Skip to main content

Advertisement

SpringerLink
Log in

An approach to recognising and identifying metabolic presentations in the paediatric Irish Traveller population

  • Review
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

The Irish Traveller population are an endogamous, traditionally nomadic, Irish population. Irish Travellers practice consanguinity in the majority of marriages, thus resulting in a higher rate of rare autosomal recessive conditions within the population due to homozygous variants. Herein, we outline the clinical phenotypes associated with metabolic conditions seen in this population presenting in the neonatal period, infancy and childhood. Although Irish Travellers are traditionally based in Ireland and the UK, there are populations also living in mainland Europe and the USA. While there is generally an understanding amongst Irish paediatricians of the recessive conditions seen with this population in Ireland, they may be less commonly encountered abroad. It is important to consider a non-genetic aetiology alongside any consideration for a metabolic disorder.

Conclusion: This paper acts as a comprehensive review of the metabolic conditions seen and provides a guide for the investigation of an Irish Traveller child with a suspected metabolic condition.

What is Known:

• The Irish Traveller population are an endogenous population.

• There are higher rates of inherited metabolic conditions in this population compared to the general population in Ireland.

What is New:

• This paper is a comprehensive review of all known inherited metabolic conditions encountered in the Irish Traveller population.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ACTH:

Adrenocorticotropic hormone

ASD:

Autism Spectrum Disorder

C:

Clan

COX:

Cytochrome C Oxidase

CSF:

Cerebrospinal fluid

DHPR:

Dihydropteridine reductase deficiency

EEG:

Electroencephalogram

F:

Founder

FA:

Friedreich ataxia

GA-1:

Glutaric Aciduria type 1

GAG:

Glycosaminoglycans

GSD:

Glycogen Storage Disease

HSCT:

Haematopoetic stem cell transplant

HCU:

Classical homocysteinuria

MCADD:

Medium-chain acyl-CoA dehydrogenase deficiency

MRI:

Magnetic Resonance Imaging

MSUD:

Maple Syrup Urine Disease

P:

Private

PKU:

Phenylketonuria

UK:

United Kingdom

References

  1. Lynch SA, Crushell E, Lambert DM, Byrne N, Gorman K, King MD, Green A, O’Sullivan S, Browne F, Hughes J, Knerr I, Monavari AA, Cotter M, McConnell VPM, Kerr B, Jones SA, Keenan C, Murphy N, Cody D, Ennis S, Turner J, Irvine AD, Casey J (2018) Catalogue of inherited disorders found among the Irish Traveller population. J Med Genet 55:233–239

    Article  CAS  Google Scholar 

  2. Murphy A, Halling C, Lynch S, Monavari A, Harty S, Crushell E, Treacy E (2008) A prospective study of referrals from the Irish Traveller community to the National Centre for Inherited Metabolic Disorders. Ulster Med J 77:65

    Google Scholar 

  3. AlAbdi L, Alrashseed S, Alsulaiman A, Helaby R, Imtiaz F, Alhamed M, Alkuraya FS (2021) Residual risk for additional recessive diseases in consanguineous couples. Genet Med Official J Am College Med Genet 23:2448–2454

    Article  CAS  Google Scholar 

  4. Health Service Executive (2022) Newborn Screening. HSE, Ireland. https://www.hse.ie/eng/health/child/newbornscreening/. Accessed Nov 2022

  5. Pugliese M, Tingley K, Chow A, Pallone N, Smith M, Chakraborty P, Geraghty MT et al (2021) Core outcome sets for medium-chain Acyl-CoA dehydrogenase deficiency and phenylketonuria. Pediatrics 148

  6. Schreuder AB, Rossi A, Grünert SC, Derks TGJ (1993) Glycogen storage disease type III. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A (eds) GeneReviews(®). University of Washington, Seattle, Seattle (WA)

  7. Rubio-Gozalbo ME, Haskovic M, Bosch AM, Burnyte B, Coelho AI, Cassiman D, Couce ML et al (2019) The natural history of classic galactosemia: lessons from the GalNet registry. Orphanet J Rare Dis 14:86

    Article  CAS  Google Scholar 

  8. Neville S, O’Sullivan S, Sweeney B, Lynch B, Hanrahan D, Knerr I, Lynch SA, Crushell E (2016) Friedreich ataxia in classical galactosaemia. JIMD Reports 26:1–5

    Article  Google Scholar 

  9. Boy N, Muhlhausen C, Maier EM, Heringer J, Assmann B, Burgard P, Dixon M, Fleissner S, Greenberg CR, Harting I, Hoffmann GF, Karall D, Koeller DM, Krawinkel MB, Okun JG, Opladen T, Posset R, Sahm K, Zschocke J, Kolker S (2017) Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type I: second revision. J Inherit Metab Dis 40:75–101

    Article  Google Scholar 

  10. Manoli I, Sloan JL, Venditti CP (1993) Isolated methylmalonic acidemia. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A (eds) GeneReviews(®). University of Washington, Seattle, Seattle (WA)

  11. Strauss KA, Puffenberger EG, Carson VJ (1993) Maple syrup urine disease. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A (eds) GeneReviews(®). University of Washington, Seattle, Seattle (WA)

  12. Grunert SC, Schlatter SM, Schmitt RN, Gemperle-Britschgi C, Mrazova L, Balci MC, Bischof F, Coker M, Das AM, Demirkol M, de Vries M, Gokcay G, Haberle J, Ucar SK, Lotz-Havla AS, Lucke T, Roland D, Rutsch F, Santer R, Schlune A, Staufner C, Schwab KO, Mitchell GA, Sass JO (2017) 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: clinical presentation and outcome in a series of 37 patients. Mol Genet Metab 121:206–215

    Article  Google Scholar 

  13. Quinonez SC, Thoene JG (1993) Dihydrolipoamide dehydrogenase deficiency. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A (eds) GeneReviews((R)). University of Washington, Seattle, Seattle (WA)

  14. Regier DS, Greene CL (1993) Phenylalanine hydroxylase deficiency. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A (eds). University of Washington, Seattle, Seattle (WA)

  15. Ponzone A, Spada M, Ferraris S, Dianzani I, de Sanctis L (2004) Dihydropteridine reductase deficiency in man: from biology to treatment. Med Res Rev 24:127–150

    Article  CAS  Google Scholar 

  16. van Kuilenburg AB, Meinsma R, Beke E, Assmann B, Ribes A, Lorente I, Busch R, Mayatepek E, Abeling NG, van Cruchten A, Stroomer AE, van Lenthe H, Zoetekouw L, Kulik W, Hoffmann GF, Voit T, Wevers RA, Rutsch F, van Gennip AH (2004) beta-Ureidopropionase deficiency: an inborn error of pyrimidine degradation associated with neurological abnormalities. Hum Mol Genet 13:2793–2801

    Article  Google Scholar 

  17. Invernizzi F, Legati A, Nasca A, Lamantea E (2021) Myopathic mitochondrial DNA depletion syndrome associated with biallelic variants in LIG3. 144:e74

  18. Stapleton M, Hoshina H, Sawamoto K, Kubaski F, Mason RW, Mackenzie WG, Theroux M, Kobayashi H, Yamaguchi S, Suzuki Y, Fukao T, Tadao O, Ida H, Tomatsu S (2019) Critical review of current MPS guidelines and management. Mol Genet Metab 126:238–245

    Article  CAS  Google Scholar 

  19. Murphy AM, Lambert D, Treacy EP, O’Meara A, Lynch SA (2009) Incidence and prevalence of mucopolysaccharidosis type 1 in the Irish republic. Arch Dis Child 94:52–54

    Article  CAS  Google Scholar 

  20. Wortmann SB, Zietkiewicz S, Kousi M, Szklarczyk R, Haack TB, Gersting SW, Muntau AC et al (2015) CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. Am J Hum Genet 96:245–257

    Article  CAS  Google Scholar 

  21. Murphy AM, Flanagan O, Dunne K, Lynch SA (2007) High prevalence of Cohen syndrome among Irish travellers. Clin Dysmorphol 16:257–259

    Article  Google Scholar 

  22. Iyer NS, Gimovsky AC, Ferreira CR, Critchlow E (2021) Lysosomal storage disorders as an etiology of nonimmune hydrops fetalis: a systematic review 100:493–503

    CAS  Google Scholar 

  23. Dogterom EJ, Wagenmakers M, Wilke M, Demirdas S, Muschol NM, Pohl S, Meijden JCV, Rizopoulos D, Ploeg ATV, Oussoren E (2021) Mucolipidosis type II and type III: a systematic review of 843 published cases. 23:2047–2056

  24. Mc Elliggott F, O’Sullivan S, Hughes J, Lambert D, Cooper A, Crushell E (2011) Incidence of I-cell disease (mucolipidosis type II) in the Irish Population. Ulster Med J 166–174

  25. Alston CL, Ceccatelli Berti C, Blakely EL, Oláhová M, He L, McMahon CJ, Olpin SE, Hargreaves IP, Nolli C, McFarland R, Goffrini P, O’Sullivan MJ, Taylor RW (2015) A recessive homozygous p.Asp92Gly SDHD mutation causes prenatal cardiomyopathy and a severe mitochondrial complex II deficiency. Hum Genet 134:869–879

    Article  CAS  Google Scholar 

  26. Felzen A, Verkade HJ (2021) The spectrum of progressive familial intrahepatic cholestasis diseases: update on pathophysiology and emerging treatments. Eur J Med Genet 64:104317

    Article  CAS  Google Scholar 

  27. Mitsubuchi H, Nakamura K, Matsumoto S, Endo F (2014) Biochemical and clinical features of hereditary hyperprolinemia. Pediatr Int Official J Japan Pediatr Soc 56:492–496

    Article  CAS  Google Scholar 

  28. Weiss KH (1993) Wilson Disease. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Mirzaa GM, Amemiya A (eds) GeneReviews(®). University of Washington, Seattle, Seattle (WA)

  29. Healy L, O’Shea M, McNulty J, King G, Twomey E, Treacy E, Crushell E, Hughes J, Knerr I, Monavari AA (2022) Glutaric aciduria type 1: diagnosis, clinical features and long-term outcome in a large cohort of 34 Irish patients. JIMD reports 63:379–387

    Article  Google Scholar 

  30. Baertling F, Rodenburg RJ, Schaper J, Smeitink JA, Koopman WJ, Mayatepek E, Morava E, Distelmaier F (2014) A guide to diagnosis and treatment of Leigh syndrome. J Neurol Neurosurg Psychiatry 85:257–265

    Article  Google Scholar 

  31. Casey JP, McGettigan P, Lynam-Lennon N, McDermott M, Regan R, Conroy J, Bourke B, O’Sullivan J, Crushell E, Lynch S, Ennis S (2012) Identification of a mutation in LARS as a novel cause of infantile hepatopathy. Mol Genet Metab 106:351–358

    Article  CAS  Google Scholar 

  32. Cohen BH, Chinnery PF, Copeland WC (1993) POLG-related disorders. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A (eds) GeneReviews((R)). University of Washington, Seattle., Seattle (WA)

  33. Lin S, Fasham J, Al-Hijawi F, Qutob N, Gunning A, Leslie JS (2021) Consolidating biallelic SDHD variants as a cause of mitochondrial complex II deficiency 29:1570–1576

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. National Centre for Inherited Metabolic Disorders, Children’s Health Ireland, Temple Street, Dublin 1, Ireland

    E. B. Forman, I. Knerr, A. Monavari, J. Hughes, R. Boruah & E. Crushell

  2. European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN), Dublin, Ireland

    E. B. Forman, I. Knerr, A. Monavari, J. Hughes, R. Boruah & E. Crushell

  3. Department of Clinical Genetics, Children’s Health Ireland, Crumlin, Dublin 12, Ireland

    S. A. Lynch & A. Green

  4. School of Medicine and Medical Science, University College Dublin, Dublin, Ireland

    S. A. Lynch, I. Knerr, A. Monavari, A. Green & E. Crushell

Authors
  1. E. B. Forman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. A. Lynch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. Knerr
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Monavari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. Hughes
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Boruah
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. Green
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E. Crushell
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the clinical and genetic information and reviewed the manuscript.

Corresponding author

Correspondence to E. B. Forman.

Ethics declarations

Ethics approval

No ethics approval was necessary for this manuscript.

Competing interests

The authors declare no competing interests.

Additional information

Communicated by Peter de Winter

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Several authors of this publication are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN)—Project ID No 739543.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Forman, E.B., Lynch, S.A., Knerr, I. et al. An approach to recognising and identifying metabolic presentations in the paediatric Irish Traveller population. Eur J Pediatr 182, 31–40 (2023). https://doi.org/10.1007/s00431-022-04697-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-022-04697-0

Keywords

Search

Navigation