新型变异。对α-甘露糖苷酸病的长期预后进行评估,可以更好地分析酶替代疗法对疾病自然进展的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.10
自引率
0.00%
发文量
193
审稿时长
66 days
期刊介绍: The European Journal of Medical Genetics (EJMG) is a peer-reviewed journal that publishes articles in English on various aspects of human and medical genetics and of the genetics of experimental models. Original clinical and experimental research articles, short clinical reports, review articles and letters to the editor are welcome on topics such as : • Dysmorphology and syndrome delineation • Molecular genetics and molecular cytogenetics of inherited disorders • Clinical applications of genomics and nextgen sequencing technologies • Syndromal cancer genetics • Behavioral genetics • Community genetics • Fetal pathology and prenatal diagnosis • Genetic counseling.
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