TY - JOUR
T1 - Electroretinographic and clinicopathologic correlations of retinal dysfunction in infantile neuronal ceroid lipofuscinosis (infantile Batten disease)
AU - Weleber, Richard G.
AU - Gupta, Nisha
AU - Trzupek, Karmen M.
AU - Wepner, Meredith S.
AU - Kurz, Daryl E.
AU - Milam, Ann H.
N1 - Funding Information:
This study was supported in part by The Foundation Fighting Blindness, Owings Mills, MD, Research to Prevent Blindness, New York, NY, Pennsylvania Lions Sight Conservation and Eye Research Foundation, Feasterville, Pennsylvania, Paul and Evanina Mackall Trust, New York, NY, and the F.M. Kirby Foundation, Morristown, NJ.
PY - 2004/9
Y1 - 2004/9
N2 - 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.
AB - 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.
KW - CLN1
KW - Electroretinogram
KW - Infantile neuronal ceroid lipofuscinosis
KW - Lysosomal storage diseases
KW - PPT1
KW - Palmitoyl-protein thioesterase-1
KW - Pathology
KW - Retinal degeneration
UR - http://www.scopus.com/inward/record.url?scp=4744361095&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4744361095&partnerID=8YFLogxK
U2 - 10.1016/j.ymgme.2004.06.019
DO - 10.1016/j.ymgme.2004.06.019
M3 - Conference article
C2 - 15464427
AN - SCOPUS:4744361095
SN - 1096-7192
VL - 83
SP - 128
EP - 137
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 1-2
T2 - ASHG 2004 Meeting Toronto
Y2 - 26 October 2004 through 26 October 2004
ER -