About

I am a Biochemistry major and Jewish Studies minor (class of 2019) at Muhlenberg College. My Culminating Undergraduate Experience (CUE), Advanced Biochemistry (BCM441), is a course “concerned with the content, presentation and evaluation of modern biochemistry.” In the wise words of Dr. Keri Colabroy, “while studying metabolism, we will investigate applications to human disease and biotechnology, explore current topics in biochemistry, and learn to identify and report on exciting new discoveries within the field. We will reflect on and engage with the process by which biochemistry is practiced and published to the scientific community and to non-expert audiences.”

Follow these steps to make the most of my website!

1. Visit my PRIMER PAGE to learn the background on Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Symptoms (MELAS) and become familiar with the terminology

2. Read my POST for scientists and non-experts summarizing this disease

3. Check out the THEME PAGES to investigate MELAS from a biochemist’s lens (me!)

RETURN TO HOME: http://alyssadhorwitz.bergbuilds.domains/

2 thoughts on “About

  1. Hi there! I have a few questions about MELAS for you if you can answer them.

    You mentioned the ability for genetic screening in suspected MELAS cases based on the MRM2 gene. What do you think about screening in the general population? What would be the cost-benefit of this screening? Additionally, if we were to screen children with a family history of MELAS, how would a positive result change management of their health and development?

    You stated the components of Cardiocrome, and it sounds like an interesting medication. What other disorders are Cardiocrome used to treat, if any, and how are they similar/dissimilar to MELAS?

    Lastly, you mentioned the study of two sisters with MELAS. Have you come across the probability of siblings or twins sharing a diagnosis of MELAS?

    1. Hello! Thank you for the questions!

      The diagnosis of MELAS is based on meeting clinical diagnostic criteria and identifying a pathogenic mutation in at least one of the genes associated with MELAS. The cost for a custom genetic panel is around $1,500, so it would likely only be used in the case of confirming a diagnosis. Treatment of MELAS is largely supportive, and with the absence of genetic therapies, at this point in time, a positive result would not change the management of a patient’s health (El-Hattab, Almannai, and Scaglia 1993).

      Cardiome contains cytochrome c, flavin mononucleotide, and thiamine diphosphate. In addition to MELAS, it can be used to treat Kearns-Sayre syndrome (KSS), myoclonus epilepsy with ragged-red fibers (MERRF) and cytochrome c oxidase deficiency (CCOD). (Tanaka et al. 1997) This treatment increases the effectiveness of the electron transport chain of the inner mitochondrial membrane and relieves oxidative stress, consequently protecting cells or tissues from apoptotic cell death. This drug must be administered intravenously because the oral version is not sufficient for delivery.
      There are many case studies reported about familial MELAS. Most notably, one compared two pairs of male twins (monozygotic) with the mitochondrial 3243 A>G mutation and a MELAS phenotype. For the pairs of twins, the clinical phenotype and segregation of 3243A>G mutation among tissues were similar. The results indicate that the clinical phenotype of this mutation and the tissue distribution of the mutation do not occur by chance but are predetermined. This is common in hereditary diseases resulting from nuclear gene abnormalities. (Maeda et al. 2016).
      In another report, an entire family demonstrated the clinical and pathological features of the patient who was finally diagnosed with MELAS and diabetes. The mtDNA mutations were present in the whole family (Li et al. 2015). Maternal mitochondrial inheritance is associated with a significant degree of variability. Mothers of individuals with MELAS usually have the mtDNA mutation, and thus all siblings of the individual with MELAS also have the mtDNA mutation.
      In one large MELAS pedigree, 26 out of 27 living family members were m.3243A > G mutation positive. Eighteen were symptomatic m.3243A > G mutation carriers without traditionally recognized stroke-like episodes were diagnosed with diabetes, nephropathy, mild myopathy, cardiomyopathy, sensorineural hearing loss, cerebellar disease, and mental retardation. Eight m.3243A > G mutation carriers in this pedigree were asymptomatic demonstrating incomplete penetrance sometimes observed among mutation carriers (Ikeda et al. 2018).

      Hope this was helpful!

      References:

      El-Hattab, Ayman W., Mohammed Almannai, and Fernando Scaglia. 1993. “MELAS.” In GeneReviews®, edited by Margaret P. Adam, Holly H. Ardinger, Roberta A. Pagon, Stephanie E. Wallace, Lora JH Bean, Karen Stephens, and Anne Amemiya. Seattle (WA): University of Washington, Seattle. http://www.ncbi.nlm.nih.gov/books/NBK1233/.

      Ikeda, Takahiro, Hitoshi Osaka, Hiroko Shimbo, Makiko Tajika, Masayo Yamazaki, Ayako Ueda, Kei Murayama, and Takanori Yamagata. 2018. “Mitochondrial DNA 3243A>T Mutation in a Patient with MELAS Syndrome.” Report. Nature Publishing Group. https://doi.org/10.1038/s41439-018-0026-6.

      Li, Weiwei, Wei Zhang, Fang Li, and Cailing Wang. 2015. “Mitochondrial Genetic Analysis in a Chinese Family Suffering from Both Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes and Diabetes.” International Journal of Clinical and Experimental Pathology 8 (6): 7022–27.

      Maeda, Kengo, Hiromichi Kawai, Mitsuru Sanada, Tomoya Terashima, Nobuhiro Ogawa, Ryo Idehara, Tetsuya Makiishi, et al. 2016. “Clinical Phenotype and Segregation of Mitochondrial 3243A>G Mutation in 2 Pairs of Monozygotic Twins.” JAMA Neurology 73 (8): 990–93. https://doi.org/10.1001/jamaneurol.2016.0886.

      Tanaka, Junko, Toshisaburo Nagai, Hiroshi Arai, Koji Inui, Hideo Yamanouchi, Yu-ichi Goto, Ikuya Nonaka, and Shintaro Okada. 1997. “Treatment of Mitochondrial Encephalomyopathy with a Combination of Cytochrome C and Vitamins B1 and B2.” Brain and Development 19 (4): 262–67. https://doi.org/10.1016/S0387-7604(97)00573-1.

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