Inborn Errors of Intermediary Metabolism in Critically Ill Infants at a Tertiary Care Children Hospital
Abstract
Background:-
Inborn errors of intermediary metabolism are complex genetic disorders with clinical heterogeneity. Infants with such disorders present with diverse clinical manifestations ranging from acute life threatening to chronic late onset forms with single or multiorgan involvement
Objective:-To study the clinical characteristics, spectrum and outcome in critically ill infants, suspected of IEM at a tertiary care children hospital.
Methods: -.
We screened 136 critically ill infants who fulfilled the inclusion criteria, over a period of two years with ethical clearance from Ethical Clearance Committee of GMC (Ref No. 121/ETH/GMC/ICMR). The clinical characteristics of study group were recorded and investigations which included ABG, lactate, ammonia levels and TMS & GCMS (Tandem Mass Spectrometry & Gas Chromatography Mass Spectrometry) were done. Those patients who were confirmed by TMS & GCMS as having IEM were evaluated for their outcome.
Results:-
136 patients who fulfilled the inclusion criteria, 32 (23.5%) had IEM. Of these 32 patients 12 had organic acidemias ,8 had primary lactic acidosis ,6 had amino acid disorders with 50% as Maple syrup urine disease , 4 had urea cycle disorders ( citrullinemia type- I) ,Acyl Co-A dehydrogenase deficiency 1 & 1 had biotinidase deficiency .These patients mostly presented with fast breathing, vomiting, seizures ,refusal of feeds and encephalopathy followed by rapid circulatory & respiratory decompensation .This study found stastically significant association between IEM and, parental consanguinity, history of sib death and sudden clinical deterioration. Mortality rate in diagnosed IEM infants was 75%.
Conclusion:-
Suspicion of IEM in critically ill infants is required when there is history of parental consanguinity, history of previous sib death or rapid clinical deterioration .We recommend a large study to determine the prevalence of different types of IEM.
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References
2. Burton BK .Inborn errors of metabolism in infancy :a guide to diagnosis .Pediatrics .1998;102(6):E69
3. Plass AM, van ElCG, pieters T, cornel MC. Neonatal screening for treatable &untreatable disorders prospective parents ‘opinions
pediatrics.2010;125(1):e106.doi:10.1542/peds.2009-0269.
4 Chakrapani A, Cleary MA, Wraith JE. Detection of inborn errors of metabolism in the newborn. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2001 May 1;84(3):F205-10., 5th ed.,
2009.
5. Vela-Amieva M,Ibarra-Gonzalez I,Fernandez-Lainez C,etal. Causes of delay in referrals of patients with phenylketonuria to a specialised reference centre in Mexio.J Med Screen .2011:18(3)115-120.
6. Saudubray, J.M. et al. Clinical approach to inherited metabolic disorders in neonates: an overview.Seminars in Neonatology , Volume 7 , Issue 1 , 3 - 15.
7. Snustad DP, Simmons MJ. Principles of genetics, binder ready version. John Wiley & Sons; 2009.
8. Gupta, A, Anthropology Today: Trends, Scopes and Applications. New Delhi: Kamla-Raj Enterprises;2007,415-423.
9. Pandey AS. Metabolic disease in Nepal: A perspective. Kathmandu Univ Med J. 2010;8(31):333-40.
10. Martins AM. Inborn errors of metabolism: a clinical overview. Sao Paulo Medical Journal. 1999 Nov;117(6):251-65.
11. Cross, Simon S, J C. E. Underwood, and J C. E. Underwood. Underwood's Pathology: A Clinical Approach. Edinburgh: Churchill Livingstone, 2013. Internet resource.
12. Rao AN, Kavitha J, Koch M, Kumar VS. Inborn errors of metabolism: Review and data from a tertiary care center. Indian Journal of Clinical Biochemistry. 2009 Jul 1;24(3):215-22.
13. Beaudet AL. Genetics, biochemistry and molecular basis of variant human phenotypes. The metabolic and molecular bases of inherited disease. 1995:53-118.
14. Kim CA, Albano LM, Bertola DR. Genética na prática pediátrica. São Paulo: Manole; 2010.
15.R JAILKHANI, VS PATIL et al Selective Screening For Inborn Errors Of Metabolism in Children: Single Center Experience From Karnataka 2008;52-958.
16. Shela Choudhary, Masood Khan, Hani Akhbar Rao, Anil Jahan, Ejaz Ahmad Khan. Etiology and outcome of inborn errors of metabolism. JPMA 2013; 63: 11-12.
17. Huma Arshad Cheema, Hassan Suleman Malik, et al Spectrum of Inherited Metabolic Disorders in Pakistani Children Presenting at a Tertiary Care Centre. Journal of the College of Physicians and Surgeons Pakistan 2016; Vol. 26 (6): 498-502.
18. Satwani H, Raza J, Hanai J, Nomachi S. Prevalence of selected disorders of inborn errors of metabolism in suspected cases at a Tertiary Care Hospital in Karachi. JPMA. 2009;59(815).
19. Abbasi F, Setoodeh A, Sayarifard F, Rostami P, Rabbani A. Inborn Errors of Metabolism-Clinical Findings and Laboratory Tests at the Children's Medical Center, Tehran, Iran. Iranian Journal of Pediatrics. 2016 Dec 1;26(6).
20. Fateen E, Gouda A, Boehles H, Sewell A. Inborn errors of metabolism revealed by organic acid profile analysis in high risk Egyptian patients: Six years experience. Egyptian Journal of Medical Human Genetics. 2009;10(2).
21.Joshi SN, Venugopalan P. Clinical characteristics of neonates with inborn errors of metabolism detected by Tandem MS analysis in Oman. Brain and Development. 2007 Oct 1;29(9):543-6.
22. Huang X, Yang L, Tong F, Yang R, Zhao Z. Screening for inborn errors of metabolism in high-risk children: a 3-year pilot study in Zhejiang Province, China. BMC pediatrics. 2012 Dec;12(1):18.
23. Choudhry S, Khan M, Rao HA, Jalan A, Khan EA. Etiology and outcome of inborn errors of metabolism. J Pak Med Assoc. 2013 Sep 1;63(9):1112-6.
24. Gul SS, Majeed AI, Talpur AF. Inborn errors of metabolism in newborns: An experience of tertiary care hospital in Islamabad. Ann Pak Inst Med Sci. 2017;13(2):213-6.
25.Ibarra GI, Fernándecxvc z LC, Reyes GD, Belmont ML, Guillén LS, Monroy SS. Inborn errors of intermediary metabolism in critically ill mexican newborns. J Inborn Errors Metabol Screening.2014:1-7.
26. Tan I, Gajra B, Lim MS. Study of inherited metabolic disorders in Singapore-13 years experience. ANNALS-ACADEMY OF MEDICINE SINGAPORE. 2006 Nov 1;35(11):804.
27. AlObaidy H. Patterns of inborn errors of metabolism: A 12 year single-center hospital-based study in Libya. Qatar medical journal. 2014 Apr 1:18.
28.Al-Thihli K, Al-Murshedi F, Al-Hashmi N, Al-Mamari W, Islam MM, Al-Yahyaee SA. Consanguinity, endogamy and inborn errors of metabolism in Oman: a cross-sectional study. Human heredity. 2014;77(1-4):183-8.
29.Jovet P,Touati G, Lesage F, etal. Impact of inborn errors of metabolism on admission & mortality in pediatric intensive care unit . Eur J pediatr 2007;166(5):461-465.
30.Nagaraja D, Mamatha SN, De T, Christopher R. Screening for inborn errors of metabolism using automated electrospray tandem mass spectrometry: study in symptomatic Indian population. Clin Biochem. 2010;43:581–588
31.Rabbah M. Shawky, 20. Heba Salah Abd-Elkhalek, 20. Samah Elyamani Elakhdar. Selective screening in neonates suspected to have inborn errors of metabolism. 20. Egyptian Journal of Medical Human Genetics 2015; 20. Volume 16, Issue 2: Pages 165–171.
32.Millington D, Koeberl D. Metabolic screening in the newborn. GGH. 2003;19(3):33-8.
33. Ibrra Gonzalez Isabel et al. Inborn Errors of Intermediary Metabolism in Critically Ill Mexican
Newborns. Journal of Inborn Errors of Metabolism and Screening January 2014; Vol.22326409814529649.
34Vilarinho L, Rocha H, Sousa C, Marcão A, Fonseca H, Bogas M, Osório RV. Four years ofexpanded newborn screening in Portugal with tandem mass spectrometry. J Inherit MetabDis. 2010.
35. Yoon HR, Lee KR, Kang S, Lee DH, Yoo HW, et al. Screening of newborn and symptomatic groupof children for inborn metabolic disorders using tandem mass spectrometry in South Korea: a three-year report. Clin Chim Acta. 2005;354:167–180.
36.Gu XF, Han LS, Gao XL, Yan YL, Ye J, Qiu WJ. A pilot study of selective screening for high risk children with inborn errors of metabolism using tandem mass spectrometry in China. Zhonghua ErKe ZaZhi. 2004;42:401–404.
37.Dr Hala S. Arif, Dr Rabab F. Thejeal, Dr Ahmed Farhan (2016) Inborn Errors of Metabolism Status in Iraq. Journal of Pharmacy and Biological Sciences 2016; Volume 11, Issue 2: PP 58-
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