Skip to main content

Table 4 Diagnostic approach for NIHF and suspected lysosomal storage disease

From: Lysosomal storage disorder in non-immunological hydrops fetalis (NIHF) - more common than assumed? Report of four cases with transient NIHF and a review of the literature

Examination of the fetus with NIHF/ascites in utero Examination of the dead fetus with NIHF Examination of the live neonate with NIHF
   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)
  -Babygram If possible elctronmicroscopy for abnormal lysosomal shingolipid storage- NPC)
  -Photo-documentation  
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
  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
   4. Blood smear: vacuolated granulocytes and Adler granulation (GM1-gangliosidosis, Galactosialidosis, Sialidosis, ISSD, MPS VII)
  If possible electronmicroscopy  
  3. Tissue sample (unfixed) e.g. liver, spleen, heart, and muscle for histopathological and histochemical examinations.  
   5: Considering bone marrow aspiration to look for foam cells, Gaucher cells and other storage histiocytes)
  4. Placental tissue for histological analysis. Culture of this tissue is also possible (cell lines often show early senescence)  
   6. Skeletal-radiography: dysostosis multiplex, pathological fractures (ML II)
  If possible elctronmicroscopy for abnormal lysosomal shingolipid storage- NPC) Diagnosis
  5. Fetal urine (if available) for Glycosaminoglycans or Oligosaccharides  
3. Genetic analysis: amnion cells or chorion villi cells   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)
   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).
   9. EDTA-blood for DNA isolation
  1. * GAG-electrophoresis: electrophoresis of glycosaminoglycans, ** I-cell screen: lysosomal enzyme activity in serum more than 10 times the reference range. Diagnosis in fibroblasts or amnion cells: same lysosomal enzymes deficient. ***Filipin test: reaction of impaired cholesterol esterification in cultured cells with fluorescent filipin in NPC.
Back to article page

Orphanet Journal of Rare Diseases

ISSN: 1750-1172

\