Table 4 Diagnostic approach for NIHF and suspected lysosomal storage disease
Examination of the fetus with NIHF/ascites in utero | Examination of the dead fetus with NIHF | Examination of the live neonate with NIHF |
|---|---|---|
| Â | Â | Screening |
1. Amniotic fluid GAG-electrophoresis*, lysosomal enzymes elevated in ML II | 1.Postnatal autopsy should be discussed in every individual fetus | 1. Placental tissue for histological analysis. Culture of this tissue is also possible (cell lines often show early senescence) |
| Â | -Babygram | If possible elctronmicroscopy for abnormal lysosomal shingolipid storage- NPC) |
| Â | -Photo-documentation | Â |
2. Amnion cells/Chorionic villi: enzyme measurements of ß-Glucocerebrosidase (Gaucher disease), N-Acetyl-Glukosamin-6-Sulfatsulfatase (MPS IVA), ß-Glucoronidase (MPS VII), Neuraminidase and ß-Galactosidase (Galactosialidosis, GM1 Gangliosidosis and Sialidosis). Ceramidase (Farber disease), Acid lipase (Wolman disease), Sphingomyelinase (NPA) |  | 2. Urine for oligosaccharides and GAG-electrophoresis |
| Â | 2. Skin biopsy: DNA isolation for genetics and cultivated cells for biochemical tests (enzyme analysis) | 3. Screening test in Plasma/Serum: I-cell screen**, chitotriosidase |
| Â | Â | 4. Blood smear: vacuolated granulocytes and Adler granulation (GM1-gangliosidosis, Galactosialidosis, Sialidosis, ISSD, MPS VII) |
| Â | If possible electronmicroscopy | Â |
| Â | 3. Tissue sample (unfixed) e.g. liver, spleen, heart, and muscle for histopathological and histochemical examinations. | Â |
| Â | Â | 5: Considering bone marrow aspiration to look for foam cells, Gaucher cells and other storage histiocytes) |
| Â | 4. Placental tissue for histological analysis. Culture of this tissue is also possible (cell lines often show early senescence) | Â |
| Â | Â | 6. Skeletal-radiography: dysostosis multiplex, pathological fractures (ML II) |
| Â | If possible elctronmicroscopy for abnormal lysosomal shingolipid storage- NPC) | Diagnosis |
| Â | 5. Fetal urine (if available) for Glycosaminoglycans or Oligosaccharides | Â |
3. Genetic analysis: amnion cells or chorion villi cells | Â | 7. Skin biopsy: (best with eccrine glands) DNA isolation for genetics and cultivated cells for biochemical tests (enzyme analysis), Filipin test*** for NPC, abnormal lysosomal free sialic acid storage (ISSD) |
| Â | Â | If possible electronmicroscopy |
|  |  | 8. Leucocytes and plasma (also possible in fibroblasts): measuring lysosomal enzymes of ß-Glucocerebrosidase (Gaucher), N-Acetyl-Glukosamin-6-Sulfatsulfatase (MPS IVA), ß-Glucoronidase (MPS VII), Neuraminidase and ß-Galactosidase (Galactosialidosis, GM1 Gangliosidosis and Sialidosis) Ceramidase (Farber disease). Acid lipase (Wolman disease), Sphingomyelinase (NPA). |
| Â | Â | 9. EDTA-blood for DNA isolation |