Low molecular weight urinary peptides in ceroid‐lipofuscinoses: Potential biochemical markers for the juvenile subtype

Abstract

AbstractUrine from patients with classical and atypical forms of juvenile ceroid‐lipofuscinosis (CL) was analyzed for the presence of diseasespecific peptides. Two distinct peptide paterns were recognized on lithium dodecyl sulfate polyacrylamide gel electrophoresis in classical juvenile CL Patients. Pattern 1 consisted of a single, intensely staining peptide of apparent Mr 2,000 and up to 4 heterogeneous, weakly staining peptides between 2,500 and 6,300 Mr. This peptide pattern was not seen in over 30 samples from patients with other neurodegenerative disorders, nor in normal control individuals. Reduced amounts of the 2,000 Mr Peptide were seen in 2 of 3 female heterozygotes whose children had the peptide pattern 1. The presence of large amounts of the 2,000 Mr peptide in urine extracts made patient identification unequivocal. Pattern 2 had 2 to 3 intensely staining peptide of 3,800, 5,000 and 7,000 Mr, a variable number of minor bands, and diffuse staining above 7,000 and below 3,800 Mr. Parents had 2 to 3 weakly staining peptides with molecular weights similar to the major bands seen in the patients. No consistent peptide pattern was seen in 8 patients with atypical CL. Late infantile CL patients had no or very small amounts of low Mr urinary peptides.The urinary components stained well with silver, poorly with coomassie Blue, and were digested by a nuclease‐free protease, as expected for protein. They were distinctly different from the peptides isolated from ovine CL tissues. Amino acid composition analysis showed a predominantly normal spectrum of amino acids.Patients could not be consistently distinguished from individuals with other neurodegenerative disorders based on urinary dolichol levels. However, 10 of 11 patients with classical juvenile CL could be diagnosed based on their urinary peptide patterns. Heterogeneity in the number, amount, and Mr of urinary peptides was observed within and between subtypes and sibships. It was concluded that demonstration of specific low Mr peptide pattern 1 and the more heterogeneous peptide pattern 2 in urines may aid in the diagnosis of juvenile CL.