Clinical & Genetic Patterns of Gaucher Disease in Kurdistan Region
Keywords:
Gaucher disease, Genetic mutation, Glucocerebrosidase enzyme
Abstract
https://doi.org/10.31386/dmj.2024.18.2.4
Background and objectives:
Gaucher disease is a rare autosomal recessive lysosomal storage disease and the most frequent form of the sphingolipidoses owing to lysosomal glucocerebrosidase enzyme activity insufficiency that is attributed to glucosylceramidase beta (GBA1) gene imperfection. As yet, close to 460 pathological variations as mutations have been perceived. This study worked towards assessment of phenotypic characteristic and genetic constitution of patients with Gaucher disease in Kurdistan region.
Patients and methods:
This cross-sectional study involved 23 patients; all were assessed for β- glucocerebrosidase enzyme level. Patients with reduced enzyme level were further evaluated to verify the diagnosis of Gaucher disease through molecular genetic analysis.
Results:
Hepatosplenomegaly, anaemia, pallor, and thrombocytopenia were reported in (95.7%) of cases. The mutation c. 1448T>C in homozygous status was ascertained in (34.8%) of Gaucher cases. The genotype c.1246G>A in homozygous status was determined in (30.8%) of cases with Kurdish descent. The difference in the genetic composition of the three ethnic groups was significant (P=0.062).
Conclusion:
The prime mutation in patients with Gaucher disease in Kurdistan Region was c. 1448T>C. The Gaucher disease type-1- was verified as prevailing phenotype of Gaucher disease.
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References
1.Giuffrida G, Markovic U, Condorelli A, Calafiore V, Nicolosi D, Calagna M et al. Glucosylsphingosine (Lys o-Gb1) as a reliable biomarker in Gaucher disease: a narrative review. Orphanet J Rare Dis. 2023 Feb 13;18(1):27.https://doi.org/10.1186/s13023-023-02623-7.
2. Gary SE, Ryan E, Steward AM, Sidransky E. Recent advances in the diagnosis and management of Gaucher disease. Expert Rev Endocrinol Metab. 2018 Mar;13(2):107-118.https://doi.org/10.1080/17446651.2018.1445524.
3.Puri RD, Kapoor S, Kishnani PS, Dalal A, Gupta N, Muranjan M et al. Gaucher Disease Task Force. Diagnosis and Management of Gaucher Disease in India - Consensus Guidelines of the Gaucher Disease Task Force of the Society for Indian Academy of Medical Genetics and the Indian Academy of Pediatrics. Indian Pediatr. 2018 Feb 15;55(2):143-153.https://www.indianpediatrics.net/feb2018/143.
4.Weinreb NJ, Goker-Alpan O, Kishnani PS, Longo N, Burrow TA, Bernat JA et al. The diagnosis and management of Gaucher disease in pediatric patients: Where do we go from here? Mol Genet Metab. 2022 May;136(1):4-21.https://doi.org/10.1016/j.ymgme.2022.03.001.
5.Alasmar D. Gaucher disease in Syrian children: common mutations identification, and clinical futures. Ann Saudi Med. 2015 Mar-Apr;35(2):127-32.https://doi.org/10.5144/0256-4947.2015.127.
6.Nalysnyk L, Rotella P, Simeone JC, Hamed A, Weinreb N. Gaucher disease epidemiology and natural history: a comprehensive review of the literature. Hematology. 2017 Mar;22(2):65-73. https://doi.org/10.1080/10245332.2016.1240391.
7.Wang M, Li F, Zhang J, Lu C, Kong W. Global Epidemiology of Gaucher Disease: an Updated Systematic Review and Meta-analysis. J Pediatr Hematol Oncol. 2023 May 1;45(4):181-188.https://doi.org/10.1097/mph.0000000000002506.
8.Kinghorn KJ, Grönke S, Castillo-Quan JI, Woodling NS, Li L, Sirka E et al. A Drosophila Model of Neuronopathic Gaucher Disease Demonstrates Lysosomal-Autophagic Defects and Altered mTOR Signaling and Is Functionally Rescued by Rapamycin. J Neurosci. 2016 Nov 16;36(46):11654-11670.https://doi.org/10.1523/jneurosci.4527-15.2016.
9.Schiffmann R, Sevigny J, Rolfs A, Davies EH, Goker-Alpan O, Abdelwahab M et al. The definition of neuronopathic Gaucher disease. J Inherit Metab Dis. 2020 Sep;43(5):1056-1059.https://doi.org/10.1002/jimd.12235.
10.Dardis A, Michelakakis H, Rozenfeld P, Fumic K, Wagner J, Pavan E et al. International Working Group of Gaucher Disease (IWGGD). Patient centered guidelines for the laboratory diagnosis of Gaucher disease type 1. Orphanet J Rare Dis. 2022 Dec 21;17(1):442.https://doi.org/10.1186/s13023-022-02573-6.
11.Stirnemann J, Belmatoug N, Camou F, Serratrice C, Froissart R, Caillaud C, Levade T, Astudillo L, Serratrice J, Brassier A, Rose C, Billette de Villemeur T, Berger MG. A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. Int J Mol Sci. 2017 Feb 17;18(2):441.https://doi.org/10.3390/ijms18020441.
12.Tseng SY, Niu DM, Chu TH, Yeh YC, Huang MH, Yang TF et al. Very rare condition of multiple Gaucheroma: A case report and review of the literature. Mol Genet Metab Rep. 2019 May 9;20:100473.https://doi.org/10.1016/j.ymgmr.2019.100473.
13.Ramaswami U, Mengel E, Berrah A, AlSayed M, Broomfield A, Donald A et al. Throwing a spotlight on under-recognized manifestations of Gaucher disease: Pulmonary involvement, lymphadenopathy and Gaucheroma. Mol Genet Metab. 2021 Aug;133(4):335-344.https://doi.org/10.1016/j.ymgme.2021.06.009.
14.Alcalay RN, Dinur T, Quinn T, Sakanaka K, Levy O, Waters C et al. Comparison of Parkinson risk in Ashkenazi Jewish patients with Gaucher disease and GBA heterozygotes. JAMA Neurol. 2014 Jun;71(6):752-7.https://doi.org/10.1001/jamaneurol.2014.313.
15.Chida R, Shimura M, Ishida Y, Suganami Y, Yamanaka G. Perinatal lethal Gaucher disease: A case report and review of literature. Brain Dev. 2023 Feb;45(2):134-139.https://doi.org/10.1016/j.braindev.2022.09.006.
16.Carr PC, Casamiquela KM, Jacks SK. Gaucher Disease Type 2 Presenting with Collodion Membrane and Blueberry Muffin Lesions. Pediatr Dermatol. 2016 Jan-Feb;33(1):e20-2.https://doi.org/10.1111/pde.12733.
17. Roshan Lal T, Sidransky E. The Spectrum of Neurological Manifestations Associated with Gaucher Disease. Diseases. 2017 Mar 2;5(1):10.https://doi.org/10.3390/diseases5010010.
18. Weiss K, Gonzalez A, Lopez G, Pedoeim L, Groden C, Sidransky E. The clinical management of Type 2 Gaucher disease. Mol Genet Metab. 2015 Feb;114(2):110-122.https://doi.org/10.1016/j.ymgme.2014.11.008.
19.Schwartz IVD, Göker-Alpan Ö, Kishnani PS, Zimran A, Renault L, Panahloo Z et al.GOS Study group. Characteristics of 26 patients with type 3 Gaucher disease: A descriptive analysis from the Gaucher Outcome Survey. Mol Genet Metab Rep. 2017 Dec 27;14:73-79.https://doi.org/10.1016/j.ymgmr.2017.10.011.
20.Pastores GM, Hughes DA. Gaucher Disease. 2000 Jul 27 [updated 2023 Mar 9]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023.https://www.ncbi.nlm.nih.gov/books/NBK1269/.
21.Fateen E, Abdallah ZY. Twenty- five years of biochemical diagnosis of Gaucher disease: the Egyptian experience. Heliyon. 2019 Nov 1;5(10):e02574.https://doi.org/10.1016/j.heliyon.2019.e02574.
22.Sam R, Ryan E, Daykin E, Sidransky E. Current and emerging pharmacotherapy for Gaucher disease in pediatric populations. Expert Opin Pharmacother. 2021 Aug;22(11):1489-1503.https://doi.org/10.1080/14656566.2021.1902989.
23.Shemesh E, Deroma L, Bembi B, Deegan P, Hollak C, Weinreb NJ et al. Enzyme replacement and substrate reduction therapy for Gaucher disease. Cochrane Database Syst Rev. 2015 Mar 27;2015(3):CD010324.https://doi.org/10.1002/14651858.cd010324.pub2.
24.Hannah-Shmouni F, Amato D. Three cases of multi-generational Gaucher disease and colon cancer from an Ashkenazi Jewish family: A lesson for cascade screening. Mol Genet Metab Rep. 2019 Jan 4;18:19-21.https://doi.org/10.1016/j.ymgmr.2019.01.001.
25.Feng Y, Huang Y, Tang C, Hu H, Zhao X, Sheng H et al. Clinical and molecular characteristics of patients with Gaucher disease in Southern China. Blood Cells Mol Dis. 2018 Feb;68:30-34.https://doi.org/10.1016/j.bcmd.2016.10.026.
26. Wolf P, Alcalay RN, Liong C, Cullen E, Pauciulo MW, Nichols WC et al. Tandem mass spectrometry assay of β-glucocerebrosidase activity in dried blood spots eliminates false positives detected in fluorescence assay. Mol Genet Metab. 2018 Feb;123(2):135-139.https://doi.org/10.1016/j.ymgme.2017.10.011.
27.Thejeal RF, Kadhum AJ. Gaucher disease in Iraqi children (Clinical, diagnostic & therapeutic aspects). Pak J Med Sci. 2016 Mar-Apr;32(2):319-23.https://doi.org/10.12669/pjms.322.9316.
28. D'Amore S, Page K, Donald A, Taiyari K, Tom B, Deegan P, Tan CY, Poole K, Jones SA, Mehta A, Hughes D, Sharma R, Lachmann RH, Chakrapani A, Geberhiwot T, Santra S, Banka S, Cox TM; MRC GAUCHERITE Consortium. In-depth phenotyping for clinical stratification of Gaucher disease. Orphanet J Rare Dis. 2021 Oct 14;16(1):431.https://doi.org/10.1186/s13023-021-02034-6.
29.Sheth J, Bhavsar R, Mistri M, Pancholi D, Bavdekar A, Dalal A et al. Gaucher disease: single gene molecular characterization of one-hundred Indian patients reveals novel variants and the most prevalent mutation. BMC Med Genet. 2019 Feb 14;20(1):31.https://doi.org/10.1186/s12881-019-0759-1.
30. Ben Halim N, Hsouna S, Lasram K, Rejeb I, Walha A, Talmoudi F et al. Differential impact of consanguineous marriages on autosomal recessive diseases in Tunisia. Am J Hum Biol. 2016 Mar-Apr;28(2):171-80.https://doi.org/10.1002/ajhb.22764.
31. Gumus E, Karhan AN, Hizarcioglu-Gulsen H, Demir H, Ozen H, Saltik Temizel IN et al. Clinical-genetic characteristics and treatment outcomes of Turkish children with Gaucher disease type 1 and type 3: A sixteen year single-center experience. Eur J Med Genet. 2021 Nov;64(11):104339.https://doi.org/10.1016/j.ejmg.2021.104339.
32. Saleem TH, Hassan MH, El-Abd Ahmed A, Sayed AA, Mohamed NA, Elsayh KI et al. Clinical and genetic assessment of pediatric patients with Gaucher’s disease in Upper Egypt. Egyptian Journal of Medical Human Genetics. 2017;18(3):249-55.https://www.ajol.info/index.php/ejhg/article/view/159513/149066.
33. Mohanraj S, Prasad HK. Delayed Puberty. Indian J Pediatr. 2023 Jun;90(6):590-597.https://doi.org/10.1007/s12098-023-04577-x.
34. Giraldo P, Pérez-López J, Núñez R, de la Puebla RF, Luño E, Saura-Grau S et al. Patients with type 1 Gaucher disease in Spain: A cross-sectional evaluation of health status. Blood Cells Mol Dis. 2016 Jan;56(1):23-30.https://doi.org/10.1016/j.bcmd.2015.10.001.
35. Fateen EM, Fathy HM, Maaty DM, Kamel NM, Aleem AK. Mutational analysis of a cohort of Egyptian patients with Gaucher disease. Middle East Journal of Medical Genetics. 2017 Jul 1;6(2):61-9.http://dx.doi.org/10.1097/01.MXE.0000520527.54080.ab.
36. Alaei M, Jafari N, Rohani F, Ahmadabadi F, Azadi R. Are There Neurological Symptoms in Type 1 of Gaucher Disease? Iran J Child Neurol. 2018 Spring;12(2):99-106.http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5904744/.
37. Hannah-Shmouni F, Amato D. Three cases of multi-generational Gaucher disease and colon cancer from an Ashkenazi Jewish family: A lesson for cascade screening. Mol Genet Metab Rep. 2019 Jan 4;18:19-21.https://doi.org/10.1016/j.ymgmr.2019.01.001.
1.Giuffrida G, Markovic U, Condorelli A, Calafiore V, Nicolosi D, Calagna M et al. Glucosylsphingosine (Lys o-Gb1) as a reliable biomarker in Gaucher disease: a narrative review. Orphanet J Rare Dis. 2023 Feb 13;18(1):27.https://doi.org/10.1186/s13023-023-02623-7.
2. Gary SE, Ryan E, Steward AM, Sidransky E. Recent advances in the diagnosis and management of Gaucher disease. Expert Rev Endocrinol Metab. 2018 Mar;13(2):107-118.https://doi.org/10.1080/17446651.2018.1445524.
3.Puri RD, Kapoor S, Kishnani PS, Dalal A, Gupta N, Muranjan M et al. Gaucher Disease Task Force. Diagnosis and Management of Gaucher Disease in India - Consensus Guidelines of the Gaucher Disease Task Force of the Society for Indian Academy of Medical Genetics and the Indian Academy of Pediatrics. Indian Pediatr. 2018 Feb 15;55(2):143-153.https://www.indianpediatrics.net/feb2018/143.
4.Weinreb NJ, Goker-Alpan O, Kishnani PS, Longo N, Burrow TA, Bernat JA et al. The diagnosis and management of Gaucher disease in pediatric patients: Where do we go from here? Mol Genet Metab. 2022 May;136(1):4-21.https://doi.org/10.1016/j.ymgme.2022.03.001.
5.Alasmar D. Gaucher disease in Syrian children: common mutations identification, and clinical futures. Ann Saudi Med. 2015 Mar-Apr;35(2):127-32.https://doi.org/10.5144/0256-4947.2015.127.
6.Nalysnyk L, Rotella P, Simeone JC, Hamed A, Weinreb N. Gaucher disease epidemiology and natural history: a comprehensive review of the literature. Hematology. 2017 Mar;22(2):65-73. https://doi.org/10.1080/10245332.2016.1240391.
7.Wang M, Li F, Zhang J, Lu C, Kong W. Global Epidemiology of Gaucher Disease: an Updated Systematic Review and Meta-analysis. J Pediatr Hematol Oncol. 2023 May 1;45(4):181-188.https://doi.org/10.1097/mph.0000000000002506.
8.Kinghorn KJ, Grönke S, Castillo-Quan JI, Woodling NS, Li L, Sirka E et al. A Drosophila Model of Neuronopathic Gaucher Disease Demonstrates Lysosomal-Autophagic Defects and Altered mTOR Signaling and Is Functionally Rescued by Rapamycin. J Neurosci. 2016 Nov 16;36(46):11654-11670.https://doi.org/10.1523/jneurosci.4527-15.2016.
9.Schiffmann R, Sevigny J, Rolfs A, Davies EH, Goker-Alpan O, Abdelwahab M et al. The definition of neuronopathic Gaucher disease. J Inherit Metab Dis. 2020 Sep;43(5):1056-1059.https://doi.org/10.1002/jimd.12235.
10.Dardis A, Michelakakis H, Rozenfeld P, Fumic K, Wagner J, Pavan E et al. International Working Group of Gaucher Disease (IWGGD). Patient centered guidelines for the laboratory diagnosis of Gaucher disease type 1. Orphanet J Rare Dis. 2022 Dec 21;17(1):442.https://doi.org/10.1186/s13023-022-02573-6.
11.Stirnemann J, Belmatoug N, Camou F, Serratrice C, Froissart R, Caillaud C, Levade T, Astudillo L, Serratrice J, Brassier A, Rose C, Billette de Villemeur T, Berger MG. A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. Int J Mol Sci. 2017 Feb 17;18(2):441.https://doi.org/10.3390/ijms18020441.
12.Tseng SY, Niu DM, Chu TH, Yeh YC, Huang MH, Yang TF et al. Very rare condition of multiple Gaucheroma: A case report and review of the literature. Mol Genet Metab Rep. 2019 May 9;20:100473.https://doi.org/10.1016/j.ymgmr.2019.100473.
13.Ramaswami U, Mengel E, Berrah A, AlSayed M, Broomfield A, Donald A et al. Throwing a spotlight on under-recognized manifestations of Gaucher disease: Pulmonary involvement, lymphadenopathy and Gaucheroma. Mol Genet Metab. 2021 Aug;133(4):335-344.https://doi.org/10.1016/j.ymgme.2021.06.009.
14.Alcalay RN, Dinur T, Quinn T, Sakanaka K, Levy O, Waters C et al. Comparison of Parkinson risk in Ashkenazi Jewish patients with Gaucher disease and GBA heterozygotes. JAMA Neurol. 2014 Jun;71(6):752-7.https://doi.org/10.1001/jamaneurol.2014.313.
15.Chida R, Shimura M, Ishida Y, Suganami Y, Yamanaka G. Perinatal lethal Gaucher disease: A case report and review of literature. Brain Dev. 2023 Feb;45(2):134-139.https://doi.org/10.1016/j.braindev.2022.09.006.
16.Carr PC, Casamiquela KM, Jacks SK. Gaucher Disease Type 2 Presenting with Collodion Membrane and Blueberry Muffin Lesions. Pediatr Dermatol. 2016 Jan-Feb;33(1):e20-2.https://doi.org/10.1111/pde.12733.
17. Roshan Lal T, Sidransky E. The Spectrum of Neurological Manifestations Associated with Gaucher Disease. Diseases. 2017 Mar 2;5(1):10.https://doi.org/10.3390/diseases5010010.
18. Weiss K, Gonzalez A, Lopez G, Pedoeim L, Groden C, Sidransky E. The clinical management of Type 2 Gaucher disease. Mol Genet Metab. 2015 Feb;114(2):110-122.https://doi.org/10.1016/j.ymgme.2014.11.008.
19.Schwartz IVD, Göker-Alpan Ö, Kishnani PS, Zimran A, Renault L, Panahloo Z et al.GOS Study group. Characteristics of 26 patients with type 3 Gaucher disease: A descriptive analysis from the Gaucher Outcome Survey. Mol Genet Metab Rep. 2017 Dec 27;14:73-79.https://doi.org/10.1016/j.ymgmr.2017.10.011.
20.Pastores GM, Hughes DA. Gaucher Disease. 2000 Jul 27 [updated 2023 Mar 9]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023.https://www.ncbi.nlm.nih.gov/books/NBK1269/.
21.Fateen E, Abdallah ZY. Twenty- five years of biochemical diagnosis of Gaucher disease: the Egyptian experience. Heliyon. 2019 Nov 1;5(10):e02574.https://doi.org/10.1016/j.heliyon.2019.e02574.
22.Sam R, Ryan E, Daykin E, Sidransky E. Current and emerging pharmacotherapy for Gaucher disease in pediatric populations. Expert Opin Pharmacother. 2021 Aug;22(11):1489-1503.https://doi.org/10.1080/14656566.2021.1902989.
23.Shemesh E, Deroma L, Bembi B, Deegan P, Hollak C, Weinreb NJ et al. Enzyme replacement and substrate reduction therapy for Gaucher disease. Cochrane Database Syst Rev. 2015 Mar 27;2015(3):CD010324.https://doi.org/10.1002/14651858.cd010324.pub2.
24.Hannah-Shmouni F, Amato D. Three cases of multi-generational Gaucher disease and colon cancer from an Ashkenazi Jewish family: A lesson for cascade screening. Mol Genet Metab Rep. 2019 Jan 4;18:19-21.https://doi.org/10.1016/j.ymgmr.2019.01.001.
25.Feng Y, Huang Y, Tang C, Hu H, Zhao X, Sheng H et al. Clinical and molecular characteristics of patients with Gaucher disease in Southern China. Blood Cells Mol Dis. 2018 Feb;68:30-34.https://doi.org/10.1016/j.bcmd.2016.10.026.
26. Wolf P, Alcalay RN, Liong C, Cullen E, Pauciulo MW, Nichols WC et al. Tandem mass spectrometry assay of β-glucocerebrosidase activity in dried blood spots eliminates false positives detected in fluorescence assay. Mol Genet Metab. 2018 Feb;123(2):135-139.https://doi.org/10.1016/j.ymgme.2017.10.011.
27.Thejeal RF, Kadhum AJ. Gaucher disease in Iraqi children (Clinical, diagnostic & therapeutic aspects). Pak J Med Sci. 2016 Mar-Apr;32(2):319-23.https://doi.org/10.12669/pjms.322.9316.
28. D'Amore S, Page K, Donald A, Taiyari K, Tom B, Deegan P, Tan CY, Poole K, Jones SA, Mehta A, Hughes D, Sharma R, Lachmann RH, Chakrapani A, Geberhiwot T, Santra S, Banka S, Cox TM; MRC GAUCHERITE Consortium. In-depth phenotyping for clinical stratification of Gaucher disease. Orphanet J Rare Dis. 2021 Oct 14;16(1):431.https://doi.org/10.1186/s13023-021-02034-6.
29.Sheth J, Bhavsar R, Mistri M, Pancholi D, Bavdekar A, Dalal A et al. Gaucher disease: single gene molecular characterization of one-hundred Indian patients reveals novel variants and the most prevalent mutation. BMC Med Genet. 2019 Feb 14;20(1):31.https://doi.org/10.1186/s12881-019-0759-1.
30. Ben Halim N, Hsouna S, Lasram K, Rejeb I, Walha A, Talmoudi F et al. Differential impact of consanguineous marriages on autosomal recessive diseases in Tunisia. Am J Hum Biol. 2016 Mar-Apr;28(2):171-80.https://doi.org/10.1002/ajhb.22764.
31. Gumus E, Karhan AN, Hizarcioglu-Gulsen H, Demir H, Ozen H, Saltik Temizel IN et al. Clinical-genetic characteristics and treatment outcomes of Turkish children with Gaucher disease type 1 and type 3: A sixteen year single-center experience. Eur J Med Genet. 2021 Nov;64(11):104339.https://doi.org/10.1016/j.ejmg.2021.104339.
32. Saleem TH, Hassan MH, El-Abd Ahmed A, Sayed AA, Mohamed NA, Elsayh KI et al. Clinical and genetic assessment of pediatric patients with Gaucher’s disease in Upper Egypt. Egyptian Journal of Medical Human Genetics. 2017;18(3):249-55.https://www.ajol.info/index.php/ejhg/article/view/159513/149066.
33. Mohanraj S, Prasad HK. Delayed Puberty. Indian J Pediatr. 2023 Jun;90(6):590-597.https://doi.org/10.1007/s12098-023-04577-x.
34. Giraldo P, Pérez-López J, Núñez R, de la Puebla RF, Luño E, Saura-Grau S et al. Patients with type 1 Gaucher disease in Spain: A cross-sectional evaluation of health status. Blood Cells Mol Dis. 2016 Jan;56(1):23-30.https://doi.org/10.1016/j.bcmd.2015.10.001.
35. Fateen EM, Fathy HM, Maaty DM, Kamel NM, Aleem AK. Mutational analysis of a cohort of Egyptian patients with Gaucher disease. Middle East Journal of Medical Genetics. 2017 Jul 1;6(2):61-9.http://dx.doi.org/10.1097/01.MXE.0000520527.54080.ab.
36. Alaei M, Jafari N, Rohani F, Ahmadabadi F, Azadi R. Are There Neurological Symptoms in Type 1 of Gaucher Disease? Iran J Child Neurol. 2018 Spring;12(2):99-106.http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5904744/.
37. Hannah-Shmouni F, Amato D. Three cases of multi-generational Gaucher disease and colon cancer from an Ashkenazi Jewish family: A lesson for cascade screening. Mol Genet Metab Rep. 2019 Jan 4;18:19-21.https://doi.org/10.1016/j.ymgmr.2019.01.001.
2. Gary SE, Ryan E, Steward AM, Sidransky E. Recent advances in the diagnosis and management of Gaucher disease. Expert Rev Endocrinol Metab. 2018 Mar;13(2):107-118.https://doi.org/10.1080/17446651.2018.1445524.
3.Puri RD, Kapoor S, Kishnani PS, Dalal A, Gupta N, Muranjan M et al. Gaucher Disease Task Force. Diagnosis and Management of Gaucher Disease in India - Consensus Guidelines of the Gaucher Disease Task Force of the Society for Indian Academy of Medical Genetics and the Indian Academy of Pediatrics. Indian Pediatr. 2018 Feb 15;55(2):143-153.https://www.indianpediatrics.net/feb2018/143.
4.Weinreb NJ, Goker-Alpan O, Kishnani PS, Longo N, Burrow TA, Bernat JA et al. The diagnosis and management of Gaucher disease in pediatric patients: Where do we go from here? Mol Genet Metab. 2022 May;136(1):4-21.https://doi.org/10.1016/j.ymgme.2022.03.001.
5.Alasmar D. Gaucher disease in Syrian children: common mutations identification, and clinical futures. Ann Saudi Med. 2015 Mar-Apr;35(2):127-32.https://doi.org/10.5144/0256-4947.2015.127.
6.Nalysnyk L, Rotella P, Simeone JC, Hamed A, Weinreb N. Gaucher disease epidemiology and natural history: a comprehensive review of the literature. Hematology. 2017 Mar;22(2):65-73. https://doi.org/10.1080/10245332.2016.1240391.
7.Wang M, Li F, Zhang J, Lu C, Kong W. Global Epidemiology of Gaucher Disease: an Updated Systematic Review and Meta-analysis. J Pediatr Hematol Oncol. 2023 May 1;45(4):181-188.https://doi.org/10.1097/mph.0000000000002506.
8.Kinghorn KJ, Grönke S, Castillo-Quan JI, Woodling NS, Li L, Sirka E et al. A Drosophila Model of Neuronopathic Gaucher Disease Demonstrates Lysosomal-Autophagic Defects and Altered mTOR Signaling and Is Functionally Rescued by Rapamycin. J Neurosci. 2016 Nov 16;36(46):11654-11670.https://doi.org/10.1523/jneurosci.4527-15.2016.
9.Schiffmann R, Sevigny J, Rolfs A, Davies EH, Goker-Alpan O, Abdelwahab M et al. The definition of neuronopathic Gaucher disease. J Inherit Metab Dis. 2020 Sep;43(5):1056-1059.https://doi.org/10.1002/jimd.12235.
10.Dardis A, Michelakakis H, Rozenfeld P, Fumic K, Wagner J, Pavan E et al. International Working Group of Gaucher Disease (IWGGD). Patient centered guidelines for the laboratory diagnosis of Gaucher disease type 1. Orphanet J Rare Dis. 2022 Dec 21;17(1):442.https://doi.org/10.1186/s13023-022-02573-6.
11.Stirnemann J, Belmatoug N, Camou F, Serratrice C, Froissart R, Caillaud C, Levade T, Astudillo L, Serratrice J, Brassier A, Rose C, Billette de Villemeur T, Berger MG. A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. Int J Mol Sci. 2017 Feb 17;18(2):441.https://doi.org/10.3390/ijms18020441.
12.Tseng SY, Niu DM, Chu TH, Yeh YC, Huang MH, Yang TF et al. Very rare condition of multiple Gaucheroma: A case report and review of the literature. Mol Genet Metab Rep. 2019 May 9;20:100473.https://doi.org/10.1016/j.ymgmr.2019.100473.
13.Ramaswami U, Mengel E, Berrah A, AlSayed M, Broomfield A, Donald A et al. Throwing a spotlight on under-recognized manifestations of Gaucher disease: Pulmonary involvement, lymphadenopathy and Gaucheroma. Mol Genet Metab. 2021 Aug;133(4):335-344.https://doi.org/10.1016/j.ymgme.2021.06.009.
14.Alcalay RN, Dinur T, Quinn T, Sakanaka K, Levy O, Waters C et al. Comparison of Parkinson risk in Ashkenazi Jewish patients with Gaucher disease and GBA heterozygotes. JAMA Neurol. 2014 Jun;71(6):752-7.https://doi.org/10.1001/jamaneurol.2014.313.
15.Chida R, Shimura M, Ishida Y, Suganami Y, Yamanaka G. Perinatal lethal Gaucher disease: A case report and review of literature. Brain Dev. 2023 Feb;45(2):134-139.https://doi.org/10.1016/j.braindev.2022.09.006.
16.Carr PC, Casamiquela KM, Jacks SK. Gaucher Disease Type 2 Presenting with Collodion Membrane and Blueberry Muffin Lesions. Pediatr Dermatol. 2016 Jan-Feb;33(1):e20-2.https://doi.org/10.1111/pde.12733.
17. Roshan Lal T, Sidransky E. The Spectrum of Neurological Manifestations Associated with Gaucher Disease. Diseases. 2017 Mar 2;5(1):10.https://doi.org/10.3390/diseases5010010.
18. Weiss K, Gonzalez A, Lopez G, Pedoeim L, Groden C, Sidransky E. The clinical management of Type 2 Gaucher disease. Mol Genet Metab. 2015 Feb;114(2):110-122.https://doi.org/10.1016/j.ymgme.2014.11.008.
19.Schwartz IVD, Göker-Alpan Ö, Kishnani PS, Zimran A, Renault L, Panahloo Z et al.GOS Study group. Characteristics of 26 patients with type 3 Gaucher disease: A descriptive analysis from the Gaucher Outcome Survey. Mol Genet Metab Rep. 2017 Dec 27;14:73-79.https://doi.org/10.1016/j.ymgmr.2017.10.011.
20.Pastores GM, Hughes DA. Gaucher Disease. 2000 Jul 27 [updated 2023 Mar 9]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023.https://www.ncbi.nlm.nih.gov/books/NBK1269/.
21.Fateen E, Abdallah ZY. Twenty- five years of biochemical diagnosis of Gaucher disease: the Egyptian experience. Heliyon. 2019 Nov 1;5(10):e02574.https://doi.org/10.1016/j.heliyon.2019.e02574.
22.Sam R, Ryan E, Daykin E, Sidransky E. Current and emerging pharmacotherapy for Gaucher disease in pediatric populations. Expert Opin Pharmacother. 2021 Aug;22(11):1489-1503.https://doi.org/10.1080/14656566.2021.1902989.
23.Shemesh E, Deroma L, Bembi B, Deegan P, Hollak C, Weinreb NJ et al. Enzyme replacement and substrate reduction therapy for Gaucher disease. Cochrane Database Syst Rev. 2015 Mar 27;2015(3):CD010324.https://doi.org/10.1002/14651858.cd010324.pub2.
24.Hannah-Shmouni F, Amato D. Three cases of multi-generational Gaucher disease and colon cancer from an Ashkenazi Jewish family: A lesson for cascade screening. Mol Genet Metab Rep. 2019 Jan 4;18:19-21.https://doi.org/10.1016/j.ymgmr.2019.01.001.
25.Feng Y, Huang Y, Tang C, Hu H, Zhao X, Sheng H et al. Clinical and molecular characteristics of patients with Gaucher disease in Southern China. Blood Cells Mol Dis. 2018 Feb;68:30-34.https://doi.org/10.1016/j.bcmd.2016.10.026.
26. Wolf P, Alcalay RN, Liong C, Cullen E, Pauciulo MW, Nichols WC et al. Tandem mass spectrometry assay of β-glucocerebrosidase activity in dried blood spots eliminates false positives detected in fluorescence assay. Mol Genet Metab. 2018 Feb;123(2):135-139.https://doi.org/10.1016/j.ymgme.2017.10.011.
27.Thejeal RF, Kadhum AJ. Gaucher disease in Iraqi children (Clinical, diagnostic & therapeutic aspects). Pak J Med Sci. 2016 Mar-Apr;32(2):319-23.https://doi.org/10.12669/pjms.322.9316.
28. D'Amore S, Page K, Donald A, Taiyari K, Tom B, Deegan P, Tan CY, Poole K, Jones SA, Mehta A, Hughes D, Sharma R, Lachmann RH, Chakrapani A, Geberhiwot T, Santra S, Banka S, Cox TM; MRC GAUCHERITE Consortium. In-depth phenotyping for clinical stratification of Gaucher disease. Orphanet J Rare Dis. 2021 Oct 14;16(1):431.https://doi.org/10.1186/s13023-021-02034-6.
29.Sheth J, Bhavsar R, Mistri M, Pancholi D, Bavdekar A, Dalal A et al. Gaucher disease: single gene molecular characterization of one-hundred Indian patients reveals novel variants and the most prevalent mutation. BMC Med Genet. 2019 Feb 14;20(1):31.https://doi.org/10.1186/s12881-019-0759-1.
30. Ben Halim N, Hsouna S, Lasram K, Rejeb I, Walha A, Talmoudi F et al. Differential impact of consanguineous marriages on autosomal recessive diseases in Tunisia. Am J Hum Biol. 2016 Mar-Apr;28(2):171-80.https://doi.org/10.1002/ajhb.22764.
31. Gumus E, Karhan AN, Hizarcioglu-Gulsen H, Demir H, Ozen H, Saltik Temizel IN et al. Clinical-genetic characteristics and treatment outcomes of Turkish children with Gaucher disease type 1 and type 3: A sixteen year single-center experience. Eur J Med Genet. 2021 Nov;64(11):104339.https://doi.org/10.1016/j.ejmg.2021.104339.
32. Saleem TH, Hassan MH, El-Abd Ahmed A, Sayed AA, Mohamed NA, Elsayh KI et al. Clinical and genetic assessment of pediatric patients with Gaucher’s disease in Upper Egypt. Egyptian Journal of Medical Human Genetics. 2017;18(3):249-55.https://www.ajol.info/index.php/ejhg/article/view/159513/149066.
33. Mohanraj S, Prasad HK. Delayed Puberty. Indian J Pediatr. 2023 Jun;90(6):590-597.https://doi.org/10.1007/s12098-023-04577-x.
34. Giraldo P, Pérez-López J, Núñez R, de la Puebla RF, Luño E, Saura-Grau S et al. Patients with type 1 Gaucher disease in Spain: A cross-sectional evaluation of health status. Blood Cells Mol Dis. 2016 Jan;56(1):23-30.https://doi.org/10.1016/j.bcmd.2015.10.001.
35. Fateen EM, Fathy HM, Maaty DM, Kamel NM, Aleem AK. Mutational analysis of a cohort of Egyptian patients with Gaucher disease. Middle East Journal of Medical Genetics. 2017 Jul 1;6(2):61-9.http://dx.doi.org/10.1097/01.MXE.0000520527.54080.ab.
36. Alaei M, Jafari N, Rohani F, Ahmadabadi F, Azadi R. Are There Neurological Symptoms in Type 1 of Gaucher Disease? Iran J Child Neurol. 2018 Spring;12(2):99-106.http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5904744/.
37. Hannah-Shmouni F, Amato D. Three cases of multi-generational Gaucher disease and colon cancer from an Ashkenazi Jewish family: A lesson for cascade screening. Mol Genet Metab Rep. 2019 Jan 4;18:19-21.https://doi.org/10.1016/j.ymgmr.2019.01.001.
1.Giuffrida G, Markovic U, Condorelli A, Calafiore V, Nicolosi D, Calagna M et al. Glucosylsphingosine (Lys o-Gb1) as a reliable biomarker in Gaucher disease: a narrative review. Orphanet J Rare Dis. 2023 Feb 13;18(1):27.https://doi.org/10.1186/s13023-023-02623-7.
2. Gary SE, Ryan E, Steward AM, Sidransky E. Recent advances in the diagnosis and management of Gaucher disease. Expert Rev Endocrinol Metab. 2018 Mar;13(2):107-118.https://doi.org/10.1080/17446651.2018.1445524.
3.Puri RD, Kapoor S, Kishnani PS, Dalal A, Gupta N, Muranjan M et al. Gaucher Disease Task Force. Diagnosis and Management of Gaucher Disease in India - Consensus Guidelines of the Gaucher Disease Task Force of the Society for Indian Academy of Medical Genetics and the Indian Academy of Pediatrics. Indian Pediatr. 2018 Feb 15;55(2):143-153.https://www.indianpediatrics.net/feb2018/143.
4.Weinreb NJ, Goker-Alpan O, Kishnani PS, Longo N, Burrow TA, Bernat JA et al. The diagnosis and management of Gaucher disease in pediatric patients: Where do we go from here? Mol Genet Metab. 2022 May;136(1):4-21.https://doi.org/10.1016/j.ymgme.2022.03.001.
5.Alasmar D. Gaucher disease in Syrian children: common mutations identification, and clinical futures. Ann Saudi Med. 2015 Mar-Apr;35(2):127-32.https://doi.org/10.5144/0256-4947.2015.127.
6.Nalysnyk L, Rotella P, Simeone JC, Hamed A, Weinreb N. Gaucher disease epidemiology and natural history: a comprehensive review of the literature. Hematology. 2017 Mar;22(2):65-73. https://doi.org/10.1080/10245332.2016.1240391.
7.Wang M, Li F, Zhang J, Lu C, Kong W. Global Epidemiology of Gaucher Disease: an Updated Systematic Review and Meta-analysis. J Pediatr Hematol Oncol. 2023 May 1;45(4):181-188.https://doi.org/10.1097/mph.0000000000002506.
8.Kinghorn KJ, Grönke S, Castillo-Quan JI, Woodling NS, Li L, Sirka E et al. A Drosophila Model of Neuronopathic Gaucher Disease Demonstrates Lysosomal-Autophagic Defects and Altered mTOR Signaling and Is Functionally Rescued by Rapamycin. J Neurosci. 2016 Nov 16;36(46):11654-11670.https://doi.org/10.1523/jneurosci.4527-15.2016.
9.Schiffmann R, Sevigny J, Rolfs A, Davies EH, Goker-Alpan O, Abdelwahab M et al. The definition of neuronopathic Gaucher disease. J Inherit Metab Dis. 2020 Sep;43(5):1056-1059.https://doi.org/10.1002/jimd.12235.
10.Dardis A, Michelakakis H, Rozenfeld P, Fumic K, Wagner J, Pavan E et al. International Working Group of Gaucher Disease (IWGGD). Patient centered guidelines for the laboratory diagnosis of Gaucher disease type 1. Orphanet J Rare Dis. 2022 Dec 21;17(1):442.https://doi.org/10.1186/s13023-022-02573-6.
11.Stirnemann J, Belmatoug N, Camou F, Serratrice C, Froissart R, Caillaud C, Levade T, Astudillo L, Serratrice J, Brassier A, Rose C, Billette de Villemeur T, Berger MG. A Review of Gaucher Disease Pathophysiology, Clinical Presentation and Treatments. Int J Mol Sci. 2017 Feb 17;18(2):441.https://doi.org/10.3390/ijms18020441.
12.Tseng SY, Niu DM, Chu TH, Yeh YC, Huang MH, Yang TF et al. Very rare condition of multiple Gaucheroma: A case report and review of the literature. Mol Genet Metab Rep. 2019 May 9;20:100473.https://doi.org/10.1016/j.ymgmr.2019.100473.
13.Ramaswami U, Mengel E, Berrah A, AlSayed M, Broomfield A, Donald A et al. Throwing a spotlight on under-recognized manifestations of Gaucher disease: Pulmonary involvement, lymphadenopathy and Gaucheroma. Mol Genet Metab. 2021 Aug;133(4):335-344.https://doi.org/10.1016/j.ymgme.2021.06.009.
14.Alcalay RN, Dinur T, Quinn T, Sakanaka K, Levy O, Waters C et al. Comparison of Parkinson risk in Ashkenazi Jewish patients with Gaucher disease and GBA heterozygotes. JAMA Neurol. 2014 Jun;71(6):752-7.https://doi.org/10.1001/jamaneurol.2014.313.
15.Chida R, Shimura M, Ishida Y, Suganami Y, Yamanaka G. Perinatal lethal Gaucher disease: A case report and review of literature. Brain Dev. 2023 Feb;45(2):134-139.https://doi.org/10.1016/j.braindev.2022.09.006.
16.Carr PC, Casamiquela KM, Jacks SK. Gaucher Disease Type 2 Presenting with Collodion Membrane and Blueberry Muffin Lesions. Pediatr Dermatol. 2016 Jan-Feb;33(1):e20-2.https://doi.org/10.1111/pde.12733.
17. Roshan Lal T, Sidransky E. The Spectrum of Neurological Manifestations Associated with Gaucher Disease. Diseases. 2017 Mar 2;5(1):10.https://doi.org/10.3390/diseases5010010.
18. Weiss K, Gonzalez A, Lopez G, Pedoeim L, Groden C, Sidransky E. The clinical management of Type 2 Gaucher disease. Mol Genet Metab. 2015 Feb;114(2):110-122.https://doi.org/10.1016/j.ymgme.2014.11.008.
19.Schwartz IVD, Göker-Alpan Ö, Kishnani PS, Zimran A, Renault L, Panahloo Z et al.GOS Study group. Characteristics of 26 patients with type 3 Gaucher disease: A descriptive analysis from the Gaucher Outcome Survey. Mol Genet Metab Rep. 2017 Dec 27;14:73-79.https://doi.org/10.1016/j.ymgmr.2017.10.011.
20.Pastores GM, Hughes DA. Gaucher Disease. 2000 Jul 27 [updated 2023 Mar 9]. In: Adam MP, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023.https://www.ncbi.nlm.nih.gov/books/NBK1269/.
21.Fateen E, Abdallah ZY. Twenty- five years of biochemical diagnosis of Gaucher disease: the Egyptian experience. Heliyon. 2019 Nov 1;5(10):e02574.https://doi.org/10.1016/j.heliyon.2019.e02574.
22.Sam R, Ryan E, Daykin E, Sidransky E. Current and emerging pharmacotherapy for Gaucher disease in pediatric populations. Expert Opin Pharmacother. 2021 Aug;22(11):1489-1503.https://doi.org/10.1080/14656566.2021.1902989.
23.Shemesh E, Deroma L, Bembi B, Deegan P, Hollak C, Weinreb NJ et al. Enzyme replacement and substrate reduction therapy for Gaucher disease. Cochrane Database Syst Rev. 2015 Mar 27;2015(3):CD010324.https://doi.org/10.1002/14651858.cd010324.pub2.
24.Hannah-Shmouni F, Amato D. Three cases of multi-generational Gaucher disease and colon cancer from an Ashkenazi Jewish family: A lesson for cascade screening. Mol Genet Metab Rep. 2019 Jan 4;18:19-21.https://doi.org/10.1016/j.ymgmr.2019.01.001.
25.Feng Y, Huang Y, Tang C, Hu H, Zhao X, Sheng H et al. Clinical and molecular characteristics of patients with Gaucher disease in Southern China. Blood Cells Mol Dis. 2018 Feb;68:30-34.https://doi.org/10.1016/j.bcmd.2016.10.026.
26. Wolf P, Alcalay RN, Liong C, Cullen E, Pauciulo MW, Nichols WC et al. Tandem mass spectrometry assay of β-glucocerebrosidase activity in dried blood spots eliminates false positives detected in fluorescence assay. Mol Genet Metab. 2018 Feb;123(2):135-139.https://doi.org/10.1016/j.ymgme.2017.10.011.
27.Thejeal RF, Kadhum AJ. Gaucher disease in Iraqi children (Clinical, diagnostic & therapeutic aspects). Pak J Med Sci. 2016 Mar-Apr;32(2):319-23.https://doi.org/10.12669/pjms.322.9316.
28. D'Amore S, Page K, Donald A, Taiyari K, Tom B, Deegan P, Tan CY, Poole K, Jones SA, Mehta A, Hughes D, Sharma R, Lachmann RH, Chakrapani A, Geberhiwot T, Santra S, Banka S, Cox TM; MRC GAUCHERITE Consortium. In-depth phenotyping for clinical stratification of Gaucher disease. Orphanet J Rare Dis. 2021 Oct 14;16(1):431.https://doi.org/10.1186/s13023-021-02034-6.
29.Sheth J, Bhavsar R, Mistri M, Pancholi D, Bavdekar A, Dalal A et al. Gaucher disease: single gene molecular characterization of one-hundred Indian patients reveals novel variants and the most prevalent mutation. BMC Med Genet. 2019 Feb 14;20(1):31.https://doi.org/10.1186/s12881-019-0759-1.
30. Ben Halim N, Hsouna S, Lasram K, Rejeb I, Walha A, Talmoudi F et al. Differential impact of consanguineous marriages on autosomal recessive diseases in Tunisia. Am J Hum Biol. 2016 Mar-Apr;28(2):171-80.https://doi.org/10.1002/ajhb.22764.
31. Gumus E, Karhan AN, Hizarcioglu-Gulsen H, Demir H, Ozen H, Saltik Temizel IN et al. Clinical-genetic characteristics and treatment outcomes of Turkish children with Gaucher disease type 1 and type 3: A sixteen year single-center experience. Eur J Med Genet. 2021 Nov;64(11):104339.https://doi.org/10.1016/j.ejmg.2021.104339.
32. Saleem TH, Hassan MH, El-Abd Ahmed A, Sayed AA, Mohamed NA, Elsayh KI et al. Clinical and genetic assessment of pediatric patients with Gaucher’s disease in Upper Egypt. Egyptian Journal of Medical Human Genetics. 2017;18(3):249-55.https://www.ajol.info/index.php/ejhg/article/view/159513/149066.
33. Mohanraj S, Prasad HK. Delayed Puberty. Indian J Pediatr. 2023 Jun;90(6):590-597.https://doi.org/10.1007/s12098-023-04577-x.
34. Giraldo P, Pérez-López J, Núñez R, de la Puebla RF, Luño E, Saura-Grau S et al. Patients with type 1 Gaucher disease in Spain: A cross-sectional evaluation of health status. Blood Cells Mol Dis. 2016 Jan;56(1):23-30.https://doi.org/10.1016/j.bcmd.2015.10.001.
35. Fateen EM, Fathy HM, Maaty DM, Kamel NM, Aleem AK. Mutational analysis of a cohort of Egyptian patients with Gaucher disease. Middle East Journal of Medical Genetics. 2017 Jul 1;6(2):61-9.http://dx.doi.org/10.1097/01.MXE.0000520527.54080.ab.
36. Alaei M, Jafari N, Rohani F, Ahmadabadi F, Azadi R. Are There Neurological Symptoms in Type 1 of Gaucher Disease? Iran J Child Neurol. 2018 Spring;12(2):99-106.http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5904744/.
37. Hannah-Shmouni F, Amato D. Three cases of multi-generational Gaucher disease and colon cancer from an Ashkenazi Jewish family: A lesson for cascade screening. Mol Genet Metab Rep. 2019 Jan 4;18:19-21.https://doi.org/10.1016/j.ymgmr.2019.01.001.
Published
2025-01-13
How to Cite
1.
Mohammed L. Clinical & Genetic Patterns of Gaucher Disease in Kurdistan Region. Duhok Medical Journal [Internet]. 13Jan.2025 [cited 4Jun.2026];18(2):34-. Available from: https://dmj.uod.ac/index.php/dmj/article/view/269
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