Volume 42, Issue 2 pp. 295-302

ORIGINAL ARTICLE

Quantitative natural history characterization in a cohort of 142 published cases of patients with galactosialidosis—A cross-sectional study

Tomáš Sláma,

Tomáš Sláma

Department of Pediatrics, University Children's Hospital Bern, University of Bern, Bern, Switzerland

University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland

Search for more papers by this author

Sven F. Garbade,

Sven F. Garbade

Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

Search for more papers by this author

Stefan Kölker,

Stefan Kölker

Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

Search for more papers by this author

Georg F. Hoffmann,

Georg F. Hoffmann

Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

Search for more papers by this author

Markus Ries,

Corresponding Author

Markus Ries

[email protected]

orcid.org/0000-0002-5054-5741

Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

Correspondence

Markus Ries, Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld 430, D-69120 Heidelberg, Germany.

Email: [email protected]

Search for more papers by this author

Tomáš Sláma,

Tomáš Sláma

Department of Pediatrics, University Children's Hospital Bern, University of Bern, Bern, Switzerland

University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, Bern, Switzerland

Search for more papers by this author

Sven F. Garbade,

Sven F. Garbade

Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

Search for more papers by this author

Stefan Kölker,

Stefan Kölker

Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

Search for more papers by this author

Georg F. Hoffmann,

Georg F. Hoffmann

Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

Search for more papers by this author

Markus Ries,

Corresponding Author

Markus Ries

[email protected]

orcid.org/0000-0002-5054-5741

Division of Pediatric Neurology and Metabolic Medicine, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

Correspondence

Email: [email protected]

Search for more papers by this author

First published: 27 December 2018

https://doi.org/10.1002/jimd.12010

Citations: 23

Share a link

Email
Wechat
Bluesky

Abstract

Galactosialidosis (GS; OMIM #256540) is a rare multisystemic inborn glycoprotein storage disease caused by biallelic mutations in the cathepsin A gene resulting in combined deficiency of the lysosomal enzymes β-galactosidase and α-neuraminidase. The precise understanding of the natural course of the disease is limited. Development of enzyme replacement therapy is at the preclinical stage. The purpose of this research project was to quantitatively characterize the natural history of the condition. Quantitative analysis of all published cases in the literature with sufficient data (N = 142 patients) was carried out. Main outcome variables were survival, diagnostic delay, description of symptoms, biomarker-phenotype associations, and radiological findings. STROBE criteria were respected. Median survival age of the cohort was 48 years. Median age of onset was 4.25 years with interquartile range (IQR) 1 to 16 years. Median age at diagnosis was 19 (IQR: 8.92-29) years, with median diagnostic delay of 8 (IQR: 4-12) years. Patients with residual β-galactosidase activity of more than 8.6% (leukocytes) survived significantly longer than patients with lower enzyme activities.

CONFLICTS OF INTEREST

M.R. received consultancy fees or research grants from Alexion, GSK, Oxyrane and Shire outside of this work. T.S., S.F.G., S.K. and G.F.H. declare that they have no conflicts of interest.

Supporting Information

Filename

Description

jimd12010-sup-0001-SupInfo.docxWord 2007 document , 924 KB

Appendix S1.

Figure S1. Study flow diagram: Identification of clinical case descriptions and case series of patients with galactosialidosis (GS). The reports analyzed were published latest up to February 2016.

Figure S2. Geographical distribution of galactosialidosis (GS) case reports.

Figure S3. Estimated survival distribution for galactosialidosis (GS) patients with a residual β-Gal activity above 8,64% (N = 39, red line) and below or equal to 8,64% of normal controls (N = 24, blue line). Enzymatic activity was measured in leucocytes.

Table S1. Reported subtype designation of patients with galactosialidosis (GS) as stated in studied case reports and our subtype designation.

Table S2. Demography of published patients with galactosialidosis (GS)

Table S3. Ethnicity of reported patients. Terminology as stated in original case reports.

Table S4. Causes of death in patients with galactosialidosis (GS). Total cases of death N = 34. Cause of death is known in 47% of deceased patients.

Table S5. Reported initial signs and symptoms (by subtype and overall, in descending order of overall frequency)

Table S6. Radiological findings: X-ray

Table S7. Radiological findings: magnetic resonance imaging (MRI)

Table S8. Radiological findings: computed tomography (CT)

Table S9. Radiological findings: Ultrasound

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

REFERENCES

1Goldberg MF, Cotlier E, Fichenscher LG, Kenyon K, Enat R, Borowsky SA. Macular cherry-red spot, corneal clouding, and beta-galactosidase deficiency. Clinical, biochemical, and electron microscopic study of a new autosomal recessive storage disease. Arch Intern Med. 1971; 128(3): 387-398.
10.1001/archinte.1971.00310210063005
CAS PubMed Google Scholar
2Darin N, Kyllerman M, Hård A-L, Nordborg C, Månsson J-E. Juvenile galactosialidosis with attacks of neuropathic pain and absence of sialyloligosacchariduria. Eur J Paediatr Neurol. 2009; 13(6): 553-555. https://doi.org/10.1016/j.ejpn.2008.11.003.
10.1016/j.ejpn.2008.11.003
PubMed Web of Science® Google Scholar
3Halal F, Chitayat D, Parikh H, et al. Ring chromosome 20 and possible assignment of the structural gene encoding human carboxypeptidase-L to the distal segment of the long arm of chromosome 20. Am J Med Genet. 1992; 43(3): 576-579. https://doi.org/10.1002/ajmg.1320430314.
10.1002/ajmg.1320430314
CAS PubMed Web of Science® Google Scholar
4Wenger DA, Tarby TJ, Wharton C. Macular cherry-red spots and myoclonus with dementia: coexistent neuraminidase and beta-galactosidase deficiencies. Biochem Biophys Res Commun. 1978; 82(2): 589-595.
10.1016/0006-291X(78)90915-4
CAS PubMed Web of Science® Google Scholar
5Zhou XY, van der Spoel A, Rottier R, et al. Molecular and biochemical analysis of protective protein/cathepsin a mutations: correlation with clinical severity in galactosialidosis. Hum Mol Genet. 1996; 5(12): 1977-1987.
10.1093/hmg/5.12.1977
CAS PubMed Web of Science® Google Scholar
6d'Azzo A, Hoogeveen A, Reuser AJ, Robinson D, Galjaard H. Molecular defect in combined beta-galactosidase and neuraminidase deficiency in man. Proc Natl Acad Sci USA. 1982; 79(15): 4535-4539.
10.1073/pnas.79.15.4535
PubMed Web of Science® Google Scholar
7Okamura-Oho Y, Zhang S, Callahan JW. The biochemistry and clinical features of galactosialidosis. Biochim Biophys Acta. 1994; 1225(3): 244-254.
10.1016/0925-4439(94)90002-7
CAS PubMed Web of Science® Google Scholar
8d'Azzo A, Andria G, Bonten E, Annunziata I. Galactosialidosis. In: D Valle, AL Baudet, B Vogelstein, et al., eds. The Online Metabolic and Molecular Bases of Inherited Disease. New York City: McGraw-Hill; 2013.
Google Scholar
9Prada CE, Gonzaga-Jauregui C, Tannenbaum R, et al. Clinical utility of whole-exome sequencing in rare diseases: Galactosialidosis. Eur J Med Genet. 2014; 57(7): 339-344. https://doi.org/10.1016/j.ejmg.2014.04.005.
10.1016/j.ejmg.2014.04.005
PubMed Web of Science® Google Scholar
10Strisciuglio P, Sly WS, Dodson WE, McAlister WH, Martin TC. Combined deficiency of beta-galactosidase and neuraminidase: natural history of the disease in the first 18 years of an American patient with late infantile onset form. Am J Med Genet. 1990; 37(4): 573-577. https://doi.org/10.1002/ajmg.1320370431.
10.1002/ajmg.1320370431
CAS PubMed Web of Science® Google Scholar
11Suzuki Y, Sakuraba H, Yamanaka T, et al. Galactosialidosis: a comparative study of clinical and biochemical data on 22 patients. In: M Arima, Y Suzuki, H Yabuuchi, eds. The Developing Brain and Its Disorders XX. Tokyo, Japan: University of Tokyo Press; 1984: 161-175.
Google Scholar
12Hothorn T, Hornik K, Zeileis A. Unbiased recursive partitioning: a conditional inference framework. J Comput Graph Stat. 2006; 15(3): 651-674. https://doi.org/10.1198/106186006X133933.
10.1198/106186006X133933
Web of Science® Google Scholar
13Kahle D, Wickham H. ggmap: spatial visualization with ggplot2. R J. 2013; 5(1): 144-161.
10.32614/RJ-2013-014
Web of Science® Google Scholar
14Mechler K, Mountford WK, Hoffmann GF, Ries M. Ultra-orphan diseases: a quantitative analysis of the natural history of molybdenum cofactor deficiency. Genet Med. 2015; 17(12): 965-970. https://doi.org/10.1038/gim.2015.12.
10.1038/gim.2015.12
CAS PubMed Web of Science® Google Scholar
15Zielonka M, Garbade SF, Kölker S, Hoffmann GF, Ries M. Quantitative clinical characteristics of 53 patients with MPS VII: a cross-sectional analysis. Genet Med. 2017a; 19(9): 983-988. https://doi.org/10.1038/gim.2017.10.
10.1038/gim.2017.10
CAS PubMed Web of Science® Google Scholar
16Zielonka M, Garbade SF, Kölker S, Hoffmann GF, Ries M. A cross-sectional quantitative analysis of the natural history of Farber disease: an ultra-orphan condition with rheumatologic and neurological cardinal disease features. Genet Med. 2017b; 20: 524-530. https://doi.org/10.1038/gim.2017.133.
10.1038/gim.2017.133
PubMed Web of Science® Google Scholar
17Koppaka V, Cadaoas J, Cullen S, et al. Recombinant Human Protective Protein/Cathepsin A: An Update on the Development of an Enzyme Replacement Therapy for Galactosialidosis. Poster presented at the: 12th Annual WORLD Symposium™; March 1, 2016; San Diego, CA. http://www.ultragenyx.com/file.cfm/22/docs/2016%20WORLD%20Poster%20_UX004.pdf. Accessed June 24, 2018.
Google Scholar
18Ries M, Schiffmann R. Fabry disease: angiokeratoma, biomarker, and the effect of enzyme replacement therapy on kidney function. Arch Dermatol. 2005; 141(7): 904-905; author reply 905-906. https://doi.org/10.1001/archderm.141.7.904-b.
10.1001/archderm.141.7.904-b
PubMed Google Scholar

Citing Literature

Volume42, Issue2

March 2019

Pages 295-302

This article also appears in:

Inherited Metabolic Disorders in Adults

Quantitative natural history characterization in a cohort of 142 published cases of patients with galactosialidosis—A cross-sectional study

Abstract

CONFLICTS OF INTEREST

Supporting Information

REFERENCES

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Quantitative natural history characterization in a cohort of 142 published cases of patients with galactosialidosis—A cross-sectional study

Abstract

CONFLICTS OF INTEREST

Supporting Information

REFERENCES

Citing Literature

References

Related

Information