Nöropsikiyatrik semptomlarla başvuran mukopolisakkaridoz olguları
Öz
Amaç: Mukopolisakkaridozlar (MPS); glukozaminoglikanların (GAG) lizozom içerisinde yıkılamaması sonucu çoklu sistem tutulumlarına neden olan heterojen bir hastalık grubudur. MPS II ve III’ de santral sinir sistemi tutulumu daha ön plandadır. Erken dönemde bilişsel gerilik, davranış problemleri, ilerleyici davranış-uyku problemleri, gecikmiş konuşma, otizm benzeri bulgular, sebebi bilinmeyen zihinsel yetersizlik görülebilir.
Gereç ve Yöntem: Mukopolisakkaridoz II ve III tanısı ile izlenen nöbet, gelişim basamaklarında gerilik, konuşma gecikmesi, nörolojik gelişim basamaklarında kayıp gibi nöropsikiyatrik semptomlarla başvuran hastaların sonuçları retrospektif olarak kaydedildi.
Bulgular: Çalışmaya 11 olgu dahil edildi. 6 (%54,5)’sı erkek, 5 (%45,5)’i kadındı. MPS III olgularının 4 (%50)’ü MPS 3A, 3 (%37,5)’ü MPS IIIB, 1 (%12,5)’i MPS IIIC tanılıdır. Başvuruda 6 (%54,5)’sinde konuşma geriliği, 2 (%18,1)’ i bilişsel gerilik, 3 (%27,2)’ sinin ise hiperaktivite varken ek olarak 9 (%81,8)’inde motor gerilik de eşlik etmekteydi. Başvuru yaş ortalamaları 8,4 (±5,2 SDS) yıldı. 6 (%54,5)’sı fizik tedavi rehabilitasyon ve özel eğitim desteği almaktaydı.
Sonuç: Nöropsikiyatrik semptomlarla başvuran hastalarda mukopolisakkaridozların da düşünülerek, İdrar GAG, enzimatik ve gereğinde genetik analizlerin yapılması, erken teşhis ve tedavi açısından önemlidir.
Anahtar Kelimeler
Mukopolisakkaridoz Hiperaktivite Konuşma geriliği Bilişsel gerilik
Kaynakça
- Barone R, Pellico A, Pittalà A, Gasperini S. Neurobehavioral phenotypes of neuronopathic mucopolysaccharidoses. Italian Journal of Pediatrics. 2018;44(2):107-15.
- Okuyama T, Eto Y, Sakai N, Minami K, Yamamoto T, Sonoda H, et al. Iduronate-2-Sulfatase with Anti-human Transferrin Receptor Antibody for Neuropathic Mucopolysaccharidosis II: A Phase 1/2 Trial. Mol Ther. 2019;27(2):456-64.
- Wijburg FA, Whitley CB, Muenzer J, Gasperini S, Del Toro M, Muschol N, et al. Intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A: A phase IIb randomized trial. Mol Genet Metab. 2019;126(2):121-30.
- Değerliyurt A, Yayıcı Köken Ö, Teker ND, Aktaş D. Significant neuropsychiatric symptoms: three mucopolysaccharidosis type IIIB cases, two of whom were siblings with a novel NAGLU gene mutation. Neurocase. 2021:1-6.
- Sampayo-Cordero M, Miguel-Huguet B, Pardo-Mateos A, Malfettone A, Perez-Garcia J, Llombart-Cussac A, et al. Agreement between results of meta-analyses from case reports and clinical studies, regarding efficacy and safety of idursulfase therapy in patients with mucopolysaccharidosis type II (MPS-II). A new tool for evidence-based medicine in rare diseases. Orphanet J Rare Dis. 2019;14(1):230.
- Abreu NJ, Selvaraj B, Truxal KV, Moore-Clingenpeel M, Zumberge NA, McNally KA, et al. Longitudinal MRI brain volume changes over one year in children with mucopolysaccharidosis types IIIA and IIIB. Molecular Genetics and Metabolism. 2021;133(2):193-200.
- Ergun P, Kagnıcı M, Ucar S, Coker M, Akcay Y, Sozmen E. Possible diagnostic markers for Mucopolysaccharidoses; Cathepsin-D, Galectin-3 and Chitotriosidase. IZMIR DR BEHCET UZ COCUK HASTANESI DERGISI. 2017;7(2).
- Escolar M, Bradshaw J, Byers VT, Giugliani R, Golightly L, Lourenço CM, et al. Development of a Clinical Algorithm for the Early Diagnosis of Mucopolysaccharidosis III. Journal of Inborn Errors of Metabolism and Screening. 2020;8.
- Ghosh A, Rust S, Langford-Smith K, Weisberg D, Canal M, Breen C, et al. High dose genistein in Sanfilippo syndrome: A randomised controlled trial. J Inherit Metab Dis. 2021;44(5):1248-62.
- Seker Yilmaz B, Davison J, Jones SA, Baruteau J. Novel therapies for mucopolysaccharidosis type III. Journal of Inherited Metabolic Disease. 2021;44(1):129-47.
- Yazici H, Canda E, Er E, Ucar S, Onay H, Ozkinay F, et al. Clinical, biochemical and molecular characteristics of fifteen patients with mucopolysaccharidosis type II in Western Turkey. JOURNAL OF PEDIATRIC RESEARCH. 2018;5(1).
- Wolfenden C, Wittkowski A, Jones SA, Rust S, Hare DJ. Autism spectrum disorder symptomatology in children with mucopolysaccharide disease type III. British Journal of Learning Disabilities. 2019;47(1):5-11.
- Hoffmann F, Hoffmann S, Kunzmann K, Ries M. Challenging behavior in mucopolysaccharidoses types I–III and day-to-day coping strategies: a cross sectional explorative study. Orphanet journal of rare diseases. 2020;15(1):1-14.
- Ucar SK, Ozbaran B, Demiral N, Yuncu Z, Erermis S, Coker M. Clinical overview of children with mucopolysaccharidosis type III A and effect of Risperidone treatment on children and their mothers psychological status. Brain and Development. 2010;32(2):156-61.
- Scarpa M, Lourenço CM, Amartino H. Epilepsy in mucopolysaccharidosis disorders. Molecular genetics and metabolism. 2017;122:55-61.
A retrospective study on neuropsychiatric presentations of mucopolysaccharidoses
Öz
Aim: Mucopolysaccharidoses (MPS) are a heterogeneous group of diseases characterised by systemic manifestations due to impaired glucosaminoglycans (GAG) degradation within lysosomes. Mucopolysaccharidosis type II (MPS II, Hunter) is a lysosomal disease caused by mutations in the iduronate-sulfatase (IDS) gene. MPS II is inherited in an X-linked recessive manner. Mucopolysaccharidosis type III (MPS III, Sanfilippo) is an autosomal recessive lysosomal disease. It has four subtypes (A, B, C, and D). MPS II and III particularly exhibit significant central nervous system involvement. Early clinical manifestations may include cognitive delay, behavioural disturbances, progressive behaviour-sleep problems, delayed speech, autism-like features, and unexplained intellectual disability.
Materials and Methods: In this retrospective study, we recorded the clinical findings of patients who were diagnosed with mucopolysaccharidosis type II and III and presented with neuropsychiatric symptoms such as seizures, developmental delay, speech impairment, and loss of neurological milestones.
Results: The study included eleven cases, comprising 6 (54.5%) males and 5 (45.5%) females. Among them, 4 (50%) were diagnosed with MPS IIIA, 3 (37.5%) with MPS IIIB, and 1 (12.5%) with MPS IIIC. Six patients (54.5%) had speech delay, while two (18.1%) had cognitive delay, and three (27.2%) had hyperactivity, with nine (81.8%) experiencing motor delay. The mean age at presentation was 8.4 (±5.2 SD) years, with six patients (54.5%) receiving physical therapy and special training.
Conclusion: In patients presenting with neuropsychiatric symptoms, consideration of mucopolysaccharidoses along with urine GAG, enzymatic assays and, when indicated, genetic testing is crucial for early diagnosis and intervention.
Anahtar Kelimeler
Mucopolysaccharidoses Hyperactivity Speech impairment Cognitive impairment
Kaynakça
- Barone R, Pellico A, Pittalà A, Gasperini S. Neurobehavioral phenotypes of neuronopathic mucopolysaccharidoses. Italian Journal of Pediatrics. 2018;44(2):107-15.
- Okuyama T, Eto Y, Sakai N, Minami K, Yamamoto T, Sonoda H, et al. Iduronate-2-Sulfatase with Anti-human Transferrin Receptor Antibody for Neuropathic Mucopolysaccharidosis II: A Phase 1/2 Trial. Mol Ther. 2019;27(2):456-64.
- Wijburg FA, Whitley CB, Muenzer J, Gasperini S, Del Toro M, Muschol N, et al. Intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A: A phase IIb randomized trial. Mol Genet Metab. 2019;126(2):121-30.
- Değerliyurt A, Yayıcı Köken Ö, Teker ND, Aktaş D. Significant neuropsychiatric symptoms: three mucopolysaccharidosis type IIIB cases, two of whom were siblings with a novel NAGLU gene mutation. Neurocase. 2021:1-6.
- Sampayo-Cordero M, Miguel-Huguet B, Pardo-Mateos A, Malfettone A, Perez-Garcia J, Llombart-Cussac A, et al. Agreement between results of meta-analyses from case reports and clinical studies, regarding efficacy and safety of idursulfase therapy in patients with mucopolysaccharidosis type II (MPS-II). A new tool for evidence-based medicine in rare diseases. Orphanet J Rare Dis. 2019;14(1):230.
- Abreu NJ, Selvaraj B, Truxal KV, Moore-Clingenpeel M, Zumberge NA, McNally KA, et al. Longitudinal MRI brain volume changes over one year in children with mucopolysaccharidosis types IIIA and IIIB. Molecular Genetics and Metabolism. 2021;133(2):193-200.
- Ergun P, Kagnıcı M, Ucar S, Coker M, Akcay Y, Sozmen E. Possible diagnostic markers for Mucopolysaccharidoses; Cathepsin-D, Galectin-3 and Chitotriosidase. IZMIR DR BEHCET UZ COCUK HASTANESI DERGISI. 2017;7(2).
- Escolar M, Bradshaw J, Byers VT, Giugliani R, Golightly L, Lourenço CM, et al. Development of a Clinical Algorithm for the Early Diagnosis of Mucopolysaccharidosis III. Journal of Inborn Errors of Metabolism and Screening. 2020;8.
- Ghosh A, Rust S, Langford-Smith K, Weisberg D, Canal M, Breen C, et al. High dose genistein in Sanfilippo syndrome: A randomised controlled trial. J Inherit Metab Dis. 2021;44(5):1248-62.
- Seker Yilmaz B, Davison J, Jones SA, Baruteau J. Novel therapies for mucopolysaccharidosis type III. Journal of Inherited Metabolic Disease. 2021;44(1):129-47.
- Yazici H, Canda E, Er E, Ucar S, Onay H, Ozkinay F, et al. Clinical, biochemical and molecular characteristics of fifteen patients with mucopolysaccharidosis type II in Western Turkey. JOURNAL OF PEDIATRIC RESEARCH. 2018;5(1).
- Wolfenden C, Wittkowski A, Jones SA, Rust S, Hare DJ. Autism spectrum disorder symptomatology in children with mucopolysaccharide disease type III. British Journal of Learning Disabilities. 2019;47(1):5-11.
- Hoffmann F, Hoffmann S, Kunzmann K, Ries M. Challenging behavior in mucopolysaccharidoses types I–III and day-to-day coping strategies: a cross sectional explorative study. Orphanet journal of rare diseases. 2020;15(1):1-14.
- Ucar SK, Ozbaran B, Demiral N, Yuncu Z, Erermis S, Coker M. Clinical overview of children with mucopolysaccharidosis type III A and effect of Risperidone treatment on children and their mothers psychological status. Brain and Development. 2010;32(2):156-61.
- Scarpa M, Lourenço CM, Amartino H. Epilepsy in mucopolysaccharidosis disorders. Molecular genetics and metabolism. 2017;122:55-61.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Çocuk Metabolizma Hastalıkları |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 8 Eylül 2025 |
| Gönderilme Tarihi | 30 Ağustos 2024 |
| Kabul Tarihi | 21 Nisan 2025 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 64 Sayı: 3 |
