ABSTRACT
BACKGROUND: At least 20 inborn errors of metabolism may cause hydrops fetalis. Most of these are lysosomal storage diseases. The study proposes a diagnostic flowchart for prenatal diagnosis of non-immune hydrops fetalis. METHODS: This study contains a series of 75 non-immune hydrops fetalis pregnancies. Mucopolysaccharides, oligosaccharides, neuraminic acid and 21 lysosomal enzymes were measured in amniotic fluid and cultured amniotic cells. RESULTS: The study gives reference values for mucopolysaccharides and neuraminic acid at various stages of gestation. Four definite and two probable lysosomal diagnoses were found among the 75 investigated cases (=5.3-8%). Fetal death was found to cause false positive values for mucopolysaccharides in amniotic fluid. In the galactosialidosis case, two novel mutations were found in the cathepsin A gene. CONCLUSIONS: Reference values for mucopolysaccharides and neuraminic acid depend on gestational age. In a relatively high percentage of the hydrops foetalis pregnancies, a lysosomal aetiology is found. This study provides a strategy to diagnose lysosomal diseases in hydrops fetalis pregnancies. Awareness of lysosomal storage diseases causing hydrops fetalis is useful as it gives an opportunity for risk evaluation, genetic counseling to parents and targeted prenatal diagnostics for ensuing pregnancies.
Subject(s)
Gestational Age , Hydrops Fetalis/diagnosis , Lysosomal Storage Diseases/diagnosis , Prenatal Diagnosis/methods , Amniotic Fluid/chemistry , Cathepsin A/genetics , Cells, Cultured , Female , Glycosaminoglycans/analysis , Humans , Hydrops Fetalis/genetics , Hydrops Fetalis/mortality , Hydrops Fetalis/physiopathology , Lysosomal Storage Diseases/etiology , Lysosomal Storage Diseases/genetics , Lysosomal Storage Diseases/mortality , Lysosomes/enzymology , Mutation , N-Acetylneuraminic Acid/analysis , Oligosaccharides/analysis , Pregnancy , Reference Values , Risk Factors , Sialoglycoproteins/genetics , Sialoglycoproteins/metabolismABSTRACT
BACKGROUND: There is no comprehensive analytical technique to analyze N-acetylated metabolites in urine. Many of these compounds are involved in inborn errors of metabolism. In the present study, we examined the potential of proton nuclear magnetic resonance ((1)H-NMR) spectroscopy as a tool to identify and quantify N-acetylated metabolites in urine of patients with various inborn errors of metabolism. METHODS: We performed (1)H-NMR spectroscopy on a 500 MHz spectrometer. Using a combination of one- and two-dimensional correlation spectroscopy (COSY) (1)H-NMR spectra, we were able to assign and quantify resonances of characteristic N-acetylated compounds products in urine of patients with 13 inborn errors of metabolism. RESULTS: The disease-specific N-acetylated metabolites were excreted at concentrations >100 micromol/mmol of creatinine in the patients' urine. In control urine samples, the concentration of individual N-acetyl-containing compounds was <40 micromol/mmol of creatinine. The combination of one- and two-dimensional COSY NMR spectroscopy led to the correct diagnosis of nine different inborn errors of metabolism. No abnormalities were observed in the spectra of urine from patients with G(M1)- or G(M2)-gangliosidosis. We also determined the (1)H-NMR characteristics of N-acetylated metabolites that may be relevant to human metabolism. CONCLUSION: (1)H-NMR spectroscopy may be used to identify and quantify N-acetylated metabolites of diagnostic importance for the field of inborn errors of metabolism.
