Printer Friendly

Medical and mental health complications of Lafora disease: a case report.

Lafora disease is a rare neurometabolic condition caused by a mutation in the EPM2A and/or EPM2B genes. The disorder is neurologically progressive, and the disease is eventually fatal. A form of progressive myoclonic epilepsy, it can produce a variety of complications including intellectual disability, various seizure disorders, mental health difficulties, and dementia. The authors describe the symptoms of Lafora disease; a case study of a young male who was diagnosed with the disorder is presented. The etiology of Lafora disease and progression of the disorder are described. Implications for treatment of the disorder and palliative care are briefly discussed.

Keywords: dementia, developmental disability, intellectual disability, Lafora disease, mental retardation, progressive myoclonic epilepsy, psychiatric disorder

**********

Lafora disease (also known as Lafora Body disease) is a rare neurometabolic disorder of autosomal recessive inheritance, which is generally caused by a mutation in EPM2A (4,8,13) or EPM2B genes. (3,6,14) disorder is a fatal form of progressive myoclonic epilepsy. Since it is a disease of autosomal recessive inheritance, individuals can only contract the disorder if both parents are carriers of the mutant gene. Lafora disease is one of five major conditions that account for the majority of the progressive myoclonic epilepsies (i.e., Lafora disease, Unverricht-Lundborg disease , mitochondrial diseases, sialidosis, and neuronal ceroid lipofuscinosis). Symptoms usually begin within the first two decades of life. Intellectual disability is often found as the disease progresses and is also sometimes present prior to onset of symptoms. Although intellectual disability is often a comorbid condition found with the disorder, there is a dearth of information regarding the disorder as it pertains to persons with intellectual disabilities. There are a variety of mental health conditions that have been encountered with Lafora disease. Unfortunately, there is little information regarding mental health complications of the disorder in persons with intellectual disability.

The disorder was first described by Lafora and Guelkin in 1911. Clinical features of Lafora disease can be found in Table 1. Diagnosis is made by identification of Lafora bodies, which are polyglucosan inclusion bodies. These bodies can be found in the liver, neurons, skin, heart, skeletal muscles, and sweat gland cells. Because of the invasiveness of liver, heart, or skeletal muscle biopsies, diagnosis is usually confirmed by detecting Lafora bodies in the skin cells. In addition to mutation of the EPM2A and EPM2B genes, a third gene is thought to be involved in the disorder. Further research is being conducted in order to identify the third gene. Based on current knowledge of the disorder, up to 80% of individuals with Lafora disease have mutation of the EPM2A gene. Both the EPM2A and EPM2B genes are found on chromosome 6q. Chromosome 6 is responsible for coding two proteins, laforin and malin. (9) A slide of the Lafora body is presented in Figure 1. (11)

[FIGURE 1 OMITTED]

Lafora disease reportedly affects men and women in relatively equal numbers. Worldwide, it is considered a very rare disorder. It is reportedly most common in the Middle East, Southern Europe, and Northern Africa. It is found more frequently in countries in which consanguineous marriage more commonly occurs. (1,5) The disorder is also found in the United States, although prevalence is not known.

Most common clinical manifestations reported include seizures. Most often, generalized tonic-clonic and/or myoclonic seizures are the first symptoms reported. (7) Epileptic occipital lobe seizures and nonepileptic visual hallucinations have also been reported with Lafora disease. (2,7) Progressive neurological and cognitive deterioration occur with the disorder. Progressive neurological symptoms have been reported to include dysarthria, mutism, ataxia, paresis, and/or blindness. Increasingly poor seizure control occurs, which often results in status epilepticus. Respiratory failure secondary to seizures has been reported, as well as cardiac arrhythmia and arrest. A number of mental health manifestations have been reported including depression, psychosis, and personality changes. Dementia is common with the disorder, as well as intellectual disability.

TREATMENT

The primary focus of treatment is medication management for seizure control. Unfortunately, the disease is fatal and there is no specific treatment to "cure" the disorder. As the disease progresses, treatment takes the form of palliative care. Advances in gene therapy, stem cell research, or protein therapies might provide treatment in the future for this insidious disease. (12) One area of research is currently being conducted by the National Institutes of Health to determine if a diet limited in carbohydrates will slow progression of the disease and reduce formation of Lafora bodies. (10,12)

A case report of a young man with intellectual disability and Lafora disease is presented in order to provide further description of medical and psychological aspects of the disorder. It should be noted that the individual eventually died of complications secondary to Lafora disease. Since presentation of the case report involved the examination of archival records, approval to access patient files and present information was obtained from the treatment facility and State Human Subjects Institutional Review Board. Written consent was also obtained from the patient's guardian.

CASE REPORT

Mr. C was a Caucasian male who died from complications of Lafora disease at 27 years of age. He was reportedly conceived as the result of an incestuous relationship between a 13-year-old girl and her older brother. The patient was placed in foster care, and he was adopted when he was about 6 months old.

His records revealed that disruptive and destructive behaviors were first reported at 8 years old. The first neurological symptoms were also observed, as he exhibited difficulties with visual tracking. Mr. C was diagnosed with a complex partial seizure disorder. He began experiencing auditory hallucinations at 8 years old. His adoptive parents divorced when he was about age 11, and he later went to live with his adoptive father due to behavioral concerns. Because of increasing conduct problems, he was eventually placed in various community residences and treatment facilities for children with behavior disorders. A number of behavioral concerns were noted including assault of other patients and destruction of property. According to the patient's guardian, a number of factors likely contributed to behavioral difficulties including the divorce of his adoptive parents, bad experiences with a series of community placements, frustrations with decline in physical/cognitive abilities, and other effects of Lafora disease.

He was referred for psychological, psychiatric, and educational evaluation several times throughout childhood through early adulthood. He was diagnosed with a variety of disorders including reactive attachment disorder of early childhood, conduct disorder, pervasive developmental disorder NOS "with psychosis," intermittent explosive disorder, and learning disabilities in math and listening comprehension.

At age 14, he was court ordered to a state mental health facility for adolescents. He was then transferred to an adolescent community residence, and he was generally "compliant" with treatment. Occasional "anger outbursts" were noted, and some outbursts reportedly occurred for "no reason." According to records, professionals attributed outbursts with no identifiable antecedents as occurring secondary to "temporal lobe epilepsy."

At age 16, he was placed in a community residence. He was reportedly resistant to the program. He was assaultive to other patients, and he was also destructive to property. Frequent noncompliance with treatment was noted, and anger outbursts were sometimes unpredictable.

At age 18, he was placed at a state psychiatric facility due to disruptive behavior. He was diagnosed with "organic personality disorder," intermittent explosive disorder, mathematics disorder, expressive language disorder, and epilepsy. At the time of his admission to the inpatient facility, he was on several medications including valproic acid, clonazepam, felbamate, ethosuximide, and sertraline.

At age 23, he was transferred to a state institution for persons with intellectual disabilities. Medical staff ordered a skin biopsy for Mr. C, and Lafora disease was diagnosed. Seizure control became increasingly difficult for the patient. Medications prior to death included lorazepam, clonazepam, phenobarbital, valproic acid, lamotrigine, albuterol, and lorazepam PRN.

Intellectual abilities declined over a period of several years. Information regarding progression of cognitive decline is found in Table 2. At age 14, his intellectual abilities were in the low average range (WISC-III Full Scale IQ SS = 85). By age 18, cognitive abilities were in the moderate range of intellectual disability (WAIS-R Full Scale IQ SS = 55). At age 22, he was evaluated for continued eligibility for disability services. During his final evaluation, he was unable to respond to test stimuli; and the evaluator estimated his intellectual abilities in the severe to profound range of intellectual disability. Assessment of adaptive behavior was conducted during his final evaluation, and his score on the Inventory for Client and Agency Planning (ICAP) was severely impaired. His ICAP score placed him in a range of care requiring "total personal care and intense supervision."

The patient died at age 27 in a state institution for persons with intellectual disabilities. Placement at the state facility was required due to his intensive medical needs. Prior to death, his neurological and cognitive functioning continued to decline. He was nonambulatory, and needed total assistance with sitting and transfers. Mr. C was hypotonic, and deep tendon reflexes of lower extremities were absent. He needed assistance with eating, and a G-tube was required on occasion due to increased seizure activity. Low oxygen saturation was an ongoing problem due to seizure activity. The patient had recently been released from the hospital after his health reportedly improved following a bout of pneumonia. He was generally nonverbal, and was unresponsive to external stimuli. Seizures became increasingly difficult to control, and he went into a coma prior to death. The cause of death was reportedly respiratory failure secondary to Lafora disease.

DISCUSSION

Despite the inevitable problems with this disorder, there are still benefits to diagnosis. A number of factors might have contributed to behavioral difficulties including the divorce of his adoptive parents and poor success with a series of community placements. However, many of the behavioral and neurological manifestations could have been explained by the diagnosis of Lafora disease. Early diagnosis might have led to more effective and aggressive treatment for the patient. Proper diagnosis of Lafora disease could have changed habilitative planning for Mr. C, and arrangement of more appropriate community supports might have been possible.

In some cases, the diagnosis of a serious disorder such as Lafora disease can provide families with insight or "answers" to serious behavioral challenges. When behavioral difficulties appear in the absence of clear external antecedents, proper diagnosis of a disorder can provide validation for families that they are not the "cause" of the behavioral problems. In some cases, proper diagnosis of the disorder might provide a sense of closure for families. Unfortunately, professionals might not recognize or appreciate the importance of making the diagnosis of such a disorder, especially if there is no treatment that will assist the patient. However, diagnosis can prove beneficial for some families as it might provide a reason for the presence of behavioral difficulties, neurological deficits, and cognitive decline.

Lafora disease is an insidious form of myoclonic epilepsy that is very rare. Initial treatment focuses on seizure control through medication management. As the disease progresses, seizure control becomes less successful. During the final stage of the disorder, treatment for the disease is palliative in nature. Unfortunately, the disease is always fatal. In addition to presenting the medical aspects of the disorder, we have also striven to present mental health problems associated with the disorder. One of the more prominent symptoms of the disorder is the development of dementia. Treatment considerations include seizure control, medications to control psychiatric and neurological aspects of the disorder. Palliative care is necessary for the final stages of the disorder. Long-term prognosis for the patient is poor, and most patients die within 10 years of clinical findings.

Although the disease is much more frequent in Asia and Europe, cases are also reported in North America with unknown prevalence. However, it is likely that this disorder is underdiagnosed. As presented in our case study, the disorder was not diagnosed until about two years prior to Mr. C's death.

In some cases genetic tests can be conducted to diagnose the disorder. However, this procedure can be extremely expensive. In addition, genetic screening might not catch all cases of the disorder as it is believed that a third gene yet to be identified is also responsible for the Lafora disease. To date, skin biopsy appears to be the most effective, least intrusive procedure in diagnosing the disorder.

A number of mental health concerns have been reported in the literature, which can occur in conjunction with Lafora disease. Mental health problems reported include dementia, depression, and psychosis. As outlined in the case study, Mr. C exhibited several symptoms that have been reported in the literature. At times, his behavior was quite volatile. Environmental factors influenced mental health problems to some degree. Unfortunately, the likely etiology of many of his health concerns was also the presence of a rare disorder. As has been presented, he was diagnosed with a variety of mental health conditions. We have attempted to outline symptoms of Lafora disease in order to educate professionals as to the medical and mental health aspects of this condition.

ACKNOWLEDGMENTS: We wish to thank Mr. C's guardian for her permission to review records regarding Mr. C and providing us the opportunity to share information regarding his life and care.

REFERENCES

(1.) Acharya JN, Satischandra P, Asha T, Shankar SK. Lafora's disease in south India: A clinical, electrophysiologic, and pathologic study. Epilepsia 1993;34:476-487.

(2.) Andrade DM, del Campo JM, Moro E, et al. Nonepileptic visual hallucinations in Lafora disease. Neurology 2005;64:1311-1312.

(3.) Baykan B, Striano P, Gianotti S, et al. Late-onset and slow-progressing Lafora disease in four siblings with EPM2B mutation. Epilepsia 2005;46:1695-1697.

(4.) Erbay H, Balci C, Tomatir E, et al. Refractory status epilepticus in intensive care unit: A case of Lafora body disease. Inter J Emer Inten Care Med 2003;E6(2):[on-line serial].

(5.) Ganesh S, Delgado-Escueta AV, Suzuki T, et al. Genotype-phenotype correlations for EPM2A mutations in Lafora's progressive myoclonus epilepsy: Exon 1 mutations associate with an early-onset cognitive deficit subphenotype. Hum Mol Genet 2002;11:1263-1271.

(6.) Gomez-Abad C, Gomez-Garre P, Gutierrez-Delicado E, et al. Lafora disease due to EPM2B mutations: A clinical and genetic study. Neurology 2005;64:982-986.

(7.) Koc AF, Bozdemir H, Zorludemir S, et al. Lafora body disease: Clinical, electrophysiological and histopathological findings. Turk J Med Sci 2004;34:379-384.

(8.) Minassian BA, Ianzano L, Meloche M, et al. Mutation spectrum and predicted function of laforin in Lafora's progressive myoclonus epilepsy. Neurology 2000;55:341-346.

(9.) Minassian BA. Lafora's disease: Towards a clinical, pathologic, and molecular synthesis. Pediatr Neurol 2001;25:21-29.

(10.) Minassian BA. Progressive myoclonus epilepsy with polyglucosan bodies: Lafora disease. Adv Neurol 2002;89:199-210.

(11.) Rosenblum WI. Neuropathology Mini-Course for Residents. Virginia Commonwealth University, 2005 [on-line course].

(12.) Shahwan A, Farrell M, Delanty N. Progressive myoclonic epilepsies: A review of genetic and therapeutic aspects . Lancet Neurol 2005;4:239-248.

(13.) Verrotti A, Salusti B, Trotta D, et al. Epilepsy evaluation by electroencephalography and magnetoencephalography in Lafora-body disease: A case report. Acta Pediatr 2003;92:1218-1222.

(14.) Wallace R. A second gene for Lafora disease. Epilepsy Curr 2004;4:82-83.

CORRESPONDENCE: Glen A. Palmer, Ph.D., ABPN, Lanning Center for Behavioral Services, 835 South Burlington Avenue, Suite 108, Hastings, NE 68901; tel.: 402-463-7711; fax: 402461-5099; email: gpalmer@mlmh.org.

Glen A. Palmer, Ph.D., ABPN (1) & Forrest H. Mark, M.S., L.P.C., BCBA (2)

(1) Mary Lanning Memorial Hospital, Hastings, NE

(2) Wyoming State Training School, Lander, WY
TABLE 1. CLINICAL FEATURES OF LAFORA DISEASE

1. One type of progressive myoclonic epilepsy
2. Neurometabolic disorder of autosomal recessive inheritance
3. Tonic-clonic and myoclonic seizures most commonly reported
4. Occipital seizures sometimes reported with visual hallucinations
5. Neurological symptoms might include dysarthria, mutism, ataxia,
 paresis, and/or blindness
6. Neurometabolic disorder of autosomal recessive inheritance
7. Linked to the mutation of the EPM2A and/or EPM2B genes of
 chromosome 6. A third gene, yet to be identified, is also suspected
 to cause the disorder.
8. Intellectual disability can be found with Lafora disease; dementia
 occurs during late stages of the disorder.
9. Other mental health concerns include depression, psychosis, and
 personality changes.
10. Lafora bodies can be found in the liver, neurons, skin, heart,
 skeletal muscles, and sweat gland cells.
11. Biopsy of skin cells is usually conducted in order to diagnose
 the disorder.
12. Lafora disease is always fatal.

TABLE 2. PROGRESSION OF COGNITIVE DECLINE AS DESCRIBED BY
INTELLECTUAL FUNCTIONING

AGE INTELLECTUAL ABILITIES

14 85
18 55
22 <40 *

* Estimate of Mr. C's intellectual abilities. He was unable to respond
to stimuli presented on the intelligence measure. Reports of adaptive
behavior were in the profound range.
COPYRIGHT 2007 Psych-Media of North Carolina, Inc.
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2007 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Palmer, Glen A.; Mark, Forrest H.
Publication:Mental Health Aspects of Developmental Disabilities
Article Type:Case study
Geographic Code:1USA
Date:Jan 1, 2007
Words:2778
Previous Article:A case of panic disorder treated with cognitive behavioral therapy techniques.
Next Article:Public systems supports for people with intellectual disability and mental health needs in the United States.
Topics:


Related Articles
Type IV glycogen storage disease. (Images in Pathology).
Smallpox vaccine policy: the national debate. (Health Policy Update).
Diabetic Ketoacidosis in a patient treated with olanzapine, valproic acid, and venlafaxine. (Letters to the Editor).
Physical ailments hamper patients' reintegration: schizophrenia, mood disorders.
Primary care physicians: coordinating mental health care key to better outcomes.
New face of the old foe: central nervous system tuberculosis.

Terms of use | Copyright © 2018 Farlex, Inc. | Feedback | For webmasters