The pulvinar sign in Fabry patients: the first report in female patients

Abstract

Dear Sirs,Fabry disease is a progressive X-linked lysosomal disordercaused by a deficiency of the enzyme a-galactosidaseA, resulting in the accumulation of glycosphingolipidsespecially in the kidney, heart, and nervous system. Clas-sically, affected males present the most severe signs of thedisease, but female patients may show a wide spectrum ofsymptoms, ranging from mild to severe, despite the pres-ence of normal enzyme activity [1]. Brain magnetic reso-nance imaging (MRI) studies have revealed severalneuroradiologic findings in Fabry patients, such as whitematter abnormalities, territorial or lacunar ischemic strokesand an increased tortuosity of the basilar artery [1].Interestingly, a peculiar T1-weighted hyperintensity of theposterior part of the thalamus (the so-called pulvinar sign)has been described in male patients [2–4].We studied four sisters, 22, 23, 26, 30 years old,respectively, (patients A, B, C, D) with genetically provenFabry disease (missense mutation: A292T). All fourpatients were studied as part of a family screening, becausetheir brother was recently diagnosed with Fabry disease.They presented with cornea verticillata, peripheral (neu-rophatic pain) and autonomic nervous system (hypohidro-sis) involvement. Patients B and C had microalbuminuria.No signs or symptoms of central nervous system involve-ment were detected.Patients A and B. Brain MRI revealed faint bilateralhyperintensity of the pulvinar in the youngest sisters(patients A and B) (Fig. 1).Angiokeratomas were identified in the periumbilicalregion. The ophthalmoscopic examination revealed corneaverticillata, and increased tortuosity of the retinal vesselswas detected in patient A. The cardiac function was nor-mal. Brain MRI did not show strokes or white matterabnormalities in the two patients.Patient A complained of neuropathic pain (since the ageof 14 years) with pain crises in hands and feet. Quantitativesensory testing showed abnormal results, with cold andheat hyperalgesia in lower limbs for either patients, andupper limbs for patient A. The kidney function was normal.Patient B had a peripheral neuropathy since the age of8 years, and abdominal pain with frequent episodes ofdiarrhea. Audiometry showed bilateral sensorineural hear-ing loss. Microalbuminuria was present.The pulvinar sign is mostly a bilateral neuroradiologicalsign which has been detected in T1-weighted MR imagesof the lateral part of the pulvinar of male Fabry patients[2–4]. It is considered expression of hyperperfusion with