Skip to main content
SpringerLink
Log in
Book cover

JIMD Reports, Volume 19 pp 85–93Cite as

Molecular Diagnosis of Hereditary Fructose Intolerance: Founder Mutation in a Community from India

  • Case Report
  • Chapter
  • First Online:

Part of the book series: JIMD Reports ((JIMD,volume 19))

Abstract

Hereditary fructose intolerance (HFI) is a difficult-to-confirm diagnosis, requiring either invasive liver biopsy-enzyme assay or potentially hazardous fructose challenge test or expensive molecular genetic analysis. Therefore, worldwide there has been a trend towards finding “common mutations” in distinct ethnic groups to simplify the process of diagnosis. The nonspecific presentation of the disease often leads to diagnostic confusion with other metabolic liver disorders such as glycogenoses, galactosemia, and tyrosinemia. This leads to much delay in diagnosis with consequent harm to the patient.

We report mutations in the ALDOB gene, from eleven Indian patients, seven of whom belong to the Agarwal community. Six patients from the Agarwal community and two non-Agarwal patients harbored one novel mutation, c.324+1G>A (five homozygous and one heterozygous), in the ALDOB gene. Haplotyping performed in families confirmed a founder effect. The community has been known to harbor founder mutations in other genes such as the MLC1, PANK2, and CAPN3 genes, thus providing another evidence for a founder effect in the community in case of HFI. This may pave the path for a simpler and quicker test at least for this community in India. In addition to the founder mutation, we report four other novel mutations, c.112+1delG, c.380-1G>A, c.677G>A, and c.689delA, and a previously reported mutation, c.1013C>T, in the cohort from India.

Competing interests: None declared

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Ananth N, Praveenkumar GS, Rao KA, Vasanthi, Kakkilaya S (2003) Two cases of hereditary fructose intolerance. Indian J Clin Biochem 18(2):87–92

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ankala A, Kohn JN, Dastur R, Gaitonde P, Khadilkar SV, Hegde MR (2013) Ancestral founder mutations in calpain-3 in the Indian Agarwal community: historical, clinical, and molecular perspective. Muscle Nerve 47(6):931–937

    Article  CAS  PubMed  Google Scholar 

  • Bahl S, Virdi K, Mittal U, Sachdeva MP, Kalla AK, Holmes SE, O’Hearn E, Margolis RL, Jain S, Srivastava AK, Mukerji M (2005) Evidence of a common founder for SCA12 in the Indian population. Ann Hum Genet 69:528–534

    Article  CAS  PubMed  Google Scholar 

  • Bharadia L, Shivpuri D (2012) Non responsive celiac disease due to coexisting hereditary fructose intolerance. Indian J Gastroenterol 31(2):83–84

    Article  PubMed  Google Scholar 

  • Blanco E, Parra G, Guigó R (2007) Using gene id to identify genes. Curr Protoc Bioinformatics. doi:10.1002/0471250953.bi0403s18

    PubMed  Google Scholar 

  • Brooks CC, Tolan DR (1993) Association of the widespread p.A149P hereditary fructose intolerance mutation with newly identified sequence polymorphisms in the Aldolase B gene. Am J Hum Genet 52:835–840

    PubMed Central  CAS  PubMed  Google Scholar 

  • Burge C, Karlin S (1997) Prediction of complete gene structures in human genomic DNA. J Mol Biol 268(1):78–94

    Article  CAS  PubMed  Google Scholar 

  • Chabbria R, Udani V, Das S, Shah R (2007) Founder mutation in the PANK gene of Agrawal children with neurodegeneration with brain iron accumulation (NBIA). Ann Indian Acad Neurol Suppl 2 10:33

    Google Scholar 

  • Coffee EM, Yerkes L, Ewen EP, Zee T, Tolan ER (2010) Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population. J Inherit Metab Dis 33(1):33–42

    Article  PubMed Central  PubMed  Google Scholar 

  • Esposito G, Imperato MR, Ieno L, Sorvillo R, Benigno V, Parenti G, Parini R, Vitagliano L, Zagari A, Salvatore F (2010) Hereditary fructose intolerance: functional study of two novel ALDOB natural variants and characterization of a partial gene deletion. Hum Mutat 31(12):1294–1303

    Article  CAS  PubMed  Google Scholar 

  • Gorospe JR, Singhal BS, Kainu T, Wu F, Stephan D, Trent J, Hoffman EP, Naidu S (2004) Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation. Neurology 62(6):878–882

    Article  CAS  PubMed  Google Scholar 

  • Lomsadze A, Ter-Hovhannisyan V, Chernoff YO, Borodovsky M (2005) Gene identification in novel eukaryotic genomes by self-training algorithm. Nucleic Acids Res 33(20):6494–6506

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Malay AD, Allen KN, Tolan DR (2005) Structure of the thermolabile mutant aldolase B, A149P: molecular basis of hereditary fructose intolerance. J Mol Biol 347(1):135–144

    Article  CAS  PubMed  Google Scholar 

  • Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic acid Res 16:1215

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sali A, Blundell TL (1993) Comparative protein modelling by satisfaction of spatial restraints. J Mol Biol 234(3):779–815

    Article  CAS  PubMed  Google Scholar 

  • Singhal BS (2005) Leukodystrophies – Indian scenario. Indian J Pediatr 72(4):315–318

    Article  CAS  PubMed  Google Scholar 

  • Stanke M, Steinkamp R, Waack S, Morgenstern B (2004) AUGUSTUS: a web server for gene finding in eukaryotes. Nucleic Acids Res 32(Web server issue):W309–W312

    Google Scholar 

  • Steinmann B, Gitzelmann R (1981) The diagnosis of hereditary fructose intolerance. Helv Paediatr Acta 36:297–316

    CAS  PubMed  Google Scholar 

  • Steinmann B, Santer R (2012) Disorders of fructose metabolism. In: Saudubray JM, van den Berghe G, Walter JH (eds) Inborn metabolic disorders – diagnosis and treatment, 5th edn. Springer, New York, pp 159–165

    Google Scholar 

Download references

Acknowledgements

We would like to acknowledge the contribution of Dr Rebecca Treacy and Dr J Drummond, East Anglican Medical Genetics Service Genetics Lab, Addenbrooke’s hospital, Cambridge, UK, for sequencing of the ALDOB gene in two patients. Deepak Sharma is thankful to his institute for the core grant for the bioinformatic study.

Author information

Authors and Affiliations

  1. Center of Medical Genetics, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India

    Sunita Bijarnia-Mahay, Sireesha Movva, Ratna D. Puri, Udhaya Kotecha, Renu Saxena & Ishwar C Verma

  2. Ganga Ram Institute for Post Graduate Medical Education and Research (GRIPMER), Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, India

    Sunita Bijarnia-Mahay, Ratna D. Puri, Udhaya Kotecha, Renu Saxena & Ishwar C Verma

  3. Genetics Division, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India

    Neerja Gupta & Madhulika Kabra

  4. Vaccine and Infectious Disease Research Centre, Translational Health Science and Technology Institute, Gurgaon, Haryana, India

    Deepak Sharma

  5. Department of Pediatric Gastroenterology and Hepatology, Medanta – The Medicity, Gurgaon, Haryana, India

    Neelam Mohan

Authors
  1. Sunita Bijarnia-Mahay
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sireesha Movva
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neerja Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Deepak Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ratna D. Puri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Udhaya Kotecha
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Renu Saxena
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Madhulika Kabra
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Neelam Mohan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ishwar C Verma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sunita Bijarnia-Mahay .

Editor information

Editors and Affiliations

  1. Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria

    Johannes Zschocke

  2. Division for Metabolic Diseases, University Children´s Hospital, Zürich, Switzerland

    Matthias Baumgartner

  3. Tulane University Medical School, New Orleans, Louisiana, USA

    Eva Morava

  4. Division of Child and Adolescent Neurolo, Mayo Clinic, Rochester, USA

    Marc Patterson

  5. Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, United Kingdom

    Shamima Rahman

  6. Centre for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

    Verena Peters

Additional information

Communicated by: Gajja Salomons

Appendices

Take-Home Message

First report of molecular mutations in HFI from India, founder mutation in the Agarwal community. Simplifying diagnosis for easily treatable yet life-threatening metabolic condition.

Conflict of Interest

All the authors (Sunita Bijarnia-Mahay, Sireesha Movva, Neerja Gupta, Deepak Sharma, Ratna D. Puri, Udhaya Kotecha, Renu Saxena, Madhulika Kabra, Neelam Mohan and Ishwar C Verma) declare that they have no conflict of interest.

This article does not contain any studies with human or animal subjects performed by any of the authors.

Details of the Contributions of Individual Authors

  • Sunita Bijarnia-Mahay

    1. 1.

      Conception and design

    2. 2.

      Clinical management of children with HFI

    3. 3.

      Analysis and interpretation of data

    4. 4.

      Drafting the article

  • Sireesha Movva

    1. 1.

      Analysis and interpretation of data, haplotype analysis

    2. 2.

      Drafting the article (molecular methodology)

  • Neerja Gupta

    1. 1.

      Conception and design

    2. 2.

      Clinical management of children with HFI

    3. 3.

      Drafting the article (provided patient information)

  • Deepak Sharma

    1. 1.

      Analysis and interpretation of data (computational analysis and bioinformatics)

    2. 2.

      Drafting the article (methodology and results of bioinformatics)

  • Ratna Dua Puri

    1. 1.

      Conception and design

    2. 2.

      Clinical management of children with HFI

    3. 3.

      Drafting the article (provided patient information)

  • Udhaya Kotecha

    1. 1.

      Conception and design

    2. 2.

      Clinical management of children with HFI

    3. 3.

      Drafting the article (provided patient information)

  • Renu Saxena

    1. 1.

      Analysis and interpretation of data, haplotype analysis

    2. 2.

      Revising it critically for important intellectual content)

  • Madhulika Kabra

    1. 1.

      Conception and design

    2. 2.

      Clinical management of children with HFI

  • Neelam Mohan

    1. 1.

      Conception and design

    2. 2.

      Clinical management of children with HFI

  • Ishwar C Verma

    1. 1.

      Clinical management of children with HFI

    2. 2.

      Revising it critically for important intellectual content)

Rights and permissions

Reprints and permissions

Copyright information

© 2014 SSIEM and Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Bijarnia-Mahay, S. et al. (2014). Molecular Diagnosis of Hereditary Fructose Intolerance: Founder Mutation in a Community from India. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 19. JIMD Reports, vol 19. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_374

Download citation

  • DOI: https://doi.org/10.1007/8904_2014_374

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-46189-1

  • Online ISBN: 978-3-662-46190-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation