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Antenatal manifestations of inborn errors of metabolism: prenatal imaging findings

  • SSIEM 2015
  • Published:
Journal of Inherited Metabolic Disease

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.

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References

  • Alfadhel M, Alrifai MT, Trujillano D et al (2015) Asparagine synthetase deficiency: new inborn errors of metabolism. J Inher Metab Dis Rep 22:11–16

    Google Scholar 

  • Amat S, Czerkiewicz I, Benoist JF et al (2011) Isolated hyperechoic fetal colon before 36 weeks’ gestation reveals cystinuria. Ultrasound Obstet Gynecol 38(5):543–547

    Article  CAS  PubMed  Google Scholar 

  • Andersson HC, Kratz L, Kelley R (2002) Desmosterolosis presenting with multiple congenital anomalies and profound developmental delay. Am J Med Genet 113(4):315–319

    Article  PubMed  Google Scholar 

  • 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):357–364

    Article  PubMed  Google Scholar 

  • 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 

  • Boulet S, Dieterich K, Althuser M et al (2010) Brachytelephalangic chondrodysplasia punctata: prenatal diagnosis and postnatal outcome. Fetal Diagn Ther 28:186–190

    Article  CAS  PubMed  Google Scholar 

  • Bouvier R, Maire I (1997) Diagnostic des maladies de surcharge lysosomale à révélation fœtale. Ann Pathol 17:277–280

    CAS  PubMed  Google Scholar 

  • 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 465–484

    Google Scholar 

  • Brasseur-Daudruy M, Garel C, Brossard V et al (2006) Hyper-echogenic colon: a prenatal sign of cystinuria? Prenat Diagn 26:1254–1255

    Article  CAS  PubMed  Google Scholar 

  • Brassier A, Ottolenghi C, Boddaert N (2012) Prenatal symptoms and diagnosis of inherited metabolic diseases. Arch Pediatr 19:959–969

  • 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 166:830–838

    Article  PubMed  Google Scholar 

  • Carmi-Nawi N, Malinger G, Mandel H et al (2011) Prenatal brain disruption in molybdenum cofactor deficiency. J Child Neurol 26:460–464

    Article  PubMed  Google Scholar 

  • 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 28:911–917

    Article  CAS  PubMed  Google Scholar 

  • 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):856–859

    Article  CAS  PubMed  Google Scholar 

  • de Koning TJ (2013) Amino acid synthesis deficiencies. Handb Clin Neurol 113:1775–1783

    Article  PubMed  Google Scholar 

  • 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 25:119–125

    Article  PubMed  Google Scholar 

  • 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):923–933

    Article  CAS  PubMed  Google Scholar 

  • Elpeleg ON, Hammerman C, Saada A et al (2001) Antenatal presentation of carnitine palmitoyltransferase II deficiency. Am J Med Genet 102(2):183–187

    Article  CAS  PubMed  Google Scholar 

  • 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):1021–1029

    PubMed  Google Scholar 

  • 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 42:829–836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fung AS, Wilson S, Toi A (1992) Echogenic colonic meconium in the third trimester: a normal sonographic finding. J Ultrasound Med 11(12):676–678

  • 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):285–288

    Article  CAS  PubMed  Google Scholar 

  • Gimovsky AC, Luzi P, Berghella V (2015) Lysosomal storage disease as an etiology of nonimmune hydrops. Am J Obstet Gynecol 212:281–290

    Article  PubMed  Google Scholar 

  • 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:423–436

    Article  PubMed  Google Scholar 

  • Häberle J, Görg B, Rutsch F et al (2005) Congenital glutamine deficiency with glutamine synthetase mutations. N Engl J Med 353:1926–1933

    Article  PubMed  Google Scholar 

  • 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):108–114

    Article  PubMed  Google Scholar 

  • Irving MD, Chitty LS, Mansour S, Hall CM (2008) Chondrodysplasia punctata: a clinical diagnostic and radiological review. Clin Dysmorphol 17:229–241

    Article  PubMed  Google Scholar 

  • Ketwaroo PD, Robson CD, Estroff JA (2015) Prenatal imaging of craniosynostosis syndromes. Semin Ultrasound CT MRI 36:453–464

    Article  Google Scholar 

  • 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 28:309–312

    Article  CAS  PubMed  Google Scholar 

  • 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:118–222

    Article  PubMed  Google Scholar 

  • 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):117–122

    Article  CAS  PubMed  Google Scholar 

  • 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):107–112

    Article  PubMed  PubMed Central  Google Scholar 

  • Lefebvre M, Dufernez F, Bruel AL et al (2015) Severe X-linked chondrodysplasia punctata in nine new female fetuses. Prenat Diagn 35:675–684

    Article  CAS  PubMed  Google Scholar 

  • 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 167:2748–2754

    Article  CAS  Google Scholar 

  • 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 101:253–277

    Article  Google Scholar 

  • 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 31:712–714

    Article  CAS  PubMed  Google Scholar 

  • Mochel F, Grébille AG, Benachi A et al (2006) Contribution of fetal MR imaging in the prenatal diagnosis of Zellweger syndrome. Am J Neuroradiol 27:333–336

    CAS  PubMed  Google Scholar 

  • 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):3078–3086

    Article  PubMed  Google Scholar 

  • 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:e129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oldani E, Garel C, Bucourt M, Carbillon L (2015) Prenatal diagnosis of Antley-Bixler syndrome and POR deficiency. Am J Case Rep 16:882–885

    PubMed  PubMed Central  Google Scholar 

  • 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 105:34–43

    Article  CAS  PubMed  Google Scholar 

  • 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 20:616–619

    Article  CAS  PubMed  Google Scholar 

  • 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):S182

  • Poll-The BT, Gärtner J (2012) Clinical diagnosis, biochemical findings and MRI spectrum of peroxisomal disorders. Biochim Biophys Acta 1822:1421–1429

    Article  CAS  PubMed  Google Scholar 

  • 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 95:374–382

    Article  CAS  PubMed  Google Scholar 

  • 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 8:70–82

    Article  PubMed  PubMed Central  Google Scholar 

  • Rossi M, Hall CM, Bouvier R et al (2015) Radiographic features of the skeleton in disorders of post-squalene cholesterol biosynthesis. Pediatr Radiol 45:965–976

    Article  PubMed  Google Scholar 

  • Roume J, Ville Y (2004) Prenatal diagnosis of genetic renal diseases: breaking the code. Ultrasound Obstet Gynecol 24(1):10–18

    Article  CAS  PubMed  Google Scholar 

  • 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 3–52

    Google Scholar 

  • Spiegel R, Raas-Rothschild A, Reish O et al (2009) The clinical spectrum of fetal Niemann-Pick type C. Am J Med Genet 149A:446–450

    Article  CAS  PubMed  Google Scholar 

  • Steward CG, Newbury-Ecob RA, Hastings R et al (2010) Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth. Prenat Diagn 30:970–976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tavares MV, Santos MJ, Domingues AP et al (2013) Antenatal manifestations of mitochondrial disorders. J Inherit Metab Dis 36:805–811

    Article  CAS  PubMed  Google Scholar 

  • Valayannopoulos V, Verheven NM, Mention K et al (2006) Transaldolase deficiency: a new cause of hydrops fetalis and neonatal multi-organ disease. J Pediatr 149:713–717

    Article  PubMed  Google Scholar 

  • Vianey-Saban C, Bouvier R, Cochat P et al (2000) Antenatal expression of multiple acyl-CoA dehydrogenase deficiency. J Inherit Metab Dis 23:345–348

    Article  CAS  PubMed  Google Scholar 

  • von Kleist-Retzow JC, Cormier-Daire V, Viot G et al (2003) Antenatal manifestations of mitochondrial respiratory chain deficiency. J Pediatr 143:208–212

    Article  Google Scholar 

  • Waterham HR, Ferdinandusse S, Wanders RJ (2016) Human disorders of peroxisome metabolism and biogenesis. Biochim Biophys Acta 1863:922–933

    Article  CAS  PubMed  Google Scholar 

  • 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--600

  • 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 19:942–946

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):162–164

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Département d’Imagerie Pédiatrique et Fœtale, Hôpital Femme Mère Enfant, Lyon Bron, France

    Laurent Guibaud & Audrey Lacalm

  2. Centre Pluridisciplinaire de Diagnostic Prénatal, Hôpital Femme Mère Enfant, Lyon Bron, France

    Laurent Guibaud & Mona Massoud

  3. Université Claude Bernard Lyon I, Imagerie Pédiatrique et Fœtale, Hôpital Femme Mère Enfant, 59, Boulevard Pinel, 69677, Lyon-Bron, France

    Laurent Guibaud

  4. Département de Pathologie, Groupement Hospitalier Est, Lyon Bron, France

    Sophie Collardeau-Frachon

  5. Service de Génétique, Centre de Référence des Anomalies de Développement, Hôpital Femme Mère Enfant, Lyon Bron, France

    Massimiliano Rossi & Marie Pierre Cordier

  6. Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et Pathologie, Groupement Hospitalier Est, Lyon Bron, France

    Christine Vianey-Saban

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  1. Laurent Guibaud
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  2. Sophie Collardeau-Frachon
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  3. Audrey Lacalm
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  4. Mona Massoud
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  7. Christine Vianey-Saban
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Correspondence to Laurent Guibaud.

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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.

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Communicated by: Jaak Jaeken

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Guibaud, L., Collardeau-Frachon, S., Lacalm, A. et al. Antenatal manifestations of inborn errors of metabolism: prenatal imaging findings. J Inherit Metab Dis 40, 103–112 (2017). https://doi.org/10.1007/s10545-016-9992-3

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  • DOI: https://doi.org/10.1007/s10545-016-9992-3

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