Diagnosis of Fabry Disease Using Alpha-Galactosidase A Activity or LysoGb3 in Blood Fails to Identify Up to Two Thirds of Female Patients.

Anderson-Fabry disease is a lysosomal storage disorder caused by mutations in the GLA gene, which encodes the enzyme α-galactosidase A. The GLA gene is located on the X-chromosome, causing an X-linked pathology: due to lyonization, female patients usually manifest a variable symptomatology, ranging from asymptomatic to severe phenotypes. The confirmation of the clinical diagnosis of Fabry disease, achieved by measuring α-galactosidase A activity, which is usually the first test used, shows differences between male and female patients. This assay is reliable in male patients with causative mutations in the GLA gene, in whom the enzymatic activity is lower than normal values; on the other hand, in female Fabry patients, the enzymatic activity is extremely variable between normal and pathological values. These fluctuations are also found in female patients' blood levels of globotriaosylsphingosine (LysoGb3) for the same reason. In this paper, we present a retrospective study conducted in our laboratories on 827 Fabry patients with causative mutations in the GLA gene. Our results show that 100% of male patients had α-galactosidase A activity below the reference value, while more than 70% of female patients had normal values. It can also be observed that almost half of the female patients with pathogenic mutations in the GLA gene showed normal values of LysoGb3 in blood. Furthermore, in women, blood LysoGb3 values can vary over time, as we show in a clinical case presented in this paper. Both these tests could lead to missed diagnoses of Fabry disease in female patients, so the analysis of the GLA gene represents the main diagnostic test for Fabry disease in women to date.

Two Cases of Malingered Crime-Related Amnesia.

Amnesia is a frequent claim in major crimes, and it is estimated that the complete or partial absence of memory following a crime ranges from 25% to 50% of total cases. Although some cases may constitute a genuine form of amnesia, due to organic-neurological defects or psychological causes, and possibly combined with a dissociative or repressive coping style after an extreme experience, malingering is still fairly common in offenders. Therefore, one of the main goals in medico-legal proceedings is to find methods to determine the credibility of crime-related amnesia. At present, a number of lie and memory detection techniques can assist the forensic assessment of the reliability of declarative proof, and have been devised and improved over the past century: for example, modern polygraphs, event-related potentials, thermal imaging, functional magnetic resonance imaging, kinematic, and facial analysis. Other ad hoc psychological tests, such as the so-called Symptom Validity Test (SVT) and Performance Validity Test (PVT), as well as the autobiographical Implicit Association Test (aIAT), can also be used. To date, however, there is little evidence or case reports that document their real usefulness in forensic practice. Here, we report two cases of crime-related amnesia, whereby both defendants, who were found guilty of homicide, appeared to exhibit dissociative amnesia but where the application of SVTs, PVTs, and aIAT detected a malingered amnesia.