Characteristic clinical features and laboratory findings of inborn errors of metabolism
Authors:
H. Kolářová; T. Honzík
Authors place of work:
Klinika dětského a dorostového lékařství 1. LF UK a VFN, Praha
Published in the journal:
Čes-slov Pediat 2018; 73 (6): 348-364.
Summary
Introduction:
Inborn Errors of Metabolism (IEM) represent a group of >1000 rare genetic disorders that are caused by a defect of single/multiple enzymes or changes in structural, assembling and transporting proteins that participate in metabolic pathways. Since any system can be affected, variable clinical symptoms may occur, leading to a diagnostic delay.
Aim:
To provide clear overview of the main key clinical and laboratory findings of IEM encountered by both primary health care or hospital physicians – pediatricians.
Results:
Main clinical features of IEM are represented by developmental regression, pharmacoresistant epilepsy, cardiomyopathy, myopathic syndrome or muscle pain in rhabdomyolysis and hepato-/splenomegaly. As much as 70% of a childhood urolithiasis are caused by one of the IEM. Detailed ophthalmic examination may reveal corneal clouding or cataract, ophthalmoplegia, pigmentary retinopathy and optic neuropathy. Some of the symptoms may be helpful in making the right diagnosis faster at a glance, such as craniofacial dysmorphism, hypertrichosis, atypical structure of adnexa and some bone changes. The main laboratory abnormalities include hypoglycemia, hyperammonemia, dyslipidemia and (cholestatic) hepatopathy. Standardized cerebrospinal fluid examination is crucial for the diagnosis of some of the IEM that can be potentially treatable.
Conclusion:
Although individual IEM are considered rare, their estimated total prevalence is higher than 1:200. It is therefore very likely, that most physicians will experience at least one of the IEM in their lifetime. Setting up the correct diagnosis is of utmost importance for initiating therapy as for genetic and prenatal counselling.
Key words:
inborn errors of metabolism, developmental regression, cardiomyopathy, myopathy, rhabdomyolysis, hepatopathy, hepato-/splenomegaly, urolithiasis, optic neuropathy, dysostosis multiplex, hypoglycaemia, hyper- ammonemia, dyslipidemia
Zdroje
1. Nordestgaard BG, Chapman MJ, Humphries SE, et al.; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J 2013; 34 (45): 3478–3490a.
2. Honzik T, Zeman J. Dědičné metabolické poruchy v dětském věku. 1. vyd. Praha: Institut postgraduálního vzdělávání ve zdravotnictví, 2013: 13–93.
3. Honzik T, Zeman J. Dědičné poruchy metabolismu v kazuistikách. In: Honzik T, Zeman J et al (Eds). Dědičné poruchy metabolismu v kazuistikách. 1. vyd. Praha: Mladá fronta, 2016: 3–27.
3. Lipshultz SE, Sleeper LA, Towbin JA, et al. The incidence of pediatric cardiomyopathy in two regions of the United States. N Engl J Med 2003; 348: 1647–1655.
4. Nugent AW, Daubeney PE, Chondros P, et al. National Australian Childhood Cardiomyopathy Study. The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med 2003; 348: 1639–1646.
5. Kindel SJ, Miller EM, Gupta R. Pediatric cardiomyopathy: importance of genetic and metabolic evaluation. J Card Fail 2012 May; 18 (5): 396–403.
6. Byers SL, Ficicioglu C. Infant with cardiomyopathy: When to suspect inborn errors of metabolism? World J Cardiol 2014 November 26; 6 (11): 1149–1155.
7. Honzik T, Tesarova M, Mayr J, et al. Mitochondrial encephalocardiomyopathy with early neonatal onset due to TMEM70 mutation. Arch Dis Child 2010 Apr; 95 (4): 296–301.
8. Honzik T, Tesarova M, Magner M, et al. Neonatal onset of mitochondrial disorders in 129 patients: clinical and laboratory characteristics and a new approach to diagnosis. J Inherit Metab Dis 2012; 35 (5): 749–759.
9. Mazurová S, Tesařová M, Magner M, et al. Novel mutations in the TAZ gene in patients with Barth syndrome. Liver Transpl 2016; 22 (5): 677–685.
10. Wiseman DH, Mercer J, Tylee K, et al. Management of mucopolysaccharidosis type IH (Hurler‘s syndrome) presenting in infancy with severe dilated cardiomyopathy: a single institution‘s experience. J Inherit Metab Dis 2013 Mar; 36 (2): 263–270.
11. Seemanová E. Dysmorfické příznaky – klíč v diagnostice genetických poruch. Pediatr pro Praxi 2008; 9 (5): 305–308.
12. Ng BG, Freeze HH. Perspectives on glycosylation and its congenital disorders. Trends Genet 2018 Jun; 34 (6): 466–476. doi: 10.1016/j.tig.2018.03.002. Epub 2018 Mar 29. Review.
13. Taylor SA, Whitington PF. Neonatal acute liver failure. Liver Transpl 2016; 22 (5): 677–685.
14. Bonilla S, Prozialeck JD, Malladi P, et al. Neonatal iron overload and tissue siderosis due to gestational alloimmune liver disease. J Hepatol 2012; 56 (6): 1351–1355.
15. De Castro M, Johnston J, Biesecker L. Determining the prevalence of McArdle disease from gene frequency by analysis of next-generation sequencing data. Genet Med 2015; 17 (12): 1002–1006.
16. Clarkson PM, Eichner ER. Exertional rhabdomyolysis: does elevated blood creatine kinase foretell renal failure? Curr Sports Med Rep 2006 Apr; 5 (2): 57–60.
17. Lappalainen H, Tiula E, Uotila L, et al. Elimination kinetics of myoglobin and creatine kinase in rhabdomyolysis: implications for follow-up. Crit Care Med 2002; 30 (10): 2212–2215
Štítky
Neonatology Paediatrics General practitioner for children and adolescentsČlánok vyšiel v časopise
Czech-Slovak Pediatrics
2018 Číslo 6
- What Effect Can Be Expected from Limosilactobacillus reuteri in Mucositis and Peri-Implantitis?
- The Importance of Limosilactobacillus reuteri in Administration to Diabetics with Gingivitis
Najčítanejšie v tomto čísle
- Characteristic clinical features and laboratory findings of inborn errors of metabolism
- A complex view of vitamin B12 deficiency in childhood
- Newborn screening of inherited metabolic diseases in the Czech Republic
- Lysosomal storage disorders – development of diagnostic process and treatment in Slovakia