The significance of opthalmologic evaluation in the early diagnosis of inborn errors of metabolism: the Cretan experience

BACKGROUND: The Inborn Errors of Metabolism (IEM) are far from the rare systemic diseases that mainly affect the neural tissue. There are very few written reports on ocular findings in subjects with IEM, thus it was interesting to study the frequency of ocular findings in the studied population and explore their contribution to the early diagnosis of IEM. METHODS: Our study involved the evaluation of IEM suspected cases, which had been identified in a rural population in Crete, Greece. Over a period of 3 years, 125 patients, who fulfilled the inclusion criteria of this study, were examined. Analytical physical examination, detailed laboratory investigation as well as a thorough ocular examination were made. RESULTS: A diagnosis of IEM was established in 23 of the 125 patients (18.4%). Ten (43.5%) of the diagnosed IEM had ocular findings, while 8 of them (34.8%) had findings which were specific for the diagnosed diseases. One patient diagnosed with glycogenosis type 1b presented a rare finding. Of the 102 non-diagnosed patients, 53 (51.96 %) presented various ophthalmic findings, some of which could be related to a metabolic disease and therefore may be very helpful in the future. CONCLUSIONS: The ocular investigation can be extremely useful for raising the suspicion and the establishment of an early diagnosis of IEM. It could also add new findings related to these diseases. The early management of the ocular symptoms can improve the quality of life to these patients

CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

Objective: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. Methods: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. Results: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a wellbehaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. Conclusions: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. Copyright © 2012 by AAN Enterprises, Inc