July 1, 1998

Electron Microscopy in a Child with Seizures

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Clinical History
Light and Electron Microscopy
Diagnosis & Discussion
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Diagnosis:

Neuronal ceroid lipofuscinosis, late infantile type

Discussion:

The neuronal ceroid lipofuscinoses are a group of progressive encephalopathies which are inherited in an autosomal recessive manner. Four main types are recognized: infantile, late infantile, juvenile and adult.

Morphologically they are characterized by widespread accumulation of autofluorescent lipopigments inside and outside the central nervous system. In the infantile type the lipopigments are granular. The late infantile type shows characteristic curvilinear profiles. Fingerprint profiles are seen in the classical juvenile type while the adult type can be somewhat variable showing granular material and/or fingerprint profiles. Many cell types contain the abnormal inclusions including endothelial cells and amniotic fluid cells. This has allowed for prenatal diagnosis in some subtypes by ultrastructural examination of uncultured amniotic cells (late infantile type) and endothelial cells of biopsied chorionic stromal vessels (infantile type) (1).

Immunohistochemical studies have shown the accumulation of the subunit C of mitochondrial ATPase in the late infantile, juvenile and occassionally the adult type. Accumulation of sphingolipid activator proteins saposins A and D has been shown in the infantile type and to a lesser degree in the other subtypes (2).

In the past few years a great deal of progress has been made in assigning the subtypes to different chromosomal loci. The infantile type has been assigned to chromosome 1 in a region which codes for the palmitoyl-protein thioesterase (PPT). This is a lysosomal enzyme that in vitro removes fatty acid pamitate residues from S-acylated proteins (3). A separate locus has been identified for the late infantile type while the gene locus of the juvenile subtypes has been identified on chromosome 16 (4).

References

Goebel H.H., Prenatal Ultrastructural Diagnosis in the Neuronal Ceroid Lipofuscinoses. Path Res Pract 1994; 190: 728-733.
Goebel H.H., Morphologic Diagnosis in Neuronal Ceroid Lipofuscinosis. Neuropediatrics, 1997; 28:67-69.
Hellsten E, Vesa J, Jalanko A, Peltonen L, From Locus to Cellular Disturbances: Positional Cloning of the Infantile Neuronal Ceroid Lipofuscinosis Gene. Neuropediatrics, 1997;28:9-11.
Goebel H.H., Gerhard L, Kominame E, Haltia M, Neuronal Ceroid Lipofuscinosis - Late Infantile or Jansky-Bielschowsky Type - Revisited. Brain Pathology, 1996; 6:225-228.

Reader's Comments

July 1998 Case-of-the-Month

Sections Clinical History Light and Electron Microscopy Diagnosis & Discussion Reader Feedback	Diagnosis: Neuronal ceroid lipofuscinosis, late infantile type Discussion: The neuronal ceroid lipofuscinoses are a group of progressive encephalopathies which are inherited in an autosomal recessive manner. Four main types are recognized: infantile, late infantile, juvenile and adult. Morphologically they are characterized by widespread accumulation of autofluorescent lipopigments inside and outside the central nervous system. In the infantile type the lipopigments are granular. The late infantile type shows characteristic curvilinear profiles. Fingerprint profiles are seen in the classical juvenile type while the adult type can be somewhat variable showing granular material and/or fingerprint profiles. Many cell types contain the abnormal inclusions including endothelial cells and amniotic fluid cells. This has allowed for prenatal diagnosis in some subtypes by ultrastructural examination of uncultured amniotic cells (late infantile type) and endothelial cells of biopsied chorionic stromal vessels (infantile type) (1). Immunohistochemical studies have shown the accumulation of the subunit C of mitochondrial ATPase in the late infantile, juvenile and occassionally the adult type. Accumulation of sphingolipid activator proteins saposins A and D has been shown in the infantile type and to a lesser degree in the other subtypes (2). In the past few years a great deal of progress has been made in assigning the subtypes to different chromosomal loci. The infantile type has been assigned to chromosome 1 in a region which codes for the palmitoyl-protein thioesterase (PPT). This is a lysosomal enzyme that in vitro removes fatty acid pamitate residues from S-acylated proteins (3). A separate locus has been identified for the late infantile type while the gene locus of the juvenile subtypes has been identified on chromosome 16 (4). References Goebel H.H., Prenatal Ultrastructural Diagnosis in the Neuronal Ceroid Lipofuscinoses. Path Res Pract 1994; 190: 728-733. Goebel H.H., Morphologic Diagnosis in Neuronal Ceroid Lipofuscinosis. Neuropediatrics, 1997; 28:67-69. Hellsten E, Vesa J, Jalanko A, Peltonen L, From Locus to Cellular Disturbances: Positional Cloning of the Infantile Neuronal Ceroid Lipofuscinosis Gene. Neuropediatrics, 1997;28:9-11. Goebel H.H., Gerhard L, Kominame E, Haltia M, Neuronal Ceroid Lipofuscinosis - Late Infantile or Jansky-Bielschowsky Type - Revisited. Brain Pathology, 1996; 6:225-228.
	Reader's Comments

July 1998 Case-of-the-Month