Friday, March 1

Health - Lysosomal storage disorders

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Nutrition, Health & Wellness

Lysosomal storage disorders
May 2013
Home > Lysosomal storage diseases
Lysosomal storage disorders (LSDs) are a large heterogeneous group of more than fifty genetically inherited metabolic disorders characterized by lysosomal malfunctions in body's cells. Most of them are rare types caused by autosomal recessive inheritance. However, a few are X-linked and recessive.

Though known as pediatric disorders, late on-setting adult forms have been recognized. Certain ethnic groups have an increased carrier frequency for specific disorders. Pompe, Gaucher, Niemann-Pick, Tay-Sachs, Sandhoff, Krabbe, Hermansky-Pudlak, Chediak-Higashi, Griscelli and Fabry disorders are the more known conditions.

What is lysosomal storage disorder?

The lysosomal body is a specialized organelle in the cell which by enzymatic activity breaks down and recycles unwanted materials in the cell. In certain inherited disorders resulting from different gene mutations, there is deficiency or absence of the lysosomal enzyme activity leading to storage and accumulation of substances destined for breakdown and recycling. The supposition of these disorders has been broadened to include deficiency, absence or defect in certain crucial proteins. These proteins are required for post-translational modifications, activator functions and intracellular trafficking between the lysosomal body and other intracellular components.

Classification of lysosomal storage disorders

Considering the type of defect in degradation on molecular basis, lysosomal storage disorders are classified as follows:
  • non-enzymatic lysosomal protein defects,
  • transporters and structural proteins defects,
  • lysosomal enzyme protection defects,
  • post-translational processing defects,
  • neuronal ceroid lipofuscinoses (NCLs),
  • polypeptide degradation defects and
  • defects in lysosomal trafficking. 

Symptoms and manifestations

These storage disorders vary in degree of intensity in respect to the type of afflicting disorder and the age of onset. Moreover, the clinical manifestations of a particular type may vary widely among the affected patients. In severe forms of the disorder there may be total debility and even death. In untreated cases, there is gradual progressive increase in the intensity of symptoms and morbidity.

The clinical manifestations of lysosomal storage disorders are:
  • developmental delay, 
  • impaired mobility, 
  • ataxia and hypotonia, 
  • spasticity and hypertonia, 
  • convulsions and seizures, 
  • peripheral neuropathy, 
  • impaired vision and hearing, 
  • corneal clouding, 
  • enlargement of the liver, spleen and heart, 
  • lung and heart disorders, 
  • bone abnormalities, 
  • dementia and intellectual disability and
  • neuromuscular disorders.

Testing, screening and diagnosis

If a patient has one or more of the symptoms, tests may be conducted to rule out lysosomal storage disorder. To arrive at a definitive diagnosis enzyme assay and enzymatic activity measurement is done. Skeletal radiography is performed to find evidence of bone and cartilage malformations. Ultrasonography is performed to identify cardiomegaly, splenomegaly and hepatomegaly. To find evidence of cardiac involvement, echocardiography is performed. Ophthalmologic, hearing and ear Screening are performed to find evidence of lysosomal storage disorders. Peripheral blood smear test may be carried out to look for presence of anomalies in white blood cell vacuoles. Urine is tested for increased presence of oligosaccharides and glycosaminoglycans. Molecular analysis and molecular genetic testing (MGT), though rarely used, helps in carrier and prenatal testing.

Treatment trends

Recent research efforts have opened up many new therapeutic possibilities and options like enzyme replacement therapy, hematopoietic stem cell transplantation, substrate reduction therapy and molecular chaperone therapy.

Enzyme replacement therapy (ERT)

Enzyme replacement therapy has been found to be safe and promising. However, for central nervous system manifestations ERT has been largely ineffective. To overcome the difficulty in penetrating the blood-brain barrier, active clinical trials are evaluating the efficacy of intrathecal enzyme delivery.

Hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation with bone marrow or umbilical cord blood cells have been found to be effective in preventing the progression when performed early in the course of the disorder. Combination  therapy with hematopoietic stem cell transplantation and ERT has been found to be superior in results compared to separate treatments.

Substrate reduction therapy

Experiments and trials are going on substrate reduction therapy process to reduce the accumulated storage material. Substrate storage reduction therapy addresses the failure of the metabolic pathway and the accumulation of the substrate. If the level of substrate storage is reduced, the residual degradative activity may be sufficient to reduce and prevent substrate accumulation and storage.

Molecular chaperone therapy

One of the latest pharmacological process in the treatment of lysosomal storage disorder is molecular chaperone therapy. Chaperones are minute molecules which can penetrate blood brain barrier. Once the chaperones enter the central nervous system, they attach to the defective enzyme to make it functional. There are some limitations to molecular chaperone therapy as it is effective only in certain of the disorders. Research and clinical trials are currently going on to improve the efficacy and dosage management of molecular chaperone therapy for the treatment of this storage disorder.

1.Mirella Filocamo and Amelia Morrone. Lysosomal storage disorders: Molecular basis and laboratory testing. Hum Genomics. 2011 Mar;5(3):156-69.
2.Orna Staretz-Chacham, MD, Tess C. Lang, BS, Mary E. LaMarca, BA, Donna Krasnewich, MD, PhD, Ellen Sidransky, MD. Lysosomal Storage Disorders in the Newborn. Pediatrics. 2009 April; 123(4): 1191–1207.
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Monday, January 28

Fitness - Loneliness and health - Loneliness in elderly

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Loneliness and elderly health Home > Loneliness and health - Loneliness in the elderly
Loneliness among elderly people has been connected to poor health, higher morbidity and mortality. Such feeling in the elderly may raise the potential for certain health risks including depression, suicidal tendency, increased stress, decreased memory, altered brain function, depressed immunity, high blood pressure and heart disease.

The meaning of loneliness

Loneliness may be defined as a lasting emotional state of estrangement, a feeling of being misunderstood, a feeling of rejection by others and lack of social partners for desired activities. This feeling often occurs in adolescents and aged people. However it is transient in adolescents. In elderly, it can lead to social isolation and reduced contacts with other people.

Loneliness and health of elderly

In the news release "Loneliness Linked to Serious Health Problems and Death Among Elderly" on June 18, 2012, Leland Kim (Senior Public Information Representative of University of California, San Francisco) informed that

"Loneliness — the unpleasant feeling of emptiness or desolation — can creep in and cause suffering to people at any age. But it can be especially debilitating to elderly and may predict serious health problems and even death, according to a new study by UCSF researchers ( Carla Perissinotto, MD, MHS et al)." The study found that only 18% persons above sixty years lived on their own. 43% of the elderly people surveyed suffered from loneliness. The study concluded that among the participants who were older than 60 years, it was a predictor of functional decline and death.

Regarding the health of people living in isolation, Michelle Mitchell, Charity Director General of Age UK said: "Living in isolation and loneliness is a stark reality for too many people in later life, and feelings of loneliness can have a significantly adverse effect on physical and mental well-being."

Causes of loneliness

Death of a life partner or a close friend, lack of companionship, chronic illness and lack of friends are the most common causes of seclusion. Lack of companionship and emotional support can cause elderly to internalize negative feelings which can compound the sense of isolation and affect their health. This feeling can affect both, mental and physical condition of the elderly people.
There is a well-established relationship between loneliness and aging. Natural aging process brings about a number of changes in a person. Decreased functional ability and efficiency impacts the health. The following aging related afflictions cause poor self-rating of health and seclusion:
  • Decreased cardiac output
  • Diminishing ability to respond to stress
  • Loss of bone density
  • Loss of muscle strength and size
  • Decreased lung capacity
  • Decreased gas exchange
  • Degenerative diseases of joints
  • Increased response time to stimuli
  • Impaired vision
  • Impaired hearing
  • Cognitive decline
  • Cognitive impairment
  • Sleep disturbances
  • Higher fatigue levels
  • Decline of functional ability
  • Reduced cerebral circulation affecting balance.

Coping with loneliness

With higher longevity coupled with reduced birth rates, the proportion of aged people in the population is increasing throughout the world. Immediate nationwide measures are required to reduce seclusion and isolation. Loneliness can be alleviated to a certain extent by activities, like reading, gardening, handcraft, light housework, television watching, keeping pets, attending social gathering or taking part in voluntary work.

Support from family and friends, regular contact with family, family involvement in their care and deep, engaging communication between the family members have immense positive effects in coping with loneliness. Forming groups to check the status of health of the elderly in the communities and neighborhood and involving young people in their care can go a long way towards mitigating their health problems and loneliness.

1. Leland Kim on June 18, 2012. Loneliness Linked to Serious Health Problems and Death Among Elderly.
2. Archana Singh and Nishi Misra. Loneliness, depression and sociability in old age. Ind Psychiatry J. 2009 Jan-Jun; 18(1): 51–55.
3. Age UK. Published on 28 September 2012 12:01 AM.

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Author: Thomas Bjørkan
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