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 %).