Fanconi Fun

 Reuben yesterday with my birthday "cupcake on ice cream!"

I wrote this rather slapdash report last week for my Coursera Chemistry mini research paper. If you've been interested in Reuben's kidney disease, well, THIS TREAT IS FOR YOU.

My five year old son Reuben has Fanconi syndrome, diagnosed during a period of poor growth after chemotherapy treatment for a synovial sarcoma in his right shoulder. Fanconi syndrome is a kidney disorder caused by damage to the proximal tubules in the kidney, in his case from therapeutic use of the drug ifosfamide [2,3]. The result is a diminished reabsorption of solutes by the proximal tubule. Clinical manifestations of this disorder can be more complex, depending on the biological cause of the tubule damage, but in Reuben's case his symptoms and management are limited to nutritional electrolyte levels and prevention of acidosis. [1,2]

Reuben was promptly treated with heavy supplementation of electrolytes and bicarbonate, and avoided the side effects (rickets from phosphorus and vitamin D deficiency is one concern) that could be caused by nutritional deficiency of essential electrolytes [3]. This treatment has continued for four years. More advanced biochemistry can be applied to the mechanisms of his renal tubules and the biological effects of these electrolytes, but I will limit this brief discussion to inorganic chemistry. As we learned about electrolytic reactions and precipitates in Week 4, I immediately thought of the precipitates I have observed in Reuben's urine. "Tell your doctor about cloudy urine" urge parenting articles, so I asked his nephrologist, who has assured me (from theoretical knowledge and the urinalysis done regularly) that the cloudiness in the toilet bowl, what I saw crystalized at the bottom of his wee toilet during potty training, and the residue I sometimes observe in his underwear is expected. I'm seeing a solid result of most of  the electrolyte solution I deliver three times daily orally, processed inefficiently by his damaged kidneys ("It's chemistry in action!" I told my physician and biologist siblings. Our inner chemistry geeks were very excited). This paper--and the refreshing of my 20-year-dormant inorganic chemistry skills with this class--gives me the opportunity to make a prediction exactly what the precipitates are.

I theoretically know that Reuben likely has excessive urination of many solutes, including glucose, amino acids, calcium, phosphate, uric acid, bicarbonate and many organic compounds [3]. I can reasonably conclude, however, that he is excreting most what he receives most of. His daily oral supplementation regimen gives him the following, which represents a massive excess of what his little 43 pound body uses: 

*30 mL of CYTRA-2, a formulation that includes sodium citrate and citric acid in a neutralizing buffer. For the purposes of this paper, I'm going to ignore the inactive ingredients, and just consider the stated concentrations in 5 mL aqueous solution: 500 mg Sodium Citrate Dihydrate and 334 mg Citric Acid Monohydrate. The label states that each mL contains 1 mEq Sodium Ion and is equivalent to 1 mEq Bicarbonate (HCO3) [4].

*1 1/2 packets of PHOS-NaK, a powdered concentrate. Each packet contains (again, just the active ingredients) 160 mg sodium, 280 mg potassium, and 250 mg phosphorus in the form of potassium phosphate and sodium phosphate.

Calculations:

part 1: the ions

From CYTRA-2: Na+, HCO3 -2  (the sodium citrate and citric acid in the CYTRA-2 are converted to bicarbonate by the liver [7]).

From Phos-NaK: K+, Na+, PO4 -3 (phosphorus is transported and processed in the intestine, kidneys, and urine in phosphate form [8]).

Resultant cations: Na+,  K+

Resultant anions: HCO3 -2, PO4 -3

part 2: the precipitates 

I expected to discover in this step that one of the resultant ionic compounds was insoluble, and that would be the precipitate that I observe, but according to solubility rule #1, "Most compounds of Group 1 metal cations are soluble." Because both of the supplemental cations are Group 1 metals, I can expect that the possible compounds of the ions listed above would be primarily in solution. The precipitate I observe must therefore be the result of an already fully saturated aqueous solution in Reuben's urine. I predict the following possible electrolyte salts in excess: Na2HCO3, K2HCO3, Na3PO4, K3PO4 (sodium bicarbonate, potassium bicarbonate, sodium phosphate, and potassium phosphate).

If this chapter of my education extends to a laboratory portion of my chemistry review, I may, in the future, be able to test the accuracy of the predictions made by my chemical figuring above. I could do further research on the way the digestive system uses and transforms elements and their ions to be more accurate in my chemical predictions, but the above exercise was interesting, and appropriate at my current chemistry knowledge level. "Fanconi syndrome" describes a class of disorders whose variable symptoms depend on the cause and extent of the proximal tubule damage [2]. I would like to know exactly what Reuben's body disposes of, and how this changes as his body and metabolic needs grow. More specific research could still be done on the chemistry of affected patients' urine and blood to see exactly the sort of damage done to a 6 month old child with high doses of ifosfamide (it was reported as early as 1974 [3,6]), but I hope that the incidence of cases remain low enough that such studies cannot be categorically conclusive, particularly at stages of early development, such as my 6-month old baby. 

Sources cited:

1. "Fanconi Syndrome." Author: Sahar Fathallah-Shaykh, MD; Chief Editor: Craig B Langman, MD. Accessed on web at http://emedicine.medscape.com/article/981774-overview.

2. Discussions with the subject's mother and nephrologists.

3. " Ifosfamide induced Fanconi syndrome." Samantha Buttemer, Mohan Pai2 and Keith K Lau. BMJ Case Rep. 2011; 2011.  Accessed on web at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246161/

4. Label for Cypress Pharmaceutical, Inc.'s CYTRA-2 oral solution.

5. Label for Cypress Pharmaceutical, Inc.'s PHOS-NaK powder concentrate supplements.

6. "Renal dysfunction after treatment with isophosphamide." DeFronzo RA, Abeloff M, Braine H, Humphrey RL, Davis PJ. Cancer Chemother Rep. 1974 May-Jun;58(3):375-82. Accessed on web at http://www.ncbi.nlm.nih.gov/pubmed/4842666.
7. "Urinary Alkalization" by David S Goldfarb, M.D.(Director, Kidney Stone Prevention Program, St. Vincents Hospital & Professor of Medicine and Physiology, NYU School of Medicine). Accessed on web at http://www.cystinuria.com/articles/urinary-alkalization/.

8. "Potassium Phosphate/Pharmacology." Accessed on the web at http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=516951#x94

Educational Trip

Self + sibs: a blurry attempt to recreate a favorite 2002 photo, the last time we were all together for my mom's 60th a couple of years ago

Today's morning task: Educational Trip Form Request for both daughters, seeking excused absence status when missing school around Easter for a trip to join this bunch, my mom (Grandma Donna the Grand Madonna), plus so many spouses and kids.

"Please write a short summary of the educational value of the planned trip"

I'm not going to try to make a case for the April entertainment pursuits in Orlando being essential to my girls' education, but I firmly believe that the company is. This is the first biannual reunion of my family of origin, seven siblings and their mum spread between seven states, so also my kids' only chance to spend time with, appreciated and loved and taught by their best educational mentors. We'll have fourteen bachelor's degrees, two master's, and four doctorates, with one just starting medical school and another three years into an evolutionary biostatistics entomology PhD program. There will be three professors, two practicing physicians, one scrupulous dentist, and a successful entrepreneur in our little group, all people (along with the also brilliant rest) with senses of wonder to match their senses of humor, a week-long interactive lesson on how education makes minds sharp, parenting fuller, and lives better. Value indeed!

a love story

A year and a half since I've posted on this neglected blog! This story, too long for the replacement Facebook, needed to be told.

Thursday night before bookclub, Goat and I attended the funeral of Evelyn Gilmartin, a member of our church. Neither of us had interacted past the "good morning" level with Sister Gilmartin, whose poor health often kept her home, but we went in support of her widower, Frankie, an iconic presence every Sunday.  Frankie passes out the programs, reaches past three or four people to adjust your hymnal if you put it away "wrong" (it's firm tradition in our particular congregation--something I've never seen before--that hymnals must be put in place spine down; they're even stamped "this side up" along the outer margin), and is always prompt with his after-meeting task of wheeling in the chalkboard for the Sunday School class that meets in the chapel after our main devotional services. Frankie will need the support of his church without Evelyn. She was quiet but bright, efficient with her church calling (sending the women's organization e-newsletter), and definitely took care of the adult world for their household. Frankie, officious but kind, has the mind of a child. He's difficult to understand, and will not be able to live on his own without her. Their marriage was a happy mystery to us.

The glowing spot in the simple service was their love story. When we arrived and stopped to sign the guest book, Evelyn's sister Jessie was setting out a few items to represent her sister--the bracelets she enjoyed making, a small sampling of her proudly complete Dark Shadows collection, family photos, and a plain black-and-white dollar store composition book. "She wrote the things she wasn't able to say." Jessie's husband gave the eulogy, with both his words and a written memorial from his wife, who was feeling too emotional to speak. He explained that the Gilmartins' marriage was Evelyn's third. Her first husband was physically abusive, and her second "had plenty of issues of his own." When she met Frankie while living for a time with a friend in Florida, she was in another abusive relationship, which he, entranced by Evelyn, stepped into. Frankie spent half of his few words at the service describing their beginning: "I said to him, 'If you want to hit her, you're going to have to get past ME FIRST.'" Jessie said of Frankie, "He treated her like a queen." 

Jessie asked Mary Ellen Moore, a friend of Evelyn, to read a poem from that composition book I saw on entrance. It is titled simply "To Frankie", and was written four years ago. He had never heard it.

Thank you for being a part of my life;

for being my partner and friend;

for sharing my life, the good and the bad,

through all of the thick and thin.

Thank you for being my anchor,

for your shoulder whenever I cried;

for being that one special someone,

in whom I can always confide,

for staying when I'm at my worst, 

and praising when I'm at my best;

for listening quietly to me,

when I have things to get off of my chest.

Thank you for not criticizing, 

or pointing out all of my flaws;

for being supportive and caring, 

and loving me just because.

Thank you for not ever hitting, 

but helping wherever you can;

and when I am struggling and falling,

for offering me your hand.

For being my strength and my guidepost,

my joy and the love of my life;

Thank you for all that you've given, 

and especially for making me your wife.

For all that you are, for all that you give,

for all you have helped me to be;

for all of the people to choose from,

I thank you for choosing me.

I love you my darling Frankie,

you're my heart, my soul and my life.

In all of the things I could have done,

I'm proudest that I am your wife.

I love you!

My favorite moment of the evening was watching Frankie mouth clearly to his sister-in-law, sitting closely and protectively nearby, "She wrote that for ME?" A breathtaking gift for a heartbroken new widower.

The Gilmartins' kindness to each other continued for the rest of their twenty-year marriage. A dear friend's marriage hit a move-out-and-begin-again crisis this week, which has led me to think a lot about my own. My marriage moanings are usually of the "we don't have the same goals" variety [fear not, reader: we mostly do, veering sharply at leisure time activities]. Frankie and Evelyn's love story is a beautiful example of the right marriage goals: unfailing support, the audacity of love in the face of difference, and the eminence of kindness in every relationship. May we all be so lucky and so wise.

 A memorial with a beautiful lesson--please share it in honor of Evelyn and Frankie Gilmartin and L-O-V-E (it's still February, after all!)

A happy portrait of Frankie and Evelyn Gilmartin. The photo to the right is on their sealing day in the Washington, D.C. temple.