Anderson-Fabry Disease: A Rare Disease That Mimics Common Cardiac, Neurological, Renal, and Other Disorders: Approach for the Differential Diagnosis and Follow-Up

Abstract Anderson-Fabry disease (AFD) is a rare inherited X-linked disease, caused by mutations of the gene encoding the α-galactosidase A enzyme, that leads to a deficiency or absence of its activity with consequent accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in the lysosomes of several cells types in the organism, mainly the endothelial, nervous system, cardiac, and renal cells. Its heterogeneous and nonspecific presentation, similar to other common pathologies, delays the diagnosis and leads to incorrect therapy. In the presence of attenuated phenotypes with predominant involvement of an organ, it is even harder to identify patients with AFD. It is highly important to be aware of this diagnosis, since enzyme replacement therapy is currently available. This review aims to approach the clinical manifestations of AFD and the phenotypes related to the differential diagnosis for each manifestation and the frequency of follow-up recommended.

Toxic leucoencephalopathy after 'chasing the dragon'

Toxic leucoencephalopathy (TLE) is a rare neurological complication of heroin abuse. 'Chasing the dragon' is an inhalational mode of heroin abuse that originated in Southeast Asia. Intriguingly, no cases of TLE have been reported from this region, although the inhalational mode of heroin abuse is common. We herein report the case of a middle-aged man with a history of polysubstance abuse who presented with progressive neurological symptoms and progressed to an uncommunicative state. While the initial impression was that of iatrogenic parkinsonism, diffuse leucoencephalopathy with sparing of the cerebellum was noted on magnetic resonance imaging. In view of his history of inhalational heroin abuse close to the onset of the neurological symptoms, a diagnosis of TLE was made. No clinical improvement was noted with administration of a dopaminergic agent. This is the first known case of delayed TLE following heroin inhalation from Southeast Asia with the unusual feature of cerebellar sparing.

Progressive multifocal leucoencephalopathy in HIV/AIDS: Observational study from a tertiary care centre in northern India.

Background & objectives: Progressive multifocal leucoencephalopathy (PML) is seen mostly in advanced human immunodeficiency virus (HIV) infection. Little is known about the epidemiology and disease course of these patients from India. This study was aimed to determine the frequency of PML in patients with HIV/AIDS, and the clinical features and survival of these patients. Methods: The charts of HIV/AIDS patients with PML seen over a period of five years (2006-2011) at the Antiretroviral treatment (ART) centre at a tertiary care centre in New Delhi, India, were retrospectively reviewed. Results: Of 1465 patients with HIV/AIDS, 18 (1.2%) were diagnosed with PML; four were laboratory confirmed and 14 had consistent clinical and radiological features. PML was the initial presentation of HIV infection in 10 (56%) patients, and 16 (89%) patients had CD4 count less than 200/μl. Insidious onset focal limb weakness (78%) and visual disturbance (28%) were common symptoms. Magnetic resonance imaging (MRI) of the brain revealed characteristic white matter lesions in all the patients. The estimated median survival was 7.6 months (95% CI, 0-20 months). Interpretation & conclusions: Our results show that the patients present late to access treatment with advanced immunosuppression at presentation. PML is associated with high morbidity and mortality despite institution of highly active antiretroviral therapy (HAART). There is a need to address the lacuna in diagnostic and management services for these patients in India.

Use of John Cunningham virus polymerase chain reaction in the diagnosis of progressive multifocal leucoencephalopathy - A rare presenting manifestation in an HIV-positive patient.

John Cunningham virus infection is an important cause of progressive multifocal leucoencephalopathy (PML) in the context of advanced human immunodeficiency virus infection. Limited data are available regarding the true incidence of PML as a presenting manifestation of HIV. We report one such case and also highlight the effective use of polymerase chain reaction in confirming its diagnosis.

Leucoencefalopatía hipóxico-isquémica retardada: caso clínico y revisión de la literatura / Hypoxic-ischemic delayed leukoencephalopathy: case report and review of the literature

Delayed Hypoxic-isquemic Leucoencephalopathy described in 1976 by Ginsberg is a brain white matter demyelinization phenomenon that occurred days or weeks after a hypoxic-isquemic injury followed by a complete recovery of the episode. The pathogenesis process remains unknown. We describe a 48 year old woman with cervico-uterine cancer in palliative treatment with opoids. She enters the emergency room with a respiratory depression, a prolonged hypotension and confusion, that it was recovered. At admission exhibits a recurrent pneumonia. Two weeks later, in conditions of discharge, initiates with agitation in context with rapidly progressive decline cognition, with concordant lesions of Leucoencephalopathy defined in the Magnetic Resonance (MR) study The metabolic profile, the cerebrospinal fluid and the electroencephalogram allowed dismissing other etiologic hypothesis. In front to the suspicious of Ginsberg syndrome, she had normal levels of Arylsulfatase. This acute post-hypoxic demyelinization process has been pathogenic interpreted as an arylsulfatase deficiency. Although numerous cases develop with normal arylsulfatase and the experimental studies of hypoxia, has support the hypothesis of a central hypoxic axonopathy due to failing in axonal transport as the base of the demyelinization phenomenal.

La leucoencefalopatía hipóxico-isquémica retardada (EHIR), descrita por Ginsberg en el año 1976, es un fenómeno desmielinizante de la sustancia blanca cerebral, que se origina días o semanas después de un daño hipóxico-isquémico que había sido seguido de una recuperación completa del episodio. La patogenia del proceso no está completamente establecida. Se presenta una mujer de 48 años portadora de cáncer cérvicouterino, en tratamiento paliativo con opiáceos. Ingresa al Servicio de Urgencia por una depresión respiratoria, hipotensión prolongada y compromiso de conciencia, donde es recuperada. Se hospitaliza por una neumopatía intercúrrente. Dos semanas más tarde, estando en condiciones de alta, se inicia agitación psicomotora en el contexto de un deterioro cognitivo rápidamente progresivo, que el estudio de Resonancia Magnética (RM) definió como lesiones concordantes con una leucoencefalopatía. El perfil metabólico, el líquido cefalorraquídeo y el electroencefalograma, permitieron descartar otras hipótesis etiológicas. Frente a la sospecha de un síndrome de Ginsberg, los niveles de arilsulfatasa fueron normales. Este proceso desmielinizante agudo post-hipóxico, ha sido interpretado patogénicamente como un déficit de arilsulfatasa. Sin embargo, la existencia de numerosos casos que cursan con arilsulfatasa normal y los estudios experimentales de hipoxia, ha avalado la hipótesis de una axonopatía central hipóxica, atribuible a fallas del transporte axoplásmico, como base para el fenómeno desmielinizante.