Prenatal Niemann-Pick Disease: Biochemical and Histologic Examination of a 19-Gestational Week Fetus

Abstract

Prenatal diagnosis of Niemann-Pick disease was confirmed by deficiency of sphingomyelinase activity and increase in sphingomyelin content in the liver of an affected fetus. Morphologic findings included cellular enlargement with cytoplasmic vacuolization and eccentric nuclei on light microscopy, increased deposition of phospholipids demonstrated by lipid histochemistry, and increased acid phosphatase activity by enzyme histochemistry. When visualized under electron microscopy, lipid cytosomes characteristic of the sphingolipid storage diseases were seen in hepatocytes, splenic cells, the endothelium and pericytes of cerebral vessels as well as in occasional neurons. Sphingolipid accumulation and morphologic findings indicate that biochemical and pathologic manifestations are well advanced in organs destined to produce the earliest clinical signs. Speculation Early pathologic manifestations observed in a 19-gestational week fetus suggest that any peri-or postnatal therapy devised for Niemann-Pick disease, Type A is likely to be ineffective unless it can reverse the already existing central nervous system damage.

Ocular ultrastructural study in a fetus with type II glycogenosis.

“…Although no ocular abnormalities except strabismus (Smith and Reinecke, 1972) have been reported clinically, the eyes are markedly involved in type II glycogenosis. Toussaint and Danis (1965) demonstrated on necropsy material the accumulation of glycogen in the mural cells of the retinal capillaries, Fig.…”

“…x 16 000) and resulted in the therapeutic abortion of a fetus with type II glycogenosis. This biochemical technique is now widely used for the prenatal diagnosis of lysosomal diseases and allowed histopathological and biochemical analysis of affected fetal tissues (Adachi et al, 1974;Schneider et al, 1972), including the eyes (Howes et al, 1975). In our case these investigations indicated the early lysosomal storage of glycogen in skeletal muscles, liver, Schwann cells of peripheral nerves, skin, kidney, and to a much less extent in heart and central nervous system, strictly paralleling, although at a much earlier age, our previous findings in the affected sibling thought to represent a childhood phenotype rather than a classical example of Pompe disease (Martin et al, 1976).…”

“…Toussaint and Danis (1965) observed by light microscopy the widespread storage of glycogen in the eyes of an infant with Pompe disease. Ultrastructural changes of the ocular muscles have been studied by Smith and Reinecke (1972), but the ocular lesions have not, to our knowledge, been reported by electron microscopy.…”

Chemical and biochemical studies in fetuses affected with nieman‐pick disease type A

“…Deficiency of sphingomyelinase, an enzyme which catalyses cleavage of phosphatidylcholine from sphingomyelin, has been demonstrated in patients with two types, A and B, of this disorder (Frederickson and Sloan, 1972;Brady et al, 1966;Schneider and Kennedy, 1967). Due to the feasibility of sphingomyelinase-activity determinations in amniotic fluid cell cultures the prenatal diagnosis of the lethal, infantile neuronopathic form, Niemann-Pick disease type A, is at present possible (Chazan et al, 1978;Epstein et al, 1971 ;Schneider et al, 1972).…”

Neonatal chitotriosidase activity is not predictive for Niemann–Pick disease type A/B: Implications for newborn screening for lysosomal storage disorders

“…Actually, neonatal assessment of Ch activity is hypothetically instrumental for reducing false-positive and -negative results for specific disorders, such as Niemann-Pick disease. The rationale of this potential lies in the pathophysiology of this disease, with sphingomyelin storage occurring since fetal life [7].…”