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Neurometabolic Disorders

  • Sarar MohamedEmail author
  • Mustafa A. M. Salih
Chapter
  • 106 Downloads

Abstract

Inborn errors of metabolism (IEM) are inherited diseases that result mainly from single gene defects leading to deficiency of a protein in the form of an enzyme or a cofactor. Neurometabolic disorders constitute a group of IEM that present with predominant neurological manifestations if untreated. Broadly, neurometabolic disorders can be classified into three major groups: disorders of intermediary metabolism, disorders of complex molecules, and neurotransmitter disorders. Neurometabolic disorders may affect a specific part of the central or peripheral nervous system such as extrapyramidal tracts, basal ganglia, spinal cord, or lower motor unit. They present with a variety of neurological symptoms and signs. These range from isolated epilepsy to constellation of features suggestive of acute encephalopathy, chronic encephalopathy, and/or movement disorder. When a neurometabolic disease is suspected, baseline investigations such as blood gas, glucose, lactate, and ammonia may direct the physician toward the possible etiology of the disease. Further investigations like serum amino acids, acylcarnitine profile, and urine organic acids may pinpoint the diagnosis, which may ultimately be confirmed by an enzyme assay or a molecular study. Early diagnosis and appropriate management of neurometabolic disorders are often associated with a favorable outcome, especially in the neonatal period. Effective management strategies may include supportive care, removal of toxic metabolites, and provision of adequate calories and dietary intervention, together with introduction of specific drugs, chaperones, enzyme replacement therapy, and stem cell and liver transplant when indicated.

Keywords

Inborn errors of metabolism Diagnosis Genetics Metabolic disorders Neurometabolic disorder Treatment 

Supplementary material

Video 14.1

Video EEG of a baby with nonketotic hyperglycinemia manifesting infantile epileptic encephalopathy and hiccups. The baby was unconscious and the record showed prolonged suppression followed by a short period of bursts of generalized discharges of spikes/polyspikes and sharp waves and slow waves (burst-suppression pattern) associated with violent flexor spasms. Inter-burst-interval (suppression period) was much longer and the baby was motionless. In one occasion, the baby developed tonic posturing of the right hand with continuous ictal discharges on the left hemisphere followed by complete inactivation in the right upper limb (MPG 12818 kb)

Video 14.2

A baby with GM2 Gangliosidosis (Sandhoff disease) showing ankle clonus as a feature of hyperreflexia (AVI 12060 kb)

Video 14.3

A child with GM2 Gangliosidosis (Tay-Sachs disease) showing startle reactions to loud sound (AVI 9475 kb)

Video 14.4

Choreic movements in a child with neuronal ceroid lipofuscinosis (CLN) type 7 (CLN7) (AVI 3008 kb)

Video 14.5

Myoclonic jerks in a child with neuronal ceroid lipofuscinosis (CLN) type 14 (CLN14) (AVI 14605 kb)

Video 14.6

Hyperekplexia in a neonate with neuronal ceroid lipofuscinosis (CLN) type 10 (CLN10). There is remarkable exaggerated startle to tactile and acoustic stimuli (tapping the nose, touch, and sound) (MPG 49012 kb)

Video 14.7

A child with Lesch-Nyhan syndrome showing extrapyramidal signs in the form of very large amplitude, jerky gross motor movements (ballism). The left upper limb was stranded to prevent self-injury (AVI 3327 kb)

References

  1. 1.
    Mohamed S, El Melegy EM, Talaat I, Hosny A, Abu-Amero KK. Neurometabolic disorders-related early childhood epilepsy: a single-center experience in Saudi Arabia. Pediatr Neonatol. 2015;56:393–401.PubMedCrossRefGoogle Scholar
  2. 2.
    Scriver C, Beaudet AL, Sly WS, Valle D, Vogelstein B, Childs B, editors. The metabolic and molecular bases of inherited diseases. 8th ed. New York: McGraw-Hill Medical; 2001.Google Scholar
  3. 3.
    Clarke JTR. A clinical guide to inherited metabolic diseases. 3rd ed. Cambridge, New York: Cambridge University Press; 2010.Google Scholar
  4. 4.
    Saudubray J-M, Baumgartner MR, Walter J, editors. Inborn metabolic diseases: diagnosis and treatment. 6th ed. New York, NY: Springer; 2016.Google Scholar
  5. 5.
    Hoffmann GF, Zschocke J, Nyhan WL, editors. Inherited metabolic diseases: a clinical approach. 2nd ed. New York, NY: Springer; 2016.Google Scholar
  6. 6.
    Thöny B, Duran M, Gibson KM, Dionisi-Vici C, editors. Physician’s guide to the diagnosis, treatment, and follow-up of inherited metabolic diseases. 1st ed. Berlin: Springer; 2006.Google Scholar
  7. 7.
    Granata T. Chapter 30: Metabolic and degenerative disorders. In: Theodore WH, editor. Handbook of clinical neurology. Amsterdam: Elsevier. p. 485–511.Google Scholar
  8. 8.
    Mohamed S, El-Khodary H, Khalifa N, Hellani A, El-Kholy S, El-Melegy E, et al. Pattern of metabolic disorders presenting to pediatric and metabolic clinics in developing countries. Res J Med Med Sci. 2009;4:14–9.Google Scholar
  9. 9.
    Mohamed S. Recognition and diagnostic approach to acute metabolic disorders in the neonatal period. Sudan J Paediatr. 2011;11:20–8.PubMedPubMedCentralGoogle Scholar
  10. 10.
    Filiano JJ. Neurometabolic diseases in the newborn. Clin Perinatol. 2006;33:411–79.PubMedCrossRefGoogle Scholar
  11. 11.
    Van Hove JLK, Lohr NJ. Metabolic and monogenic causes of seizures in neonates and young infants. Mol Genet Metab. 2011;104:214–30.PubMedCrossRefGoogle Scholar
  12. 12.
    Levy PA. Inborn errors of metabolism: part 1: overview. Pediatr Rev. 2009;30:131–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Levy PA. Inborn errors of metabolism: part 2: specific disorders. Pediatr Rev. 2009;30:e22–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Kamboj M. Clinical approach to the diagnoses of inborn errors of metabolism. Pediatr Clin N Am. 2008;55:1113–27, viiiCrossRefGoogle Scholar
  15. 15.
    Leach EL, Shevell M, Bowden K, Stockler-Ipsiroglu S, van Karnebeek CDM. Treatable inborn errors of metabolism presenting as cerebral palsy mimics: systematic literature review. Orphan J Rare Dis. 2014;9:197.CrossRefGoogle Scholar
  16. 16.
    Masri A, Wahsh SA. Manifestations and treatment of epilepsy in children with neurometabolic disorders: a series from Jordan. Seizure. 2014;23:10–5.PubMedCrossRefGoogle Scholar
  17. 17.
    Alfadhel M, Al-Thihli K, Moubayed H, Eyaid W, Al-Jeraisy M. Drug treatment of inborn errors of metabolism: a systematic review. Arch Dis Child. 2013;98:454–61.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Mohamed S. Treatment strategies for acute metabolic disorders in neonates. Sudan J Paediatr. 2011;11:6–13.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Alfadhel M, Benmeakel M, Hossain MA, Al Mutairi F, Al Othaim A, Alfares AA, et al. Thirteen year retrospective review of the spectrum of inborn errors of metabolism presenting in a tertiary center in Saudi Arabia. Orphan J Rare Dis. 2016;11:126.CrossRefGoogle Scholar
  20. 20.
    Moammar H, Cheriyan G, Mathew R, Al-Sannaa N. Incidence and patterns of inborn errors of metabolism in the Eastern Province of Saudi Arabia, 1983–2008. Ann Saudi Med. 2010;30:271–7.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Salih MAM. Genetic disorders in Sudan. In: Teebi AS, editor. Genetic disorders among Arab populations. Berlin, Heidelberg: Springer. p. 575–612.Google Scholar
  22. 22.
    Al-Hassnan ZN, Sakati N. Genetic disorders in Saudi Arabia. In: Teebi AS, editor. Genetic disorders among Arab populations. Berlin, Heidelberg: Springer. p. 531–73.Google Scholar
  23. 23.
    Alkuraya FS. Genetics and genomic medicine in Saudi Arabia. Mol Genet Genomic Med. 2014;2:369–78.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Moorthie S, Cameron L, Sagoo GS, Bonham JR, Burton H. Systematic review and meta-analysis to estimate the birth prevalence of five inherited metabolic diseases. J Inherit Metab Dis. 2014;37:889–98.PubMedCrossRefGoogle Scholar
  25. 25.
    Teebi AS. Introduction: genetic diversity among Arabs. In: Teebi AS, editor. Genetic disorders among Arab populations. Berlin, Heidelberg: Springer. p. 3–34.Google Scholar
  26. 26.
    Fitzpatrick D. Inborn errors of metabolism in the newborn: clinical presentation and investigation. J Roy College Phys Edinb. 2006;36:147–51.Google Scholar
  27. 27.
    Saudubray J-M, Sedel F, Walter JH. Clinical approach to treatable inborn metabolic diseases: an introduction. J Inherit Metab Dis. 2006;29:261–74.PubMedCrossRefGoogle Scholar
  28. 28.
    Strauss KA, Puffenberger EG, Morton DH. Maple syrup urine disease. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1319/. Accessed 19 Feb 2017.Google Scholar
  29. 29.
    Simon E, Fingerhut R, Baumkötter J, Konstantopoulou V, Ratschmann R, Wendel U. Maple syrup urine disease: favourable effect of early diagnosis by newborn screening on the neonatal course of the disease. J Inherit Metab Dis. 2006;29:532–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Blau N, Hennermann JB, Langenbeck U, Lichter-Konecki U. Diagnosis, classification, and genetics of phenylketonuria and tetrahydrobiopterin (BH4) deficiencies. Mol Genet Metab. 2011;104(Suppl):S2–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Zschocke J, Hofmann GF. Vademecum metabolicum: diagnosis and treatment of inborn errors of metabolism. 3rd ed. Friedrichsdorf: Schattauer Gmbh; 2011.Google Scholar
  32. 32.
    Mohamed S, Elmeleagy E, Khan U, Hellani A. Classical phenylketonuria and Antley-Bixler syndrome co-exist in a patient. Med J Cairo Univ. 2008;76:165–7.Google Scholar
  33. 33.
    Regier DS, Greene CL. Phenylalanine hydroxylase deficiency. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1504/. Accessed 20 Feb 2017.Google Scholar
  34. 34.
    Ah Mew N, Lanpher BC, Gropman A, Chapman KA, Simpson KL, Urea Cycle Disorders Consortium, et al. Urea cycle disorders overview. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1217/. Accessed 20 Feb 2017.Google Scholar
  35. 35.
    Burgard P, Kölker S, Haege G, Lindner M, Hoffmann GF. Neonatal mortality and outcome at the end of the first year of life in early onset urea cycle disorders—review and meta-analysis of observational studies published over more than 35 years. J Inherit Metab Dis. 2016;39:219–29.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Clay AS, Hainline BE. Hyperammonemia in the ICU. Chest. 2007;132:1368–78.PubMedCrossRefGoogle Scholar
  37. 37.
    Häberle J, Boddaert N, Burlina A, Chakrapani A, Dixon M, Huemer M, et al. Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphan J Rare Dis. 2012;7:32.CrossRefGoogle Scholar
  38. 38.
    De Castro-Hamoy LG, Chiong MA, Estrada SC, Cordero CP. Challenges in the management of patients with maple syrup urine disease diagnosed by newborn screening in a developing country. J Commun Genet. 2017;8(1):9.CrossRefGoogle Scholar
  39. 39.
    Blau N, van Spronsen FJ, Levy HL. Phenylketonuria. Lancet. 2010;376:1417–27.PubMedCrossRefGoogle Scholar
  40. 40.
    Wettstein S, Underhaug J, Perez B, Marsden BD, Yue WW, Martinez A, et al. Linking genotypes database with locus-specific database and genotype-phenotype correlation in phenylketonuria. Eur J Hum Genet. 2015;23:302–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Picker JD, Levy HL. Homocystinuria caused by cystathionine beta-synthase deficiency. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1524/. Accessed 20 Feb 2017.Google Scholar
  42. 42.
    El-Said MF, Badii R, Bessisso MS, Shahbek N, El-Ali MG, El-Marikhie M, et al. A common mutation in the CBS gene explains a high incidence of homocystinuria in the Qatari population. Hum Mutat. 2006;27:719.PubMedCrossRefGoogle Scholar
  43. 43.
    Adam S, Almeida MF, Carbasius Weber E, Champion H, Chan H, Daly A, et al. Dietary practices in pyridoxine non-responsive homocystinuria: a European survey. Mol Genet Metab. 2013;110:454–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Salih MA, Bosley TM, Alorainy IA, Sabry MA, Rashed MS, Al-Yamani EA, et al. Preimplantation genetic diagnosis in isolated sulfite oxidase deficiency. Can J Neurol Sci. 2013;40:109–12.PubMedCrossRefGoogle Scholar
  45. 45.
    Bosley TM, Alorainy IA, Oystreck DT, Hellani AM, Seidahmed MZ, Osman MF, et al. Neurologic injury in isolated sulfite oxidase deficiency. The Canadian journal of neurological sciences. J Can Sci Neurol. 2014;41(1):42–8.CrossRefGoogle Scholar
  46. 46.
    Van Hove J, Coughlin C, Scharer G. Glycine encephalopathy. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1357/. Accessed 20 Feb 2017.Google Scholar
  47. 47.
    Haider N, Salih MA, Al-Rasheed S, Al-Mofada S, Krahn PM, Kabiraj M. Nonketotic hyperglycinemia: a life-threatening disorder in Saudi newborns. Ann Saudi Med. 1996;16:400–4.PubMedCrossRefGoogle Scholar
  48. 48.
    Mohamed S, Hamad MH, Kondkar AA, Abu-Amero KK. A novel mutation in ornithine transcarbamylase gene causing mild intermittent hyperammonemia. Saudi Med J. 2015;36:1229–32.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Lichter-Konecki U, Caldovic L, Morizono H, Simpson K. Ornithine transcarbamylase deficiency. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK154378/. Accessed 20 Feb 2017.Google Scholar
  50. 50.
    Diaz GA, Krivitzky LS, Mokhtarani M, Rhead W, Bartley J, Feigenbaum A, et al. Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate. Hepatology. 2013;57:2171–9.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Quinonez SC, Thoene JG. Citrullinemia type I. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1458/. Accessed 20 Feb 2017.Google Scholar
  52. 52.
    Nagamani SCS, Erez A, Lee B. Argininosuccinate lyase deficiency. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK51784/. Accessed 20 Feb 2017.Google Scholar
  53. 53.
    Wong D, Cederbaum S, Crombez EA. Arginase deficiency. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1159/. Accessed 20 Feb 2017.Google Scholar
  54. 54.
    Al Kaabi EH, El-Hattab AW. N-acetylglutamate synthase deficiency: novel mutation associated with neonatal presentation and literature review of molecular and phenotypic spectra. Molecul Genet Metabol Rep. 2016;8:94–8.Google Scholar
  55. 55.
    Shchelochkov OA, Carrillo N, Venditti C. Propionic acidemia. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK92946/. Accessed 20 Feb 2017.Google Scholar
  56. 56.
    Schwahn BC, Pieterse L, Bisset WM, Galloway PG, Robinson PH. Biochemical efficacy of N-carbamylglutamate in neonatal severe hyperammonaemia due to propionic acidaemia. Eur J Pediatr. 2010;169:133–4.PubMedCrossRefGoogle Scholar
  57. 57.
    Mohamed S, Hamad MH, Abu-Amero KK. Identification of 2 novel homozygous mutations in the methylmalonyl-CoA mutase gene in Saudi patients. Saudi Med J. 2015;36:1110–4.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Manoli I, Sloan JL, Venditti CP. Isolated methylmalonic acidemia. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1231/. Accessed 20 Feb 2017.Google Scholar
  59. 59.
    Dionisi-Vici C, Deodato F, Röschinger W, Rhead W, Wilcken B. ‘Classical’ organic acidurias, propionic aciduria, methylmalonic aciduria and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry. J Inherit Metab Dis. 2006;29:383–9.PubMedCrossRefGoogle Scholar
  60. 60.
    Mohamed S, Hamad MH, Hassan HH, Salih MA. Glutaric aciduria type 1 as a cause of dystonic cerebral palsy. Saudi Med J. 2015;36:1354–7.PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Heringer J, Boy SPN, Ensenauer R, Assmann B, Zschocke J, Harting I, et al. Use of guidelines improves the neurological outcome in glutaric aciduria type I. Ann Neurol. 2010;68:743–52.PubMedCrossRefGoogle Scholar
  62. 62.
    Pfeil J, Listl S, Hoffmann GF, Kölker S, Lindner M, Burgard P. Newborn screening by tandem mass spectrometry for glutaric aciduria type 1: a cost-effectiveness analysis. Orphan J Rare Dis. 2013;8:167.CrossRefGoogle Scholar
  63. 63.
    Martín MA, Lucía A, Arenas J, Andreu AL. Glycogen storage disease type V. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1344/. Accessed 20 Feb 2017.Google Scholar
  64. 64.
    Wang D, Pascual JM, De Vivo D. Glucose transporter type 1 deficiency syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1430/. Accessed 20 Feb 2017.Google Scholar
  65. 65.
    Patel KP, O'Brien TW, Subramony SH, Shuster J, Stacpoole PW. The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab. 2012;105(1):34–43.PubMedCrossRefGoogle Scholar
  66. 66.
    Wang D, De Vivo D. Pyruvate carboxylase deficiency. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK6852/. Accessed 20 Feb 2017.Google Scholar
  67. 67.
    Chinnery PF. Mitochondrial disorders overview. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1224/. Accessed 20 Feb 2017.Google Scholar
  68. 68.
    Mohamed S, Alzagal A, Elmelegy E. Complex 1 respiratory chain disorder presenting with severe dilated cardiomyopathy and severe renal tubular acidosis. Med J Cairo Univ. 2008;76:359–61.Google Scholar
  69. 69.
    Dimauro S, Rustin P. A critical approach to the therapy of mitochondrial respiratory chain and oxidative phosphorylation diseases. Biochim Biophys Acta. 2009;1792:1159–67.PubMedCrossRefGoogle Scholar
  70. 70.
    Di Mauro S, Hirano M. MELAS. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1233/. Accessed 20 Feb 2017.Google Scholar
  71. 71.
    Santa KM. Treatment options for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Pharmacotherapy. 2010;30:1179–96.PubMedCrossRefGoogle Scholar
  72. 72.
    Hirano M. Mitochondrial neurogastrointestinal encephalopathy disease. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1179/. Accessed 20 Feb 2017.Google Scholar
  73. 73.
    Kozak I, Oystreck DT, Abu-Amero KK, Nowilaty SR, Alkhalidi H, Elkhamary SM, et al. New observations regarding the retinopathy of genetically confirmed Kearns-Sayre syndrome. Retinal Cases and Brief Reports; Publish Ahead of Print. http://journals.lww.com/retinalcases/Fulltext/publishahead/NEW_OBSERVATIONS_REGARDING_THE_RETINOPATHY_OF.99068.aspx (9000).
  74. 74.
    Shamseldin HE, Alshammari M, Al-Sheddi T, Salih MA, Alkhalidi H, Kentab A, et al. Genomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes. J Med Genet. 2012;49:234–41.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Gai X, Ghezzi D, Johnson MA, Biagosch CA, Shamseldin HE, Haack TB, et al. Mutations in FBXL4, encoding a mitochondrial protein, cause early-onset mitochondrial encephalomyopathy. Am J Hum Genet. 2013;93(3):482–95.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Mercimek-Mahmutoglu S, Salomons GS. Creatine deficiency syndromes. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK3794/. Accessed 20 Feb 2017.Google Scholar
  77. 77.
    Tabarki B, Al-Hashem A, Alfadhel M. Biotin-thiamine-responsive basal ganglia disease. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK169615/. Accessed 20 Feb 2017.Google Scholar
  78. 78.
    Mohamed S, Hellani A, Elmelegy E. New mutation at BTD gene: biotidinase deficiency presenting as status epilepticus resistant to conventional anti-epileptics. Med J Cairo Univ. 2009;77:111–3.Google Scholar
  79. 79.
    Wolf B. Biotinidase deficiency. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1322/. Accessed 20 Feb 2017.Google Scholar
  80. 80.
    Carrillo N, Adams D, Venditti CP. Disorders of intracellular cobalamin metabolism. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1328/. Accessed 20 Feb 2017.Google Scholar
  81. 81.
    Gospe SM. Pyridoxine-dependent epilepsy. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1486/. Accessed 20 Feb 2017.Google Scholar
  82. 82.
    Salih MA, Kabiraj M, Gascon GG, Al Jarallah AS, Al-Zamil FA. Typical and atypical presentations of pyridoxine-dependent seizures. Saudi Med J. 1995;16(4):347–51.Google Scholar
  83. 83.
    Agadi S, Quach MM, Haneef Z. Vitamin-responsive epileptic encephalopathies in children. Epilep Res Treat. 2013;2013:510529.Google Scholar
  84. 84.
    Diekman EF, de Koning TJ, Verhoeven-Duif NM, Rovers MM, van Hasselt PM. Survival and psychomotor development with early betaine treatment in patients with severe methylenetetrahydrofolate reductase deficiency. JAMA Neurol. 2014;71:188–94.PubMedCrossRefGoogle Scholar
  85. 85.
    Munoz T, Patel J, Badilla-Porras R, Kronick J, Mercimek-Mahmutoglu S. Severe scoliosis in a patient with severe methylenetetrahydrofolate reductase deficiency. Brain Dev. 2015;37(1):168–70.PubMedCrossRefGoogle Scholar
  86. 86.
    Al-Baradie RS, Chudary MW. Diagnosis and management of cerebral folate deficiency: a form of folinic acid-responsive seizures. Neurosciences. 2014;19(4):312–6.PubMedPubMedCentralGoogle Scholar
  87. 87.
    Weiss KH. Wilson disease. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1512/. Accessed 20 Feb 2017.Google Scholar
  88. 88.
    Elmeleagy E, Mohamed S. Menkes Disease presenting with subdural fluid collection and fractures mimicking non-accidental injury. Med J Cairo Univ. 2009;77:119–21.Google Scholar
  89. 89.
    Clarke LA. Mucopolysaccharidosis type I. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1162/. Accessed 20 Feb 2017.Google Scholar
  90. 90.
    Mohamed S. Sanfilippo syndrome, glucose-6-phosphate dehydrogenase deficiency and sickle cell/β+ thalassemia in a child: the burden of consanguinity. Am J Med Genet A. 2014;164A:267–9.PubMedCrossRefGoogle Scholar
  91. 91.
    Malm D, Nilssen Ø. Alpha-mannosidosis. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1396/. Accessed 20 Feb 2017.Google Scholar
  92. 92.
    Xing M, Parker EI, Moreno-De-Luca A, Harmouche E, Terk MR. Radiological and clinical characterization of the lysosomal storage disorders: non-lipid disorders. Br J Radiol. 2014;87:1033.CrossRefGoogle Scholar
  93. 93.
    Regier DS, Tifft CJ. GLB1-related disorders. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK164500/. Accessed 20 Feb 2017.Google Scholar
  94. 94.
    Salih MA, Seidahmed MZ, El Khashab HY, Hamad MH, Bosley TM, Burn S, et al. Mutation in GM2A leads to a progressive chorea-dementia syndrome. Tremor Other Hyperkin Movem (New York, NY). 2014;5:306.Google Scholar
  95. 95.
    Salih MA. Approach to diagnosis and treatment of a child with motor unit diseases. In: Textbook of clinical pediatrics. Berlin, Heidelberg: Springer; 2012. p. 3445–55.CrossRefGoogle Scholar
  96. 96.
    Patterson M. Niemann-pick disease type C. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1296/. Accessed 20 Feb 2017.Google Scholar
  97. 97.
    Pastores GM, Hughes DA. Gaucher disease. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1269/. Accessed 20 Feb 2017.Google Scholar
  98. 98.
    Wenger DA. Krabbe disease. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1238/. Accessed 20 Feb 2017.Google Scholar
  99. 99.
    Fluharty AL. Arylsulfatase a deficiency. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1130/. Accessed 20 Feb 2017.Google Scholar
  100. 100.
    Matalon R, Michals-Matalon K. Canavan disease. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1234/. Accessed 20 Feb 2017.Google Scholar
  101. 101.
    Yang M, Cho SY, Park HD, Choi R, Kim YE, Kim J, Lee SY, Ki CS, Kim JW, Sohn YB, Song J. Clinical, biochemical and molecular characterization of Korean patients with mucolipidosis II/III and successful prenatal diagnosis. Orphan J Rare Dis. 2017;12(1):11.CrossRefGoogle Scholar
  102. 102.
    Schiffmann R, Grishchuk Y, Goldin E. Mucolipidosis IV. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1214/. Accessed 20 Feb 2017.Google Scholar
  103. 103.
    Goebel HH, Kohlschütter A, Lenard HG. Morphologic and chemical biopsy findings in mucolipidosis IV. Clin Neuropathol. 1981;1(2):73–82.Google Scholar
  104. 104.
    Mohamed S. A clinical and DNA study on patients with Neuronal ceroid lipofuscinosis in Eastern Province, Saudi Arabia. Curr Pediatr Res. 2012;16:49–52.Google Scholar
  105. 105.
    Mole SE, Williams RE. Neuronal ceroid-lipofuscinoses. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1428/. Accessed 20 Feb 2017.Google Scholar
  106. 106.
    Alazami AM, Patel N, Shamseldin HE, Anazi S, Al-Dosari MS, Alzahrani F, et al. Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families. Cell Rep. 2015;10(2):148.PubMedCrossRefGoogle Scholar
  107. 107.
    Seidahmed MZ, Salih MA, Abdulbasit OB, Samadi A, Al Hussien K, Miqdad AM, et al. Hyperekplexia, microcephaly and simplified gyral pattern caused by novel ASNS mutations, case report. BMC Neurol. 2016;16:105.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Moen MN, Fjær R, Laerdahl JK, Menchini RJ, Vigeland MD, Sheng Y, et al. Pathogenic variants in KCTD7 perturb neuronal K+ fluxes and glutamine transport. Brain. 2016;139(12):3109–20.PubMedCrossRefGoogle Scholar
  109. 109.
    Leslie N, Tinkle BT. Glycogen storage disease type II (Pompe Disease). In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1261/. Accessed 20 Feb 2017.Google Scholar
  110. 110.
    Steinberg SJ, Raymond GV, Braverman NE, Moser AB. Peroxisome biogenesis disorders, Zellweger syndrome spectrum. Peroxisome Biogenesis Disorders. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1448/. Accessed 20 Feb 2017.Google Scholar
  111. 111.
    Mohamed S, El-Meleagy E, Nasr A, Ebberink MS, Wanders RJA, Waterham HR. A mutation in PEX19 causes a severe clinical phenotype in a patient with peroxisomal biogenesis disorder. Am J Med Genet A. 2010;152A:2318–21.PubMedCrossRefGoogle Scholar
  112. 112.
    Shaheen R, Al-Dirbashi ZN, Al-Hassnan OY, Al-Owain M, Makhsheed N, Basheeri F, et al. Clinical, biochemical and molecular characterization of peroxisomal diseases in Arabs. Clin Genet. 2011;79:60–70.PubMedPubMedCentralCrossRefGoogle Scholar
  113. 113.
    Kheir AE. Zellweger syndrome: a cause of neonatal hypotonia and seizures. Sudan J Paediatr. 2011;11(2):54–8.PubMedPubMedCentralGoogle Scholar
  114. 114.
    Al-Herbish AS, Salih MAM, Al-Husain M, Al-Jurayyan NAM, Patel PJ, Palkar V. X-linked adrenoleukodystrophy in the Arab ethnic group: presentation and management of a child. Med Sci Res. 1993;21:439–41.Google Scholar
  115. 115.
    Patel PJ, Kolawole TM, Malabarey TM, Al-Herbish AS, Al-Jurrayan NA, Saleh M. Adrenoleukodystrophy: CT and MRI findings. Pediatr Radiol. 1994;25(4):256–8.CrossRefGoogle Scholar
  116. 116.
    Steinberg SJ, Moser AB, Raymond GV. X-Linked adrenoleukodystrophy. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1315/. Accessed 20 Feb 2017.Google Scholar
  117. 117.
    Kaltsas G, Kanakis G, Moser H. Adrenal insufficiency due to X-linked adrenoleukodystrophy. [Updated 2015 Feb 25]. In: De Groot LJ, Chrousos G, Dungan K, et al., editors. Endotext [Internet]. South Dartmouth, MA: MDText.com, Inc.; 2000. https://www.ncbi.nlm.nih.gov/books/NBK278944/. Accessed 21 Mar 2017.Google Scholar
  118. 118.
    Wanders RJ, Waterham HR, Leroy BP. Refsum disease. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1353/. Accessed 20 Feb 2017.Google Scholar
  119. 119.
    Al-Owain M, Mohamed S, Kaya N, Zagal A, Matthijs G, Jaeken J. A novel mutation and first report of dilated cardiomyopathy in ALG6-CDG (CDG-Ic): a case report. Orphan J Rare Dis. 2010;5:7.CrossRefGoogle Scholar
  120. 120.
    Sparks SE, Krasnewich DM. Congenital disorders of N-linked glycosylation and multiple pathway overview. Seattle: University of Washington. https://www.ncbi.nlm.nih.gov/sites/books/NBK1332/. Accessed 20 Feb 2017.
  121. 121.
    Sparks SE, Krasnewich DM. PMM2-CDG (CDG-Ia). In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1110/. Accessed 20 Feb 2017.Google Scholar
  122. 122.
    Miossec-Chauvet E, Mikaeloff Y, Heron D, Merzoug V, Cormier-Daire V, de Lonlay P, et al. Neurological presentation in pediatric patients with congenital disorders of glycosylation type Ia. Neuropediatrics. 2003;34:1–6.PubMedCrossRefGoogle Scholar
  123. 123.
    Anazi S, Maddirevula S, Faqeih E, Alsedairy H, Alzahrani F, Shamseldin HE, Patel N, Hashem M, Ibrahim N, Abdulwahab F, Ewida N. Clinical genomics expands the morbid genome of intellectual disability and offers a high diagnostic yield. Mol Psychiatry. 2017;22(4):615–24.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Alazami AM, Monies D, Meyer BF, Alzahrani F, Hashem M, Salih MA, et al. Congenital disorder of glycosylation IIa: the trouble with diagnosing a dysmorphic inborn error of metabolism. (Letter). Am J Med Genet. 2012;158A:245–6.PubMedCrossRefGoogle Scholar
  125. 125.
    Nyhan WL, O’Neill JP, Jinnah HA, Harris JC. Lesch-Nyhan syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, et al., editors. GeneReviews(®). Seattle, WA: University of Washington; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1149/. Accessed 20 Feb 2017.Google Scholar
  126. 126.
    Khneisser I, Adib S, Assaad S, Megarbane A, Karam P. Cost-benefit analysis: newborn screening for inborn errors of metabolism in Lebanon. J Med Screen. 2015;22(4):182–6.PubMedCrossRefGoogle Scholar
  127. 127.
    Elshaari FA, Sheriff DS, Agela AE, Alshaari AA, Muftah SS. Screening for inborn errors of metabolism. Int J BioMed. 2013;3(3):211–4.Google Scholar
  128. 128.
    Al-Qattan SM, Wakil SM, Anazi S, Alazami AM, Patel N, Shaheen R, Shamseldin HE, Hagos ST, AlDossari HM, Salih MA, El Khashab HY. The clinical utility of molecular karyotyping for neurocognitive phenotypes in a consanguineous population. Genet Med. 2015;17(9):719–25.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Division of Genetics/Metabolic, Department of PediatricsPrince Sultan Military Medical CityRiyadhSaudi Arabia
  2. 2.Prince Abdullah bin Khalid Celiac Disease Research Chair, Vice Deanship of Scientific Research chairsKing Saud UniversityRiyadhSaudi Arabia
  3. 3.Department of Pediatrics, College of MedicineAlFaisal UniversityRiyadhSaudi Arabia
  4. 4.Division of Pediatric Neurology, Department of PediatricsCollege of Medicine and King Khalid University Hospital, King Saud UniversityRiyadhSaudi Arabia

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