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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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.</p><p>This multicenter study assesses the long-term outcomes of individuals diagnosed with alpha-mannosidosis, examining demographic, clinical, laboratory, and molecular characteristics.</p></div><div><h3>Method</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p><p>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%).</p><p>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.</p><p>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).</p></div><div><h3>Conclusion</h3><p>The present study identified two novel <em>MAN2B1</em> 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.</p></div>","PeriodicalId":11916,"journal":{"name":"European journal of medical genetics","volume":"68 ","pages":"Article 104927"},"PeriodicalIF":1.6000,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1769721224000193/pdfft?md5=e070835ad551252ae75c0c87c59ce9e2&pid=1-s2.0-S1769721224000193-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Long-term clinical evaluation of patients with alpha-mannosidosis – A multicenter study\",\"authors\":\"Engin Köse , Çiğdem Seher Kasapkara , Aslı İnci , Yılmaz Yıldız , İlknur Sürücü Kara , Ayça Burcu Kahraman , Leyla Tümer , Ali Dursun , Fatma Tuba Eminoğlu\",\"doi\":\"10.1016/j.ejmg.2024.104927\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Alpha mannosidosis is an autosomal recessive lysosomal storage disorder caused by biallelic pathogenic variants in the <em>MAN2B1</em> 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.</p><p>This multicenter study assesses the long-term outcomes of individuals diagnosed with alpha-mannosidosis, examining demographic, clinical, laboratory, and molecular characteristics.</p></div><div><h3>Method</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p><p>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%).</p><p>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.</p><p>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).</p></div><div><h3>Conclusion</h3><p>The present study identified two novel <em>MAN2B1</em> variants. 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Long-term clinical evaluation of patients with alpha-mannosidosis – A multicenter study
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.
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.