Login Register Cart 0
Generic placeholder image

Current Pediatric Reviews

Editor-in-Chief

ISSN (Print): 1573-3963
ISSN (Online): 1875-6336

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Current Scenario of Clinical Diagnosis to Identify Inborn Errors of Metabolism with Precision Profiling for Expanded Screening in Infancy in a Resource-limited Setting

Author(s): Sukhes Mukherjee*, Ashwin Kotnis, Suman Kumar Ray, Kannan Vaidyanathan, Snighdha Singh and Rishabh Mittal

Volume 19, Issue 1, 2023

Published on: 14 June, 2022

Page: [34 - 47] Pages: 14

DOI: 10.2174/1573396318666220404113732

Price: $65

Abstract

Inborn errors of metabolism (IEM) are a diverse collection of abnormalities that cause a variety of morbidities and mortality in children and are classified as uncommon genetic diseases. Early and accurate detection of the condition can save a patient's life. By aiding families as they navigate the experience of having a child with an IEM, healthcare practitioners have the chance to reduce the burden of negative emotional consequences. New therapeutic techniques, such as enzyme replacement and small chemical therapies, organ transplantation, and cellular and gene-based therapies using whole-genome sequencing, have become available in addition to traditional medical intake and cofactor treatments. In the realm of metabolic medicine and metabolomics, the twentyfirst century is an exciting time to be alive. The availability of metabolomics and genomic analysis has led to the identification of a slew of novel diseases. Due to the rarity of individual illnesses, obtaining high-quality data for these treatments in clinical trials and real-world settings has proven difficult. Guidelines produced using standardized techniques have helped enhance treatment delivery and clinical outcomes over time. This article gives a comprehensive description of IEM and how to diagnose it in patients who have developed clinical signs early or late. The appropriate use of standard laboratory outcomes in the preliminary patient assessment is also emphasized that can aid in the ordering of specific laboratory tests to confirm a suspected diagnosis, in addition, to begin treatment as soon as possible in a resource limiting setting where genomic analysis or newborn screening facility is not available.

Keywords: Inborn errors of metabolism, newborn screening, genetic and metabolic disorders, treatment strategies, laboratory biomarkers, biochemical heterogeneity.

« Previous Next »
Graphical Abstract

[1]
Ray SK, Mukherjee S. Molecular and biochemical investigations of inborn errors of metabolism-altered redox homeostasis in branched-chain amino acid disorders, organic acidurias, and homocystinuria. Free Radic Res 2021; 55(6): 627-40.
[http://dx.doi.org/10.1080/10715762.2021.1877286] [PMID: 33504220]
[2]
Agana M, Frueh J, Kamboj M, Patel DR, Kanungo S. Common metabolic disorder (inborn errors of metabolism) concerns in primary care practice. Ann Transl Med 2018; 6(24): 469.
[http://dx.doi.org/10.21037/atm.2018.12.34] [PMID: 30740400]
[3]
Cox TM. Alkaptonuria: Leading to the treasure in exceptions. JIMD Rep 2012; 5: 49-57.
[http://dx.doi.org/10.1007/8904_2011_93] [PMID: 23430917]
[4]
Carlson LM, Vora NL. Prenatal diagnosis: Screening and diagnostic tools. Obstet Gynecol Clin North Am 2017; 44(2): 245-56.
[http://dx.doi.org/10.1016/j.ogc.2017.02.004] [PMID: 28499534]
[5]
Wilcox G. Impact of pregnancy on inborn errors of metabolism. Rev Endocr Metab Disord 2018; 19(1): 13-33.
[http://dx.doi.org/10.1007/s11154-018-9455-2] [PMID: 30198059]
[6]
Vaidyanathan K. Newborn screening for inborn errors of metabolism - Current status and challenges. Indian J Clin Biochem 2019; 34(1): 25.
[7]
Echeverri OY, Guevara JM, Espejo-Mojica ÁJ, et al. Research, diagnosis and education in inborn errors of metabolism in Colombia: 20 years’ experience from a reference center. Orphanet J Rare Dis 2018; 13(1): 141.
[http://dx.doi.org/10.1186/s13023-018-0879-2] [PMID: 30115094]
[8]
Waters D, Adeloye D, Woolham D, Wastnedge E, Patel S, Rudan I. Global birth prevalence and mortality from inborn errors of metabo-lism: A systematic analysis of the evidence. J Glob Health 2018; 8(2): 021102.
[http://dx.doi.org/10.7189/jogh.08.021102] [PMID: 30479748]
[9]
Pourfarzam M, Zadhoush F. Newborn Screening for inherited metabolic disorders; news and views. J Res Med Sci 2013; 18(9): 801-8.
[10]
Woidy M, Muntau AC, Gersting SW. Inborn errors of metabolism and the human interactome: A systems medicine approach. J Inherit Metab Dis 2018; 41(3): 285-96.
[http://dx.doi.org/10.1007/s10545-018-0140-0] [PMID: 29404805]
[11]
Ramsay J, Morton J, Norris M, Kanungo S. Organic acid disorders. Ann Transl Med 2018; 6(24): 472.
[http://dx.doi.org/10.21037/atm.2018.12.39] [PMID: 30740403]
[12]
Burton BK. Inborn errors of metabolism in infancy: A guide to diagnosis. Pediatrics 1998; 102(6): E69.
[http://dx.doi.org/10.1542/peds.102.6.e69] [PMID: 9832597]
[13]
Del Re S, Empain A, Vicinanza A, et al. Irritability, poor feeding and respiratory alkalosis in newborns: Think about metabolic emergencies. A brief summary of hyperammonemia management. Pediatr Rep 2020; 12(3): 77-85.
[http://dx.doi.org/10.3390/pediatric12030019] [PMID: 33113778]
[14]
Poretti A, Blaser SI, Lequin MH, et al. Neonatal neuroimaging findings in inborn errors of metabolism. J Magn Reson Imaging 2013; 37(2): 294-312.
[http://dx.doi.org/10.1002/jmri.23693] [PMID: 22566357]
[15]
Whybra C, Mengel E, Russo A, et al. Lysosomal storage disorder in non-immunological hydrops fetalis (NIHF): More common than assumed? Report of four cases with transient NIHF and a review of the literature. Orphanet J Rare Dis 2012; 7(1): 86.
[http://dx.doi.org/10.1186/1750-1172-7-86] [PMID: 23137060]
[16]
Guerrero RB, Salazar D, Tanpaiboon P. Laboratory diagnostic approaches in metabolic disorders. Ann Transl Med 2018; 6(24): 470.
[http://dx.doi.org/10.21037/atm.2018.11.05] [PMID: 30740401]
[17]
Aliu E, Kanungo S, Arnold GL. Amino acid disorders. Ann Transl Med 2018; 6(24): 471.
[http://dx.doi.org/10.21037/atm.2018.12.12] [PMID: 30740402]
[18]
Williams RA, Mamotte CD, Burnett JR. Phenylketonuria: An inborn error of phenylalanine metabolism. Clin Biochem Rev 2008; 29(1): 31-41.
[PMID: 18566668]
[19]
Sumaily KM, Mujamammi AH. Phenylketonuria: A new look at an old topic, advances in laboratory diagnosis, and therapeutic strategies. Int J Health Sci (Qassim) 2017; 11(5): 63-70.
[PMID: 29114196]
[20]
Wanders RJ. Metabolic and molecular basis of peroxisomal disorders: A review. Am J Med Genet A 2004; 126A(4): 355-75.
[http://dx.doi.org/10.1002/ajmg.a.20661] [PMID: 15098234]
[21]
Sharer JD. An overview of biochemical genetics. Curr Protoc Hum Genet 2016; 89: 17.1.1-17.1.16..
[http://dx.doi.org/10.1002/0471142905.hg1701s89]
[22]
Bonilla Guerrero R, Karen K, Denise S, et al. The porphyrias Pediatric endocrinology and inborn errors of metabolism. (2nd ed.), New York: McGraw Hill 2017.
[23]
Mohamed S. Recognition and diagnostic approach to acute metabolic disorders in the neonatal period. Sudan J Paediatr 2011; 11(1): 20-8.
[PMID: 27493302]
[24]
Fu X, Iga M, Kimura M, Yamaguchi S. Simplified screening for organic acidemia using GC/MS and dried urine filter paper: A study on neonatal mass screening. Early Hum Dev 2000; 58(1): 41-55.
[http://dx.doi.org/10.1016/S0378-3782(00)00053-0] [PMID: 10785335]
[25]
Narayanan MP, Vaidyanathan K, Vinayan KP, Vasudevan DM. Diagnosis of organic acidurias: Methylmalonic aciduria, propionic aciduria, isovaleric aciduria and maple syrup urine disease in children: Two years experience at a tertiary care centre. Indian J Clin Biochem 2011; 26(4): 347-53.
[http://dx.doi.org/10.1007/s12291-011-0111-9] [PMID: 23024469]
[26]
Raghuveer TS, Garg U, Graf WD. Inborn errors of metabolism in infancy and early childhood: An update. Am Fam Physician 2006; 73(11): 1981-90.
[PMID: 16770930]
[27]
Banta-Wright SA, Steiner RD. Tandem mass spectrometry in newborn screening: A primer for neonatal and perinatal nurses. J Perinat Neonatal Nurs 2004; 18(1): 41-58.
[http://dx.doi.org/10.1097/00005237-200401000-00005] [PMID: 15027667]
[28]
Mak CM, Lee HC, Chan AY, Lam CW. Inborn errors of metabolism and expanded newborn screening: Review and update. Crit Rev Clin Lab Sci 2013; 50(6): 142-62.
[http://dx.doi.org/10.3109/10408363.2013.847896] [PMID: 24295058]
[29]
Nolasco DM, Fortes ICP, Valadares ER. Quantitative analysis of amino acids by HPLC in dried blood and urine in the neonatal period: Establishment of reference values. Biomed Chromatogr 2020; 34(11): e4931.
[http://dx.doi.org/10.1002/bmc.4931] [PMID: 32588474]
[30]
Brosnan ME, Brosnan JT. Orotic acid excretion and arginine metabolism. J Nutr 2007; 137(6) (Suppl. 2): 1656S-61S.
[http://dx.doi.org/10.1093/jn/137.6.1656S] [PMID: 17513443]
[31]
Biswas A, Malhotra M, Mankad K, et al. Clinico-radiological phenotyping and diagnostic pathways in childhood neurometabolic disorders-a practical introductory guide. Transl Pediatr 2021; 10(4): 1201-30.
[http://dx.doi.org/10.21037/tp-20-335] [PMID: 34012862]
[32]
Wiwattanadittakul N, Prust M, Gaillard WD, et al. The utility of EEG monitoring in neonates with hyperammonemia due to inborn errors of metabolism. Mol Genet Metab 2018; 125(3): 235-40.
[http://dx.doi.org/10.1016/j.ymgme.2018.08.011] [PMID: 30197275]
[33]
Stradomska TJ, Syczewska M, Jamroz E, et al. Serum very long-chain fatty acids (VLCFA) levels as predictive biomarkers of diseases severity and probability of survival in peroxisomal disorders. PLoS One 2020; 15(9): e0238796.
[http://dx.doi.org/10.1371/journal.pone.0238796] [PMID: 32946460]
[34]
Jones CM, Smith M, Henderson MJ. Reference data for cerebrospinal fluid and the utility of amino acid measurement for the diagnosis of inborn errors of metabolism. Ann Clin Biochem 2006; 43(Pt 1): 63-6.
[http://dx.doi.org/10.1258/000456306775141759] [PMID: 16390611]
[35]
Kerkhofs MHPM, Haijes HA, Willemsen AM, et al. Cross-omics: Integrating genomics with metabolomics in clinical diagnostics. Metabolites 2020; 10(5): 206.
[http://dx.doi.org/10.3390/metabo10050206] [PMID: 32443577]
[36]
Kruszka P, Regier D. Inborn errors of metabolism: From preconception to adulthood. Am Fam Physician 2019; 99(1): 25-32.
[PMID: 30600976]
[37]
van Rijt WJ, Koolhaas GD, Bekhof J, et al. Inborn errors of metabolism that cause sudden infant death: A systematic review with implica-tions for population neonatal screening programmes. Neonatology 2016; 109(4): 297-302.
[http://dx.doi.org/10.1159/000443874] [PMID: 26907928]
[38]
Chakrapani A, Cleary MA, Wraith JE. Detection of inborn errors of metabolism in the newborn. Arch Dis Child Fetal Neonatal Ed 2001; 84(3): F205-10.
[http://dx.doi.org/10.1136/fn.84.3.F205] [PMID: 11320051]
[39]
Shawky RM, El-Din Riad MS, Osman HM, Bahaa NM. Screening for some inborn errors of amino acid metabolism which impair mental function. Egypt J Med Hum Genet 2001; 2: 71-91.
[40]
Shawky RM, Abd-Elkhalek HS, Elakhdar SE. Selective screening in neonates suspected to have inborn errors of metabolism. Egypt J Med Hum Genet 2015; 16(2): 165-71.
[http://dx.doi.org/10.1016/j.ejmhg.2015.01.003]
[41]
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 Pediatr 2012; 12(1): 18.
[http://dx.doi.org/10.1186/1471-2431-12-18] [PMID: 22364411]
[42]
Nongalleima K, Ajungla T, Singh CB. GCMS based metabolic profiling of essential oil of Citrus macroptera Montruz, leaves and peel, assessment of in vitro antioxidant and anti-inflammatory activity. Int J Pharm Pharm Sci 2017; 9(9): 107-14.
[http://dx.doi.org/10.22159/ijpps.2017v9i9.19593]
[43]
Zerrouki K, Djebli N, Ozkan EE, Ozsoy N, Gul O, Mat A. Hypericum perforatum improve memory and learning in Alzheimer’s model: Experimental study in Mice. Int J Pharm Pharm Sci 2016; 8: 49-57.
[44]
Shafie AA, Supian A, Ahmad Hassali MA, et al. Rare disease in Malaysia: Challenges and solutions. PLoS One 2020; 15(4): e0230850.
[http://dx.doi.org/10.1371/journal.pone.0230850] [PMID: 32240232]
[45]
Harthan AA. An introduction to pharmacotherapy for inborn errors of metabolism. J Pediatr Pharmacol Ther 2018; 23(6): 432-46.
[http://dx.doi.org/10.5863/1551-6776-23.6.432] [PMID: 30697128]
[46]
van der Knaap JA, Verrijzer CP. Undercover: Gene control by metabolites and metabolic enzymes. Genes Dev 2016; 30(21): 2345-69.
[http://dx.doi.org/10.1101/gad.289140.116] [PMID: 27881599]
[47]
Leonard JV. Komrower lecture: Treatment of inborn errors of metabolism: A review. J Inherit Metab Dis 2006; 29(2-3): 275-8.
[http://dx.doi.org/10.1007/s10545-006-0273-4] [PMID: 16763887]
[48]
Hartog AW, Franken R, Zwinderman AH, Groenink M, Mulder BJ. Current and future pharmacological treatment strategies with regard to aortic disease in Marfan syndrome. Expert Opin Pharmacother 2012; 13(5): 647-62.
[http://dx.doi.org/10.1517/14656566.2012.665446] [PMID: 22397493]
[49]
Boyer SW, Barclay LJ, Burrage LC. Inherited metabolic disorders: Aspects of chronic nutrition management. Nutr Clin Pract 2015; 30(4): 502-10.
[http://dx.doi.org/10.1177/0884533615586201] [PMID: 26079521]
[50]
Suzuki I, Yamauchi T, Onuma M, Nozaki S. Allopurinol, an inhibitor of uric acid synthesis-can it be used for the treatment of metabolic syndrome and related disorders? Drugs Today (Barc) 2009; 45(5): 363-78.
[http://dx.doi.org/10.1358/dot.2009.45.5.1377598] [PMID: 19584965]
[51]
Chinsky JM, Singh R, Ficicioglu C, et al. Diagnosis and treatment of tyrosinemia type I: A US and Canadian consensus group review and recommendations. Genet Med 2017; 19(12): 1380-95.
[http://dx.doi.org/10.1038/gim.2017.101] [PMID: 28771246]
[52]
Kishnani PS, Steiner RD, Bali D, et al. Pompe disease diagnosis and management guideline. Genet Med 2006; 8(5): 267-88.
[http://dx.doi.org/10.1097/01.gim.0000218152.87434.f3] [PMID: 16702877]
[53]
Kishnani PS, Austin SL, Abdenur JE, et al. American College of Medical Genetics and Genomics. Diagnosis and management of glycogen storage disease type I: A practice guideline of the American College of Medical Genetics and Genomics. Genet Med 2014; 16(11): e1-e29.
[http://dx.doi.org/10.1038/gim.2014.128] [PMID: 25356975]
[54]
Manta-Vogli PD, Schulpis KH, Dotsikas Y, Loukas YL. Nutrition and medical support during pregnancy and lactation in women with inborn errors of intermediary metabolism disorders (IEMDs). J Pediatr Endocrinol Metab 2020; 33(1): 5-20.
[http://dx.doi.org/10.1515/jpem-2019-0048] [PMID: 31804959]
[55]
Roberts SA, Dong B, Firrman JA, Moore AR, Sang N, Xiao W. Engineering factor Viii for hemophilia gene therapy. J Genet Syndr Gene Ther 2011; 1: S1-S006.
[PMID: 23565342]
[56]
Samelson-Jones BJ, Arruda VR. Protein-engineered coagulation factors for hemophilia gene therapy. Mol Ther Methods Clin Dev 2018; 12: 184-201.
[http://dx.doi.org/10.1016/j.omtm.2018.12.007] [PMID: 30705923]
[57]
Karponi G, Zogas N. Gene therapy for beta-thalassemia: Updated perspectives. Appl Clin Genet 2019; 12: 167-80.
[http://dx.doi.org/10.2147/TACG.S178546] [PMID: 31576160]
[58]
Iansante V, Chandrashekran A, Dhawan A. Cell-based liver therapies: Past, present and future. Philos Trans R Soc Lond B Biol Sci 2018; 373(1750): 20170229.
[http://dx.doi.org/10.1098/rstb.2017.0229]
[59]
Chandler RJ, Venditti CP. Gene therapy for metabolic diseases. Transl Sci Rare Dis 2016; 1(1): 73-89.
[http://dx.doi.org/10.3233/TRD-160007] [PMID: 27853673]
[60]
Schneller JL, Lee CM, Bao G, Venditti CP. Genome editing for inborn errors of metabolism: Advancing towards the clinic. BMC Med 2017; 15(1): 43.
[http://dx.doi.org/10.1186/s12916-017-0798-4] [PMID: 28238287]
[61]
Ginocchio VM, Ferla R, Auricchio A, Brunetti-Pierri N. Current status on clinical development of adeno-associated virus-mediated liver-directed gene therapy for inborn errors of metabolism. Hum Gene Ther 2019; 30(10): 1204-10.
[http://dx.doi.org/10.1089/hum.2019.151] [PMID: 31517544]
[62]
Fukao T, Nakamura K. Advances in inborn errors of metabolism. J Hum Genet 2019; 64(2): 65.
[http://dx.doi.org/10.1038/s10038-018-0535-7] [PMID: 30679804]
[63]
Rutten MGS, Rots MG, Oosterveer MH. Exploiting epigenetics for the treatment of inborn errors of metabolism. J Inherit Metab Dis 2020; 43(1): 63-70.
[http://dx.doi.org/10.1002/jimd.12093] [PMID: 30916397]
[64]
Mordaunt D, Cox D, Fuller M. Metabolomics to improve the diagnostic efficiency of inborn errors of metabolism. Int J Mol Sci 2020; 21(4): 1195.
[http://dx.doi.org/10.3390/ijms21041195] [PMID: 32054038]
[65]
Macleod EL, Ney DM. Nutritional management of phenylketonuria. Ann Nestle [Eng] 2010; 68(2): 58-69.
[http://dx.doi.org/10.1159/000312813] [PMID: 22475869]
[66]
Zhou X, Cui Y, Han J. Methylmalonic acidemia: Current status and research priorities. Intractable Rare Dis Res 2018; 7(2): 73-8.
[http://dx.doi.org/10.5582/irdr.2018.01026] [PMID: 29862147]
[67]
Morris AA, Kožich V, Santra S, et al. Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency. J Inherit Metab Dis 2017; 40(1): 49-74.
[http://dx.doi.org/10.1007/s10545-016-9979-0] [PMID: 27778219]
[68]
Oishi K, Arnon R, Wasserstein MP, Diaz GA. Liver transplantation for pediatric inherited metabolic disorders: Considerations for indica-tions, complications, and perioperative management. Pediatr Transplant 2016; 20(6): 756-69.
[http://dx.doi.org/10.1111/petr.12741] [PMID: 27329540]
[69]
Tebani A, Afonso C, Marret S, Bekri S. Omics-based strategies in precision medicine: Toward a paradigm shift in inborn errors of metabolism investigations. Int J Mol Sci 2016; 17(9): 1555.
[http://dx.doi.org/10.3390/ijms17091555] [PMID: 27649151]
[70]
Karczewski KJ, Snyder MP. Integrative omics for health and disease. Nat Rev Genet 2018; 19(5): 299-310.
[http://dx.doi.org/10.1038/nrg.2018.4] [PMID: 29479082]
[71]
Lee H, Deignan JL, Dorrani N, et al. Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA 2014; 312(18): 1880-7.
[http://dx.doi.org/10.1001/jama.2014.14604] [PMID: 25326637]
[72]
Lamari F, Mochel F, Saudubray JM. An overview of inborn errors of complex lipid biosynthesis and remodelling. J Inherit Metab Dis 2015; 38(1): 3-18.
[http://dx.doi.org/10.1007/s10545-014-9764-x] [PMID: 25238787]
[73]
Boczonadi V, Jennings MJ, Horvath R. The role of tRNA synthetases in neurological and neuromuscular disorders. FEBS Lett 2018; 592(5): 703-17.
[http://dx.doi.org/10.1002/1873-3468.12962] [PMID: 29288497]
[74]
Goetz LH, Schork NJ. Personalized medicine: Motivation, challenges, and progress. Fertil Steril 2018; 109(6): 952-63.
[http://dx.doi.org/10.1016/j.fertnstert.2018.05.006] [PMID: 29935653]
[75]
Shlomi T, Cabili MN, Ruppin E. Predicting metabolic biomarkers of human inborn errors of metabolism. Mol Syst Biol 2009; 5(1): 263.
[http://dx.doi.org/10.1038/msb.2009.22] [PMID: 19401675]
[76]
Vaidyanathan K, Gopalakrishnan S. Novel biomarkers for inborn errors of metabolism in the metabolomics era. IJBB 2018; 55: 314-20.
[77]
Finsterer J, Zarrouk-Mahjoub S. Biomarkers for detecting mitochondrial disorders. J Clin Med 2018; 7(2): 7.
[http://dx.doi.org/10.3390/jcm7020016] [PMID: 29385732]
[78]
Ries M, Schaefer E, Lührs T, et al. Critical assessment of chitotriosidase analysis in the rational laboratory diagnosis of children with Gaucher disease and Niemann-Pick disease type A/B and C. J Inherit Metab Dis 2006; 29(5): 647-52.
[http://dx.doi.org/10.1007/s10545-006-0363-3] [PMID: 16972172]
[79]
Vaidyanathan K, Vasudevan DM. The challenge of metabolic disorders in India. Amala Res Bull 2009; 27: 278-84.
[80]
Vaidyanathan K. Urinary proteomics and metabolomics in the diagnosis of pediatric disorders. Proteomics Clin Appl 2015; 9(5-6): 482-9.
[http://dx.doi.org/10.1002/prca.201400093] [PMID: 25631340]

Rights & Permissions Print Cite
Article Metrics
3
© 2024 Bentham Science Publishers | Privacy Policy