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DOI: 10.5146/tjpath.2021.01522 |
A Case of Lafora Disease Diagnosed by Axillary Skin Biopsy |
Elife KIMILOĞLU1, Pelin AKBAŞ1, Özgül ESEN ÖRE2, Çağla TURAN2 |
1Department of Pathology, Health Sciences University, Istanbul Gaziosmanpasa Research and Training Hospital, İSTANBUL, TURKEY 2Department of Neurology, Health Sciences University, Istanbul Gaziosmanpasa Research and Training Hospital, İSTANBUL, TURKEY |
Keywords: Lafora disease, Skin biopsy, Epilepsy |
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Lafora disease is a severe form of progressive myoclonic epilepsy with autosomal recessive inheritance diagnosed by inclusion body in biopsy.
A 26-year-old woman was admitted due to complaints of frequent twitches and fainting. The 0.5x0.3x0.3 cm axillary skin punch biopsy was
subjected to routine histopathological evaluation. Cytoplasmic PAS-positive inclusion bodies were observed at the basal side of the eccrine and
apocrine glands. The diagnosis of Lafora disease can also be made by the observation of the polyglycosan cytoplasmic inclusion bodies in the
brain, liver and skeletal muscle biopsies. Although we need more work to understand the etiopathogenesis of Lafora disease, we would like to
draw attention to the importance of skin biopsy in the differential diagnosis of young patients with clinically refractory epilepsy, myoclonus, and
cognitive decline. |
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Lafora disease is a rare, autosomal recessive severe form
of progressive myoclonic epilepsy characterized by
myoclonus, focal-generalized seizures, and progressive
dementia (1,2,4). The presence of Periodic Acid-Schiff
stain positive inclusion bodies is diagnostic for Lafora
disease (1,3,4). In this article, we present and discuss the
case of a 26-year-old female patient who presented with the
complaints of contractions all over her body, increasingly
frequent twitches in the eyes and shoulders for the last 2-3
days, and frequent fainting. |
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Abstract
Introduction
Case Presentation
Disscussion
References
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A 26-year-old woman was admitted due to complaints of
frequent twitches and fainting. She had experienced these
gradually worsening twitches for 11 years, she had repeated
every academic year twice until the third year of school,
she could not learn how to read or write, her parents
were relatives, and her brother had died at the age of 37
and had also suffered from epilepsy. She was currently
taking 1500 mg/day valproic acid, 200 mg/day phenytoin,
and 1000 mg/day levetiracetam for seizure control. She
was not using her medication regularly. Her neurological
examination showed frequent twitches in the eyelids,
shoulders and feet. Cerebellar tests could not be evaluated
due to bilateral myoclonus. In the EEG, severe generalized
disorganization was observed with generalized spike wave
discharges accompanied by myoclonus. The skin was
biopsied and sent to the pathology lab to find the etiology of this persistent, medication-resistant seizure disorder. The
0.5x0.3x0.3 cm axillary skin punch biopsy was subjected to
routine histopathological evaluation. No histopathological
abnormalities were observed when the paraffin-embedded
sections were stained with H&E, but staining with Periodic
Acid-Schiff revealed cytoplasmic PAS-positive inclusion
bodies at the basal side of the eccrine and apocrine glands
(Figure 1, 2).
 Click Here to Zoom |
Figure 1: Biopsy from axillary region shows intracytoplasmic
spherical inclusions (arrows) in the sweat gland duct (H&E; 200). |
 Click Here to Zoom |
Figure 2: PAS positive inclusion bodies (arrows) in apocrine
glands (PAS; x200). |
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Top
Abstract
Introduction
Case Presentation
Disscussion
References
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Lafora bodies seen in light microscopy of skin biopsy
when taken in accordance with appropriate clinical data
are diagnostic for Lafora Disease. The presence of Lafora
bodies alone, independent of the clinical context, is not
diagnostic (1). As discussed earlier, similar appearances
can also be seen in other diseases and some physiological
bodily processes. These bodies may be seen in diseases
such as double athetosis, ALS, type 4 glycogen depot
disease, and adult polyglycosan body disease, whereas
similar polyglycosan bodies can also be seen in the normal
aging process as corpora amylacea (5). Therefore, current
histopathologic data should not be evaluated independent
of the clinical context. The PAS positive staining of these
bodies, as we have shown in our case, indicates that they
are carbohydrate-rich at significant levels (3,4,6,7). Former
electron microscopic evaluations have shown that the
Lafora body is almost entirely composed of complex
glucose molecules, indicating that the carbohydrate content
is almost entirely polyglycosan (glucose polysaccharides) (1,8). EPM2A (6q24), EPM2B (6q22.3) and PRDM8
(shown only in one family) are said to be responsible for
the mutation that cause these polyglycosans to accumulate
(2). The diagnosis of Lafora disease can also be made by
the observation of the polyglycosan cytoplasmic inclusion
bodies in the brain, liver, and skeletal muscle biopsies
(1,5,8). On the other hand, polyglycosan bodies seen in
Lafora disease are separated from other diseases in which
polyglycosan bodies are also observed, by the location
of accumulation. In Lafora disease, polyglycosan bodies
are concentrated on the perikaryon and dendrites area of
the neuron while in adult polyglycosan body disease and
corpora amylacea, the polyglycosan bodies are limited to
the axonal region (1). Why they do not proceed along the
same path as the other polyglycosans is curious in Lafora
Disease. Although we need more work to understand the
etiopathogenesis of Lafora disease, we would like to draw
attention to the importance of skin biopsy in the differential
diagnosis of young patients with clinically refractory
epilepsy, myoclonus, and cognitive decline.
CONFLICT of INTEREST
The authors declare no conflict of interest.
AUTHORSHIP CONTRIBUTIONS
Concept: EK, PA, Design: PA, Data collection or processing:
PA, ÖEÖ, ÇT, Analysis or Interpretation: EK, PA, Literature
search: PA, Writing: PA, EK, Approval: EK. |
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Abstract
Introduction
Case Presentation
Discussion
References
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1) Minassian, BA. Lafora’s disease: Towards a clinical, pathologic,
and molecular synthesis. Pediatr Neurol. 2001;25:21-9.
2) Baykan B, Striano P, Gianotti S, Bebek N, Gennaro E, Gurses C,
Zara F. Late‐onset and slow‐progressing Lafora disease in four
siblings with EPM2B mutation. Epilepsia. 2005;46:1695-7.
3) Karmipour D, Lowe L, Blaivas M, Sachs D, Johnson TM.
Lafora disease: Diagnosis by skin biopsy. J Am Acad Dermatol.
1999;41:790-2.
4) Whie JW Jr, Gomez MR. Diagnosis of Lafora disease by skin
biopsy. J Cutan Pathol. 1988;15:171-5.
5) Turnbull J, Tiberia E, Striano P, Genton P, Carpenter S, Ackerley
CA, Minassian BA. Lafora disease. Epileptic Disord. 2016;18:38-62.
6) Rubio G, Guijo CG, Mallada JJ, Cabello A, Merino AG. Diagnosis
by axilla skin biopsy in an early case of Lafora’s disease. J Neurol
Neurosurg Psychiatry. 1992;55:1084-5.
7) Sathiah P, Gochhait D, Dehuri P, Subramanian H. Diagnosis of
Lafora Disease by skin biopsy. J Clin Diagn Res. 2017;11:EJ01-
EJ02.
8) Ceuterick C, Martin JJ. Diagnostic role of skin or conjunctival
biopsies in neurological disorders: An update. J Neurol Sci.
1984;65:179-91. |
Top
Abstract
Introduction
Case Presentation
Discussion
References
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