AAA Syndrome

Chris Piel
PSY 240 Spring 2013

Alacrima
An inability to secrete tears.

Achalasia
An inability of smooth muscle to move food properly down the esophagus

Addisons disease
Poor adrenal functioning causes low levels of cortisol hormone, crucial to metabolism

Background

Triple A syndrome is actually three diseases: Achalasia, Addisons disease and Alcarima. Each disesease occurs independently of each the other, meaning one does not cause the other. Achalasia: Improper esophagus functioning Addisons disease: Improper functioning of adrenal glands Alcarima: Inability to secrete tears. Also known as Allgrove Syndrome -- discovered by Dr. Jeremy Allgrove in 1978. Its an incredibly rare, genetic disease that can be managed.

AAAS Address: 12q13*

Genetic Causes

High Level: Dysautonomia, dysfunction of the automatic nervous system, which controls involuntary processes such as digestion, blood pressure, sweating, and other processes. There are no known environmental causes of Triple A disease. It is a genetic condition that worsens with time. Autosomal, AAAS Gene mutations causes disease What we know: AAAS gene controls ALADIN protein production. ALADIN is located in the nuclear envelope. It is dysfunctional in Triple A patients.

Scientists believe: ALADIN helps DNA-repairer-molecules (particularly crucial to nervoussystem-cells) enter the cell nucleus. Consequently, DNA mutations during cell division go uncorrected and patients cell function and health deteriorate over time.

*Right next to where genes controlling keratin (skin protein) production are. A major symptom is the darkening of a patients skin. Do you think the genes location causes this symptom?

Number of Cases
Incredibly few. Unknown, very few reports exist. It likely goes undiagnosed in the majority of cases (Ferry, 2013; Chaurasiya, 2010).

Symptoms: Early Development

Infants Alcarima -- an inability to secrete tears, is the first sign in infants. Childhood/Adolescence: Achalasia -- improper esophagus functioning causes severe feeding difficulties such as an inability to swallow, vomiting, and hyperglycemia Addisons disease -- improper adrenal gland production of cortisol hormone leads to fatigue, loss of appetite, weight loss, low blood pressure, and darkening of the skin. Sometimes: Microcephaly/Small Head Developmental delay, intellectual disability Because the condition worsens with time, young children often go undiagnosed until adolescence or adulthood. Proper diagnosis often occurs after a severe hyperglycemic seizure.

*Which/when symptoms appear can vary greatly between patients* Why? Because the disease depends on the type & frequency of DNA mutations. 2-minute synopsis: Addisons disease (YouTube)

Symptoms: Late Development

Adulthood -- when neurological problems become very apparent because conditions have worsened over time. Symptoms can vary greatly, therefore a large combination usually leads to adult diagnosis.

Abnormal sweating Difficulty regulating blood pressure Unequal pupil size (anisocoria), Speech problems (dysarthria) Muscle weakness

Movement problems; nerve abnormalities in extremities (peripheral neuropathy). Less common -- but still important

Thickening of the outer layer of skin (hyperkeratosis) on the palms of their hands and the soles of their feet, other skin abnormalities. Optic atrophy (atrophy of the nerves that carry information from the eyes to the brain) is less common.

Treatments
There are currently no treatments for the cause (faulty ALADIN proteins) of AAA syndrome. Therefore each A is treated individually. Addison disease Regular cortisol hormone medication promotes normal metabolism, normal growth in children, and prevents adrenal crisis. This is the most crucial treatment because cortisol is key to proper metabolism and many basic functions. Achalasia Best treated with surgery to correct structural deformities, then with acid therapies if problems persist. Eat soft foods if surgery is not an option. Alacrima Treat with eye drops.

Lifespan Expectancy
With early diagnosis and proper treatment, patients can have a normal lifespan. Primary cause of death among treated patients is an unexpected adrenal crisis which, due to a shortness of cortisol hormones can cause seizures, coma or shock.

Biological Domain

When AAA Syndrome goes untreated it can cause development delay (undersized, mild retardation) in children and adolescents due to hormone and nutritional deficiencies. Specifically...

Insufficient cortisol causes complications in metabolism (Addisons) An inability to properly swallow food can cause malnourishment (Achalasia)

With treatment, children can develop normally.

Cognitive Domain

Can cause mild retardation due to nutritional and hormonal deficiencies. This is extremely rare and only occurs in untreated severe cases. This is more likely to occur with victims in rural, undeveloped societies, where modern medical attention is not available.

Social & Emotional Domain

In uncomplicated cases, has no unique impact on the social and emotional development of an individual, other than the stresses and strains caused by all forms of illness. If complications cause severe developmental delays or mild mental retardation than social and emotional impacts could potentially be high.

Jill
Jill is a young video blogger who was diagnosed with Addisons disease in adolescence. Addisons is the disease within AAA syndrome that normally has the biggest impact on a patients life. Watch her discuss growing up with it (YouTube)

References
Brooks, B.P., Kleta, R., Stuart, C., Tuchman, M., Jeong, A., Stergiopoulous, S.G.,Bei, T., Bjornson, B., Russell, L., Chanoine, J.P., Tsagarakis, S., Kaisner, L., Stratakis, C. (2005). Genotypic heterogeneity and clinical phenotype in triple A syndrome: a review of the NIH experience 2000-2005. Clinical Genetics, 68 (3): 215. Retrieved: http://openurl.ebscohost.com/linksvc/select.aspx? genre=article&sid=PubMed&issn=00099163&title=Clinical +Genetics&volume=68&issue=3&spage=215&atitle=Genotypic+heterogeneity+and+clinical+phenotype +in+triple+A+syndrome%3a+a+review+of+the+NIH+experience+2000-2005.&aulast=Brooks +BP&date=2005--&isbn=00099163 Chaurasiya, O.S., Kumar, L., & Nagapoonam, M.P. (2010). Allgrove Syndrome. Current Pediatric Research, 14 (2): 89-91. Retrieved from http://www.pediatricresearch.info/yahoo_site_admin/assets/ docs/5.176180525.pdf Ferry, R.J. (2013). Allgrove (AAA) Syndrome. In Medscape Reference. Retrieved from http:// emedicine.medscape.com/article/919360-overview Addisons Disease. (2012). In National Institute of Healths Medline Plus. Retrieved from http:// www.nlm.nih.gov/medlineplus/ency/article/000378.htm Triple A Syndrome. (2010). In U.S. National Library of Medicines Genetics Home Reference. Retrieved from http://ghr.nlm.nih.gov/condition/triple-a-syndrome