|Year : 2016 | Volume
| Issue : 3 | Page : 133-135
Need for interprofessional collaborative practice: Lafora disease
Melba Sheila D'Souza, Anandhi Amirthraj
Department of Adult Health and Critical Care, College of Nursing, Sultan Qaboos University, Muscat, Sultanate of Oman
|Date of Submission||09-Feb-2016|
|Date of Acceptance||17-Mar-2016|
|Date of Web Publication||23-Jun-2016|
Dr. Melba Sheila D'Souza
College of Nursing, Sultan Qaboos University, P. O. Box: 66, Muscat
Sultanate of Oman
Source of Support: None, Conflict of Interest: None
| Abstract|| |
A 19-year adolescent presented to a specialist hospital with a 5-year history of Lafora disease (LD) or progressive myoclonic epilepsy. LD (EPM2) resulting from a homozygous missense mutation in EPM2B (NHLRC1) was confirmed. Symptomatic management was done using conventional anti- epileptics and anti-myoclonics. Understanding the nature of prenatal screening and genetic alliance are an important for advocating genetic testing and genetic counseling. This framework is necessary for a transdisciplinary, preventive genetic services, and likely gene therapy.
Keywords: EPM2B, genetic alliance, genetic counseling, genetic testing, Lafora disease, prenatal screening, progressive myoclonic epilepsy
|How to cite this article:|
D'Souza MS, Amirthraj A. Need for interprofessional collaborative practice: Lafora disease. Int J Nutr Pharmacol Neurol Dis 2016;6:133-5
|How to cite this URL:|
D'Souza MS, Amirthraj A. Need for interprofessional collaborative practice: Lafora disease. Int J Nutr Pharmacol Neurol Dis [serial online] 2016 [cited 2020 Mar 31];6:133-5. Available from: http://www.ijnpnd.com/text.asp?2016/6/3/133/184596
| Introduction|| |
In 2015, a 19-year-male adolescent presented with symptoms of myoclonic seizure and speech disorders. He was a full term normal vaginal delivery, with no history of complicated pregnancy or delivery. He had normal neuro-psychomotor development during childhood, regular schooling and healthy until the age of 13 years. His Omani parents were first-degree cousins, had a consanguineous marriage and were carriers of Lafora disease (LD). His mother's five brothers were affected by LD and died as infants. His two brothers were affected with LD, and two brothers were unaffected. He had inherited a mutation in both copies of the responsible gene in each cell (mother and father mutated gene). He initially exhibited recurrent seizures, sudden transient blindness, dysarthria, ataxia, frequent myoclonic jerks in the legs, and severe dementia at the age of 14 years.
This adolescent boy had a strong familial tendency, age at onset, typical symptoms, rapid worsening of cognitive function, confirmed by microscopy of the axillary skin biopsy with detection of Lafora bodies (LBs) (poly glucosan aggregates) or periodic acid-Schiff positive inclusion bodies in the abluminal side of the apocrine sweat gland acini. Genetic molecular screening indicated homozygous R241X mutation in EPM2A, causative mutation of this gene. Electroencephalography showed disorganized generalized high-voltage spike-wave complexes. Cranial magnetic resonance imaging showed mild frontal cortex abnormalities, cerebral, and cerebellar atrophy and hydrocephalus. He was confirmed with the diagnosis of LD at 14 years.
| Case Report|| |
At the start of the disease, this 19-year-male adolescent had seizures which were controlled by antiepileptics; but in the subsequent weeks, the frequency of seizures had increased with generalized tonic-clonic seizures, visual, or occipital seizures (causing transient blindness, and complex visual hallucinations), myoclonic seizures (asymmetric, segmental, constant, and massive myoclonic jerks) and severe mental decline. He exhibited rapidly progressive dementia/cognitive decline, apraxia, difficult speech behavioral change, depression, confusion, ataxia (difficulty controlling muscles), and dysarthria (motor speech disorder). His had increased learning difficulties and his school performance deteriorated. He had a blunt affect, speech difficulties, dysarthria, feeding difficulties, appendicular and truncal ataxia, difficulty to walk without assistance and had dementia. Later, his myoclonus was frequent during wakefulness in early morning and ceases with sleep. Over the next few months, he became akinetic, had severe loss of ability to perform activities of daily living, dementia, mute, general condition deteriorated, disabled, spastic quadriparesis, and slipped into unconsciousness toward the last 4 years.
On arrival at the hospital emergency department, he was in a state of loss of consciousness; hyperpyrexia had severe stridor, shallow respirations, and severe dyspnea. He was diagnosed to have status epilepticus, aspiration pneumonia, adult respiratory distress syndrome, and multi-organ dysfunction. He was unresponsive, hypotensive, had a cessation of breathing and ventricular fibrillation. There was no clinical improvement in his health status, and he had a sudden cardiac arrest leading to his death in the 5 th year from the time of diagnosis. His family had an ethical, informed consent, and decision-making about his clinical prognosis and had requested for do-not-resuscitate in the case of arrest.
| Discussion|| |
LD is the most severe form of progressive myoclonus epilepsy is a brain disorder, rare, and fatal autosomal recessive inherited genetic disorder [Figure 1]. , It is more frequent in ethnic isolates and in parts of the world with a high rate of consanguinity. It is characterized by intractable recurrent tonic-clonic seizures (epilepsy), myoclonus, ataxia, visual hallucinations, progressive dementia or decline in intellectual function and neurodegeneration in the late childhood or adolescence and early death. , It leads to death 2-10 years after clinical onset.  LBD occurs with mutations in either EPM2A gene or EPMB2B/NHLRC1 gene in 58% and 38% of cases, respectively.  Laforin and malin malfunctions result in the formation of abnormal glycogen (LB). , Increased levels of laforin bind to glycogen causing LB. ,, At the early stages of LBD, there is temporary symptomatic cure or management to slow the progression of the condition, only symptomatic treatment. As symptoms of LD aggravate with advancing age, corpora amylacea in neuroglia accumulated in large numbers and sizes in the glial feltwork immediately beneath the cerebral ventricles and pia mater. ,
|Figure 1: Two recent theories of the pathogenesis of Lafora bodies. (a) Glycogen synthase (light blue) extends the growing glycogen chain in a linear manner. Glycogen branching enzyme (green) branches the linear glycogen, giving the molecule its spherical shape. Laforin, malin, and possibly, other proteins involved in Lafora disease regulate the balance of the two enzymes, preventing polyglucosan formation. (b) Glycogen is normally phosphorylated, and this hinders its degradation. Laforin (yellow) dephosphorylates glycogen. If laforin or malin is not present, glycogen cannot be degraded and over time, it loses its spherical structure, accumulating as polyglucosans to form Lafora bodies. GBE1: Glycogen branching enzyme; GS: Glycogen synthase; P: Phosphate|
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Antioxidants and flavonoids in natural fruits, nuts, herbs, and vegetables aid in preventing neurodegenerative diseases through modulation of neurons.  Social, psychological, and nutritional support is needed for individuals and families for course of disease and coping with a lifelong illness and its consequences. Counseling improves locus of control and quality of life among caregivers.  Genetic counseling is critical for family members to have an informed knowledge on genetic transmission, history, treatment, mode of inheritance, genetic risks, and limitation of genetic testing. This may increase informed decision-making, caregiver support, and survival, improved access to treatment, increase knowledge and attitudes toward testing and diagnoses.
Gene-replacement therapies like replacement of missing genes like EPM2A through use of immunoliposome vectors are in progress.  This will help to provide better life expectancy for affected individuals with LBD. DNA banking of affected individuals for possible future use. Preimplantation genetic diagnosis is an option for some families with EPM2A or NHLRC1 pathogenic variants. Genotyping and genetic diagnosis are a key to diagnose LD and to guide caregivers in coping with children with LD for future generations. An interprofessional collaborative practice with a genetic counselor, neurologist, registered nurse, psychologist, social worker, pharmacist, physical therapist and occupational therapist are highly recommended while caring for children with Lafora disease.
The views expressed in this study do not necessarily represent the views of the unit and hospital. We are grateful to the medical specialists, nurses, and language editors.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Minassian BA. Lafora′s disease: Towards a clinical, pathologic, and molecular synthesis. Pediatr Neurol 2001;25:21-9.
Ramachandran N, Girard JM, Turnbull J, Minassian BA. The autosomal recessively inherited progressive myoclonus epilepsies and their genes. Epilepsia 2009;50 Suppl 5:29-36.
Lohi H, Turnbull J, Zhao XC, Pullenayegum S, Ianzano L, Yahyaoui M, et al.
Genetic diagnosis in Lafora disease: Genotype-phenotype correlations and diagnostic pitfalls. Neurology 2007;68:996-1001.
Delgado-Escueta AV. Advances in lafora progressive myoclonus epilepsy. Curr Neurol Neurosci Rep 2007;7:428-33.
Giraldez BG, Serratosa JM. Lafora disease. In: Atlas of Epilepsies. Springer-Verlag London: Springer; 2010. p. 1231-4.
Tiberia E, Turnbull J, Wang T, Ruggieri A, Zhao XC, Pencea N, et al.
Increased laforin and laforin binding to glycogen underlie Lafora body formation in malin-deficient Lafora disease. J Biol Chem 2012 20;287:25650-9.
Vilchez D, Ros S, Cifuentes D, Pujadas L, Vallès J, García-Fojeda B, et al.
Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy. Nat Neurosci 2007;10:1407-13.
Worby CA, Gentry MS, Dixon JE. Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG). J Biol Chem 2008;283:4069-76.
Solaz-Fuster MC, Gimeno-Alcañiz JV, Ros S, Fernandez-Sanchez ME, Garcia-Fojeda B, Criado Garcia O, et al.
Regulation of glycogen synthesis by the laforin-malin complex is modulated by the AMP-activated protein kinase pathway. Hum Mol Genet 2008;17:667-78.
Altindag E, Kara B, Baykan B, Terzibasioglu E, Sencer S, Onat L, et al.
MR spectroscopy findings in Lafora disease. J Neuroimaging 2009;19:359-65.
Essa MM, Subash S, Akbar M, Al-Adawi S, Guillemin GJ. Long-term dietary supplementation of pomegranates, figs and dates alleviate neuroinflammation in a transgenic mouse model of Alzheimer′s disease. PLoS One 2015;10:e0120964.
Durugkar S, Gujjarlamudi HB, Sewliker N. Quality of life in epileptic patients in doctor′s perspective. Int J Nutr Pharmacol Neurol Dis 2014;4:53.
Lohi H, Chan EM, Scherer SW, Minassian BA. On the road to tractability: The current biochemical understanding of progressive myoclonus epilepsies. Adv Neurol 2006;97:399-415.
Gentry MS, Dowen RH 3 rd
, Worby CA, Mattoo S, Ecker JR, Dixon JE. The phosphatase laforin crosses evolutionary boundaries and links carbohydrate metabolism to neuronal disease. J Cell Biol 2007;178:477-88.