A new Indian family affected by gelsolin amyloidosis
Boby Varkey Maramattom1, Yasha T Chickabasaviah2 1 Department of Neurology, Lourdes Hospital, Kochi, Kerala, India 2 Department of Neuropathology, NIMHANS, Bengaluru, Karnataka, India
Date of Submission
18-Nov-2013
Date of Decision
27-Nov-2013
Date of Acceptance
21-Dec-2013
Date of Web Publication
20-Jan-2014
Correspondence Address: Boby Varkey Maramattom Department of Neurology, Lourdes Hospital, Kochi, Kerala India
Source of Support: None, Conflict of Interest: None
How to cite this article: Maramattom BV, Chickabasaviah YT. A new Indian family affected by gelsolin amyloidosis. Neurol India 2013;61:673-5
How to cite this URL: Maramattom BV, Chickabasaviah YT. A new Indian family affected by gelsolin amyloidosis. Neurol India [serial online] 2013 [cited 2023 Sep 27];61:673-5. Available from: https://www.neurologyindia.com/text.asp?2013/61/6/673/125372
Sir,
Gelsolin amyloidos (GA), familial amyloid polyneuropathy type IV, is a rare familial amyloidosis of the Finnish type described by Meretoja. [1] This report describes the first Indian family of GA.
A 54-year-old man presented with facial twitching of 1-2 years duration. Examination revealed bifacial paresis (lower > upper face), cutis laxa (CL) of face and trunk, twitching of lower facial muscles and dysarthria [Figure 1]. Seven family members had a similar phenotype [Video 1] [Figure 2]. Most of them had developed the facial changes in their fifth decades. Slit lamp examination showed corneal Lattice dystrophy type II in the patient and his daughter [Figure 3]. Magnetic resonance imaging of brain and spine were normal. Superficial radial nerve biopsies showed multifocal amyloid deposits in the perineurium > endoneurium > epineurial blood vessel wall of the nerve. The endoneurial deposits were mainly perivascular [Figure 4]. Genetic testing was unaffordable.
GA is a rare autosomal dominant disease. Amyloid in these patients is formed from the protein product of the gelsolin gene. Gelsolin is a cytosolic protein associated with actin with both intracellular and extracellular functions. [2] A mutation in the gelsolin coding area (q32-34) of chromosome 9 produces an abnormal gelsolin fragment that leads to self-sustaining amyloidogenesis and systemic deposition with disruption of basement membranes in various structures. [3],[4],[5]
Figure 1: Photographs of Proband (Panel a) and his younger brother (8th sibling) (Panel b) show saggy facies and dermatochalasis with smooth brows. Panel c shows cutis laxa. Panel d shows the 'plucked chicken appearance of the skin over the neck'
Figure 3: Panel A - slit lamp photograph of the cornea shows corneal anterior stromal dystrophy; both lattice and granular deposits suggestive of Lattice dystrophy type II. Panel B - slit lamp photograph of the daughter's cornea shows amyloid deposits consistent with Lattice dystrophy. Panel C - fundus photography shows normal optic discs with mild superior retinal nerve fiber defects
Figure 4: Superficial radial nerve biopsy. (a) Large eosinophilic amyloid deposits in the perineurium of a small nerve funicle (asterisk). (b) Deposit exhibits apple green birefringence under the polarizer. (c) An epineurial vessel (arrow) and perineurium (arrowhead) show amyloid deposits. (a: H and E, original magnification ×160; b and c: Congo red, original magnification ×160)
GA starts in the third decade of life with corneal lattice dystrophy. [6] Upper facial paresis followed by lower facial paresis is then seen. Lower cranial nerves including the IX, X and XII nerves can be involved. Peripheral and autonomic nerves are mildly affected. [3] GA deposition in the basement membrane of the skin produces CL, pruritis, hypohidrosis, easy bruisability, dermatochalasia and macroglossia. [7] Late stage systemic involvement leads to renal amyloidosis, cardiac conduction abnormalities or cerebral amyloid angiopathy. [3],[8] Histopathological examination reveals amyloid deposition in the perineurial sheaths and vessel walls especially in the nerve roots. [9] Amyloid is found in the cornea, conjunctiva, sclera, nerves and vessels in the eye. Mutation analysis is definitive; however it is expensive. In conclusion, we have described the first family of GA from India.
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Hereditary gelsolin amyloidosis: a rare cause of cranial, peripheral and autonomic neuropathies linked to D187N and Y447H substitutions
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