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Antenatal manifestations of inborn errors of metabolism: biological diagnosis

  • SSIEM 2015
  • Published:
Journal of Inherited Metabolic Disease

Abstract

Inborn errors of metabolism (IEMs) that present with abnormal imaging findings in the second half of pregnancy are mainly lysosomal storage disorders (LSDs), cholesterol synthesis disorders (CSDs), glycogen storage disorder type IV (GSD IV), peroxisomal disorders, mitochondrial fatty acid oxidation defects (FAODs), organic acidurias, aminoacidopathies, congenital disorders of glycosylation (CDGs), and transaldolase deficiency. Their biological investigation requires fetal material. The supernatant of amniotic fluid (AF) is useful for the analysis of mucopolysaccharides, oligosaccharides, sialic acid, lysosphingolipids and some enzyme activities for LSDs, 7- and 8-dehydrocholesterol, desmosterol and lathosterol for CSDs, acylcarnitines for FAODs, organic acids for organic acidurias, and polyols for transaldolase deficiency. Cultured AF or fetal cells allow the measurement of enzyme activities for most IEMs, whole-cell assays, or metabolite measurements. The cultured cells or tissue samples taken after fetal death can be used for metabolic profiling, enzyme activities, and DNA extraction. Fetal blood can also be helpful. The identification of vacuolated cells orients toward an LSD, and plasma is useful for diagnosing peroxisomal disorders, FAODs, CSDs, some LSDs, and possibly CDGs and aminoacidopathies. We investigated AF of 1700 pregnancies after exclusion of frequent etiologies of nonimmune hydrops fetalis and identified 108 fetuses affected with LSDs (6.3 %), 29 of them with mucopolysaccharidosis type VII (MPS VII), and six with GSD IV (0.3 %). In the AF of 873 pregnancies, investigated because of intrauterine growth restriction and/or abnormal genitalia, we diagnosed 32 fetuses affected with Smith-Lemli-Opitz syndrome (3.7 %).

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Authors and Affiliations

  1. Service Maladies Héréditaires du Métabolisme et Dépistage Néonatal, Centre de Biologie et de Pathologie Est CHU de Lyon, Lyon, France

    Christine Vianey-Saban, Cécile Acquaviva, David Cheillan, Cécile Pagan, Magali Pettazzoni, Monique Piraud & Roseline Froissart

  2. Unité INSERM U1060 CarMeN Laboratory, University Lyon-1, Lyon, France

    Christine Vianey-Saban, David Cheillan & Sophie Collardeau-Frachon

  3. UMR 5305 CNRS/UCBL, Lyon, France

    Cécile Acquaviva & Roseline Froissart

  4. Département de Pathologie, Centre de Biologie et de Pathologie Est CHU de Lyon, Lyon, France

    Sophie Collardeau-Frachon

  5. Département d’Imagerie Pédiatrique et Fœtale, Hôpital Femme Mère Enfant CHU de Lyon, Lyon, France

    Laurent Guibaud

  6. Lyon Neuroscience Research Center, CNRS UMR5292; INSERM U1028, Université Claude Bernard Lyon 1, Lyon, France

    Cécile Pagan

  7. Département PM2, Plateforme de Métabolomique, Peptidomique et dosage de Médicaments, APHP, Hôpital Saint Antoine, Paris, France, Laboratoire de spectrométrie de masse, INSERM ERL 1157, CNRS UMR 7203 LBM, Sorbonne Universités–UPMC, Paris, France

    Antonin Lamazière

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  1. Christine Vianey-Saban
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Vianey-Saban, C., Acquaviva, C., Cheillan, D. et al. Antenatal manifestations of inborn errors of metabolism: biological diagnosis. J Inherit Metab Dis 39, 611–624 (2016). https://doi.org/10.1007/s10545-016-9947-8

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