Natural history of the late-onset phenotype of Fabry disease due to the p.F113L mutation.

BACKGROUND: The common GLA gene mutation p.F113L causes late-onset phenotype of Fabry disease (FD) with predominant cardiac manifestations. A founder effect of FD due to this mutation was found in the Portuguese region of Guimarães. Our study aims to deepen the knowledge on the natural history of this late-onset variant. METHODS: 203 consecutive adult Fabry patients with p.F113L mutation (79 males; mean age 46 ± 18 years), from this region, were submitted at baseline to a predefined diagnostic protocol. The occurrence of FD manifestations was analyzed in each decade of age in both genders. RESULTS: In males, left ventricular hypertrophy (40.2%) and late gadolinium enhancement (21.4%) arose over 30 years; heart failure (HF) (21.9%), ventricular tachycardia (8.9%) and conduction disorders over 40 years; and bifascicular (13.1%) and complete atrioventricular blocks (5.9%) beyond 50 years of age. Cardiac manifestations occurred more commonly and 1-2 decades earlier in males; their frequency increased with age. Septum and posterior wall thickness, LV mass, QRS interval duration and pro-BNP levels increased with age in both genders. Mean survival free from HF (64 ± 1 vs. 76 ± 2 years) and pacemaker (71 ± 2 vs. 86 ± 1 years) was higher in females (p < .001). Albuminuria A2/A3 (33.7%), brain white matter lesions (50.3%) and sensorineural deafness (44.7%) arose before 30 years of age in both genders, increasing with age. Renal failure and stroke were rare. Lysosomal inclusions were demonstrated in podocytes of patients with proteinuria. CONCLUSION: This study improves the knowledge on natural history of late-onset variants of FD, carrying major impact on clinical decisions and guidelines.

Extranodal natural killer/T cell lymphoma, nasal type: a diagnostic challenge.

Extranodal natural killer/T cell lymphoma, nasal type (ENKL) is a rare and aggressive tumour that can, clinically and histologically, mimic infectious and inflammatory conditions, presenting a diagnostic challenge. The authors report the case of a 69-year-old Portuguese woman previously misdiagnosed with chronic recurrent sinusitis. Despite maximal medical and surgical treatments, the disease was refractory and progressed. The patient had undergone multiple biopsies when the histopathological diagnosis of ENKL was made, 5 months after the initial complaints. Multiagent chemotherapy was offered, but during the first cycle, the patient developed severe infection and pancytopenia, which culminated in her death. This case highlights the need to consider a neoplastic cause when faced with aggressive sinonasal disease not responsive to maximal treatment and the difficulties in establishing the diagnosis of ENKL, with multiples biopsies of deep-tissue usually being required.

Pneumolabyrinth: a rare complication of stapes surgery.

Pneumolabyrinth is the entrapment of air within the inner ear and is a rare complication of stapes surgery. We report the case of a patient submitted to stapedectomy who, 4 weeks later, suddenly developed right hearing loss, ipsilateral tinnitus and vertigo. On the physical examination, the patient showed no signs of vestibular deficits. Audiometry was compatible with right profound mixed hearing loss and high-resolution CT of the temporal bone revealed the presence of pneumolabyrinth. During exploratory tympanotomy, the prosthesis was found dislodged; the communication between the middle and inner ear was closed with vein graft and a new prosthesis was placed. Following surgery, vestibular symptoms was abolished and the patient experienced great improvement of the hearing thresholds.