Electroretinographic and clinicopathologic correlations of retinal dysfunction in infantile neuronal ceroid lipofuscinosis (infantile Batten disease)

Richard Weleber, Nisha Gupta, Karmen M. Trzupek, Meredith S. Wepner, Daryl E. Kurz, Ann H. Milam

Research output: Contribution to journalArticle

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Abstract

Infantile neuronal ceroid lipofuscinosis (INCL) is an autosomal recessive disease that results from deficiency of palmitoyl-protein thioesterase-1 (PPT1). INCL leads to retinal blindness, neurodegeneration, and early death. We studied the clinical features and electroretinogram (ERG) in three patients and histopathologic and immunofluorescence analyses of the retina in the third patient, who died at 3 years 2 months of age. The ERGs for the 2 youngest patients (ages 1.7 and 2.3 years) showed normal scotopic bright flash a-wave amplitudes with severe loss of b-wave (electronegative ERG), indicating dysfunction at or proximal to the photoreceptor inner segments. The third patient at 2.9 years of age showed subnormal a-wave amplitudes and even greater loss of b-wave amplitudes. Histopathology revealed reduced cell numbers in all retinal layers, including the inner nuclear layer (INL), and a central epiretinal membrane. Autofluorescent lipofuscin granules were present in all neuronal cell types in the retina. Cones and rods in the parafoveal area were labeled with a cone cytoplasmic marker, mAb 7G6, and anti-rhodopsin, respectively, and had extremely short outer segments. The periphery showed better preservation but photoreceptor outer segments were short. Immunofluorescence revealed degenerate rods and cones throughout the retina with better preservation in the periphery. Autofluorescent lipofuscin was found in all cell types, including cone inner segments, to a greater degree than seen in normal ageing. The ERG findings support the existence early in the disease of a relative pre- or post-synaptic block of effective neurotransmission from photoreceptor inner segments to the second order bipolar neurons.

Original languageEnglish (US)
Pages (from-to)128-137
Number of pages10
JournalMolecular Genetics and Metabolism
Volume83
Issue number1-2
DOIs
StatePublished - Sep 2004

Fingerprint

Ceroid
Neuronal Ceroid-Lipofuscinoses
Cones
Lipofuscin
Vertebrate Photoreceptor Cells
Fluorescent Antibody Technique
Retina
Retinal Photoreceptor Cell Inner Segment
Epiretinal Membrane
Retinal Cone Photoreceptor Cells
Deficiency Diseases
Rhodopsin
Blindness
Synaptic Transmission
Neurons
Cell Count
Aging of materials
Membranes
Ceroid lipofuscinosis, neuronal 1, infantile

Keywords

  • CLN1
  • Electroretinogram
  • Infantile neuronal ceroid lipofuscinosis
  • Lysosomal storage diseases
  • Palmitoyl-protein thioesterase-1
  • Pathology
  • PPT1
  • Retinal degeneration

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

Cite this

Electroretinographic and clinicopathologic correlations of retinal dysfunction in infantile neuronal ceroid lipofuscinosis (infantile Batten disease). / Weleber, Richard; Gupta, Nisha; Trzupek, Karmen M.; Wepner, Meredith S.; Kurz, Daryl E.; Milam, Ann H.

In: Molecular Genetics and Metabolism, Vol. 83, No. 1-2, 09.2004, p. 128-137.

Research output: Contribution to journalArticle

Weleber, Richard ; Gupta, Nisha ; Trzupek, Karmen M. ; Wepner, Meredith S. ; Kurz, Daryl E. ; Milam, Ann H. / Electroretinographic and clinicopathologic correlations of retinal dysfunction in infantile neuronal ceroid lipofuscinosis (infantile Batten disease). In: Molecular Genetics and Metabolism. 2004 ; Vol. 83, No. 1-2. pp. 128-137.
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