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Journal of Inherited Metabolic Disease

, Volume 40, Issue 1, pp 103–112 | Cite as

Antenatal manifestations of inborn errors of metabolism: prenatal imaging findings

  • Laurent Guibaud
  • Sophie Collardeau-Frachon
  • Audrey Lacalm
  • Mona Massoud
  • Massimiliano Rossi
  • Marie Pierre Cordier
  • Christine Vianey-Saban
SSIEM 2015

Abstract

Prenatal manifestations of inborn errors of metabolism (IEM) are related to severe disorders involving metabolic pathways active in the fetal period and not compensated by maternal or placental metabolism. Some prenatal imaging findings can be suggestive of such conditions—especially in cases of consanguinity and/or recurrence of symptoms—after exclusion of the most frequent nonmetabolic etiologies. Most of these prenatal imaging findings are nonspecific. They include mainly ascites and hydrops fetalis, intrauterine growth restriction (IUGR), central nervous system (CNS) anomalies, echogenic kidneys, epiphyseal stippling, craniosynostosis, and a wide spectrum of dysostoses. These anomalies can be isolated, but in most cases, an IEM is suggested by an association of features. It must be stressed that the diagnosis of an IEM in the prenatal period is based on a close collaboration between specialists in fetal imaging, medicine, genetics, biology, and pathology.

Keywords

Craniosynostosis Cystinuria Glutaric Aciduria Type Peroxisomal Disorder Rhizomelic Chondrodysplasia Punctata 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Compliance with ethical standards

Conflict of interest

None.

Details of funding for all research studies

The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Declaration of Helsinki, 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

References

  1. Alfadhel M, Alrifai MT, Trujillano D et al (2015) Asparagine synthetase deficiency: new inborn errors of metabolism. J Inher Metab Dis Rep 22:11–16Google Scholar
  2. Amat S, Czerkiewicz I, Benoist JF et al (2011) Isolated hyperechoic fetal colon before 36 weeks’ gestation reveals cystinuria. Ultrasound Obstet Gynecol 38(5):543–547CrossRefPubMedGoogle Scholar
  3. Andersson HC, Kratz L, Kelley R (2002) Desmosterolosis presenting with multiple congenital anomalies and profound developmental delay. Am J Med Genet 113(4):315–319CrossRefPubMedGoogle Scholar
  4. Bandaralage SP, Farnaghi S, Dulhunty JM, Kothari A (2016) Antenatal and postnatal radiologic diagnosis of holocarboxylase synthetase deficiency: a systematic review. Pediatr Radiol 46(3):357–364CrossRefPubMedGoogle Scholar
  5. Bemer F, Deberg M, Schoos R et al (2015) Diagnostic pitfall in antenatal manifestations of CPT II deficiency. Clin Genet. doi: 10.1111/cge.12593 Google Scholar
  6. Boulet S, Dieterich K, Althuser M et al (2010) Brachytelephalangic chondrodysplasia punctata: prenatal diagnosis and postnatal outcome. Fetal Diagn Ther 28:186–190CrossRefPubMedGoogle Scholar
  7. Bouvier R, Maire I (1997) Diagnostic des maladies de surcharge lysosomale à révélation fœtale. Ann Pathol 17:277–280PubMedGoogle Scholar
  8. Bouvier R, Cordier MP, Loget P et al (2008) Maladies métaboliques. In: Ouvrage collectif de la Société Française de Fetopathologie (ed) Pathologie fœtale et placentaire pratique. Sauramps, Montpellier, pp 465–484Google Scholar
  9. Brasseur-Daudruy M, Garel C, Brossard V et al (2006) Hyper-echogenic colon: a prenatal sign of cystinuria? Prenat Diagn 26:1254–1255CrossRefPubMedGoogle Scholar
  10. Brassier A, Ottolenghi C, Boddaert N (2012) Prenatal symptoms and diagnosis of inherited metabolic diseases. Arch Pediatr 19:959–969Google Scholar
  11. Cañueto J, Girós M, Ciria S et al (2012) Clinical, molecular and biochemical characterization of nine Spanish families with Conradi-Hünermann-Happle syndrome: new insights into CDPX2 with a comprehensive review of literature. Br J Dermatol 166:830–838CrossRefPubMedGoogle Scholar
  12. Carmi-Nawi N, Malinger G, Mandel H et al (2011) Prenatal brain disruption in molybdenum cofactor deficiency. J Child Neurol 26:460–464CrossRefPubMedGoogle Scholar
  13. Chaumoitre K, Brun M, Cassart M et al (2006) Differential diagnosis of fetal hyperechogenic cystic kidneys unrelated to renal tract anomalies: a multicenter study. Ultrasound Obstet Gynecol 28:911–917CrossRefPubMedGoogle Scholar
  14. Chisholm CA, Vavelidis F, Lovell MA et al (2001) Prenatal diagnosis of multiple acyl-CoA dehydrogenase deficiency: association with elevated a-fetoprotein and cystic renal changes. Prenat Diagn 21(10):856–859CrossRefPubMedGoogle Scholar
  15. de Koning TJ (2013) Amino acid synthesis deficiencies. Handb Clin Neurol 113:1775–1783CrossRefPubMedGoogle Scholar
  16. de Koning TJ, Duran M, Van Maldergem L et al (2002) Congenital microcephaly and seizures due to 3-phosphoglycerate dehydrogenase deficiency: outcome of treatment with amino acids. J Inherit Metab Dis 25:119–125CrossRefPubMedGoogle Scholar
  17. Decramer S, Parant O, Beaufils S et al (2007) Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys. J Am Soc Nephrol 18(3):923–933CrossRefPubMedGoogle Scholar
  18. Elpeleg ON, Hammerman C, Saada A et al (2001) Antenatal presentation of carnitine palmitoyltransferase II deficiency. Am J Med Genet 102(2):183–187CrossRefPubMedGoogle Scholar
  19. Filges I, Kang A, Hench J et al (2011) Fetal polydactyly: a study of 24 cases ascertained by prenatal sonography. J Ultrasound Med 30(7):1021–1029PubMedGoogle Scholar
  20. Froissart R, Cheillan D, Bouvier R et al (2005) Clinical, morphological, and molecular aspects of sialic acid storage disease manifesting in utero. J Med Genet 42:829–836CrossRefPubMedPubMedCentralGoogle Scholar
  21. Fung AS, Wilson S, Toi A (1992) Echogenic colonic meconium in the third trimester: a normal sonographic finding. J Ultrasound Med 11(12):676–678Google Scholar
  22. Giese A, Kirschner-Schwabe R, Blumchen K et al (2007) Prenatal manifestation of pancytopenia in Pearson marrow-pancreas syndrome caused by a mitochondrial DNA deletion. Am J Med Genet A 143A(3):285–288CrossRefPubMedGoogle Scholar
  23. Gimovsky AC, Luzi P, Berghella V (2015) Lysosomal storage disease as an etiology of nonimmune hydrops. Am J Obstet Gynecol 212:281–290CrossRefPubMedGoogle Scholar
  24. Goldenberg A, Wolf C, Chevy F et al (2004) Antenatal manifestations of Smith-Lemli-Opitz (RSH) syndrome: a retrospective survey of 30 cases. Am J Med Genet A 124A:423–436CrossRefPubMedGoogle Scholar
  25. Häberle J, Görg B, Rutsch F et al (2005) Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med 353:1926–1933CrossRefPubMedGoogle Scholar
  26. Hertz-Pannier L, Déchaux M, Sinico M et al (2006) Congenital disorders of glycosylation type I: a rare but new cause of hyperechoic kidneys in infants and children due to early microcystic changes. Pediatr Radiol 36(2):108–114CrossRefPubMedGoogle Scholar
  27. Irving MD, Chitty LS, Mansour S, Hall CM (2008) Chondrodysplasia punctata: a clinical diagnostic and radiological review. Clin Dysmorphol 17:229–241CrossRefPubMedGoogle Scholar
  28. Ketwaroo PD, Robson CD, Estroff JA (2015) Prenatal imaging of craniosynostosis syndromes. Semin Ultrasound CT MRI 36:453–464CrossRefGoogle Scholar
  29. Konstantinidou A, Karadimas C, Waterham HR et al (2008) Pathologic, radiographic and molecular findings in three fetuses diagnosed with HEM/Greenberg skeletal dysplasia. Prenat Diagn 28:309–312CrossRefPubMedGoogle Scholar
  30. L’herminé-Coulomb A, Beuzen F, Bouvier R et al (2005) Fetal type IV glycogen storage disease: clinical, enzymatic, and genetic data of a pure muscular form with variable and early antenatal manifestations in the same family. Am J Med Genet A 139A:118–222CrossRefPubMedGoogle Scholar
  31. Lacalm A, Nadaud B, Massoud M et al (2016) Prenatal diagnosis of cobblestone lissencephaly associated with Walker-Warburg syndrome based on a specific sonographic pattern. Ultrasound Obstet Gynecol 47(1):117–122CrossRefPubMedGoogle Scholar
  32. Lee RW, Yoshida S, Jung ES, Mori S, Baker EH, Porter FD (2013) Corpus callosum measurements correlate with developmental delay in Smith-Lemli-Opitz syndrome. Pediatr Neurol 49(2):107–112CrossRefPubMedPubMedCentralGoogle Scholar
  33. Lefebvre M, Dufernez F, Bruel AL et al (2015) Severe X-linked chondrodysplasia punctata in nine new female fetuses. Prenat Diagn 35:675–684CrossRefPubMedGoogle Scholar
  34. Lepais L, Cheillan D, Collardeau-Frachon S et al (2015) ALG3-CDG: report of two siblings with antenatal features carrying homozygous p.Gly96Arg mutation. Am J Med Genet A 167:2748–2754CrossRefGoogle Scholar
  35. Léticée N, Bessières-Grattagliano B, Dupré T et al (2010) Should PMM2-deficiency (CDG Ia) be searched in every case of unexplained hydrops fetalis? Mol Gent Metab 101:253–277CrossRefGoogle Scholar
  36. Mellerio C, Marignier S, Roth P et al (2008) Prenatal cerebral ultrasound and MRI findings in glutaric aciduria Type 1: a de novo case. Ultrasound Obstet Gynecol 31:712–714CrossRefPubMedGoogle Scholar
  37. Mochel F, Grébille AG, Benachi A et al (2006) Contribution of fetal MR imaging in the prenatal diagnosis of Zellweger syndrome. Am J Neuroradiol 27:333–336PubMedGoogle Scholar
  38. Moreno CA, Kanazawa T, Barini R et al (2013) Non-immune hydrops fetalis: a prospective study of 53 cases. Am J Med Genet A 161A(12):3078–3086CrossRefPubMedGoogle Scholar
  39. Offiah AC, Mansour S, Jeffrey I et al (2003) Greenberg dysplasia (HEM) and lethal X linked dominant Conradi-Hünermann chondrodysplasia punctata (CDPX2): presentation of two cases with overlapping phenotype. J Med Genet 40:e129CrossRefPubMedPubMedCentralGoogle Scholar
  40. Oldani E, Garel C, Bucourt M, Carbillon L (2015) Prenatal diagnosis of Antley-Bixler syndrome and POR deficiency. Am J Case Rep 16:882–885PubMedPubMedCentralGoogle Scholar
  41. Patel KP, O’Brien TW, Subramony SH et al (2012) The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab 105:34–43CrossRefPubMedGoogle Scholar
  42. Paupe A, Bidat L, Sonigo P et al (2002) Prenatal diagnosis of hypoplasia of the corpus callosum in association with nonketotic hyperglycinemia. Ultrasound Obstet Gynecol 20:616–619CrossRefPubMedGoogle Scholar
  43. Pettazzoni, M, Streichenberger N, Mezin P et al (2015) Congenital and perinatal glycogen storage disease type IV: clinical, pathological and biological data in 5 cases. J Inher Metab Dis 38(Suppl.1):S182Google Scholar
  44. Poll-The BT, Gärtner J (2012) Clinical diagnosis, biochemical findings and MRI spectrum of peroxisomal disorders. Biochim Biophys Acta 1822:1421–1429CrossRefPubMedGoogle Scholar
  45. Prick BW, Hop WC, Duvekot JJ (2012) Maternal phenylketonuria and hyperphenylalaninemia in pregnancy: pregnancy complications and neonatal sequele in untreated and treated pregnancies. Am J Clin Nutr 95:374–382CrossRefPubMedGoogle Scholar
  46. Rigaud C, Lebre AS, Touraine R et al (2013) Natural history of Barth syndrome: a national cohort study of 22 patients. Orphanet J Rare Dis 8:70–82CrossRefPubMedPubMedCentralGoogle Scholar
  47. Rossi M, Hall CM, Bouvier R et al (2015) Radiographic features of the skeleton in disorders of post-squalene cholesterol biosynthesis. Pediatr Radiol 45:965–976CrossRefPubMedGoogle Scholar
  48. Roume J, Ville Y (2004) Prenatal diagnosis of genetic renal diseases: breaking the code. Ultrasound Obstet Gynecol 24(1):10–18CrossRefPubMedGoogle Scholar
  49. Saudubray JM (2011) Clinical approach to inborn errors of metabolism. In: Saudubray JM, van den Berghe G, Walter J (eds) Inborn metabolic diseases. Springer, Berlin, pp 3–52Google Scholar
  50. Spiegel R, Raas-Rothschild A, Reish O et al (2009) The clinical spectrum of fetal Niemann-Pick type C. Am J Med Genet 149A:446–450CrossRefPubMedGoogle Scholar
  51. Steward CG, Newbury-Ecob RA, Hastings R et al (2010) Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth. Prenat Diagn 30:970–976CrossRefPubMedPubMedCentralGoogle Scholar
  52. Tavares MV, Santos MJ, Domingues AP et al (2013) Antenatal manifestations of mitochondrial disorders. J Inherit Metab Dis 36:805–811CrossRefPubMedGoogle Scholar
  53. Valayannopoulos V, Verheven NM, Mention K et al (2006) Transaldolase deficiency: a new cause of hydrops fetalis and neonatal multi-organ disease. J Pediatr 149:713–717CrossRefPubMedGoogle Scholar
  54. Vianey-Saban C, Bouvier R, Cochat P et al (2000) Antenatal expression of multiple acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis 23:345–348CrossRefPubMedGoogle Scholar
  55. von Kleist-Retzow JC, Cormier-Daire V, Viot G et al (2003) Antenatal manifestations of mitochondrial respiratory chain deficiency. J Pediatr 143:208–212CrossRefGoogle Scholar
  56. Waterham HR, Ferdinandusse S, Wanders RJ (2016) Human disorders of peroxisome metabolism and biogenesis. Biochim Biophys Acta 1863:922–933CrossRefPubMedGoogle Scholar
  57. Wopereis S, Lefeber D, Morava E, Wevers R (2006) Mechanisms in protein O-glycan biosynthesis and clinical and molecular aspects of protein O-glycan biosynthesis: a review. Clin Chem 52:574--600Google Scholar
  58. Zolotushko J, Flusser H, Markus B et al (2011) The desmosterolosis phenotype: spasticity, microcephaly and micrognathia with agenesis of corpus callosum and loss of white matter. Eur J Hum Genet 19:942–946CrossRefPubMedPubMedCentralGoogle Scholar
  59. Zwijnenburg PJ, Deurloo KL, Waterham HR et al (2010) Second trimester prenatal diagnosis of rhizomelic chondrodysplasia punctata type 1 on ultrasound findings. Prenat Diagn 30(2):162–164CrossRefPubMedGoogle Scholar

Copyright information

© SSIEM 2016

Authors and Affiliations

  • Laurent Guibaud
    • 1
    • 2
    • 3
  • Sophie Collardeau-Frachon
    • 4
  • Audrey Lacalm
    • 1
  • Mona Massoud
    • 2
  • Massimiliano Rossi
    • 5
  • Marie Pierre Cordier
    • 5
  • Christine Vianey-Saban
    • 6
  1. 1.Département d’Imagerie Pédiatrique et FœtaleHôpital Femme Mère EnfantLyon BronFrance
  2. 2.Centre Pluridisciplinaire de Diagnostic PrénatalHôpital Femme Mère EnfantLyon BronFrance
  3. 3.Université Claude Bernard Lyon I, Imagerie Pédiatrique et Fœtale, Hôpital Femme Mère EnfantLyon-BronFrance
  4. 4.Département de PathologieGroupement Hospitalier EstLyon BronFrance
  5. 5.Service de Génétique, Centre de Référence des Anomalies de DéveloppementHôpital Femme Mère EnfantLyon BronFrance
  6. 6.Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et PathologieGroupement Hospitalier EstLyon BronFrance

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