Last June, when 2-year-old Matthew Ouimet of Antioch, Calif., underwent transplant surgery for his kidneys and liver, Californians followed the story closely, rooting for this little boy and his family.
Because of Matthew, who faces a long, bumpy road to recovery, many people have now become aware of a little-known medical condition, primary hyperoxaluria (PH) Type I, a rare metabolic genetic disease that strikes only one to three people in a million worldwide. The disease primarily affects the kidneys, but it can affect other organs if left untreated.
PH causes the liver to excrete too much oxalate, which combines with calcium to form calcium oxalate crystals that can damage the kidneys and cause kidney stones.
Like most Americans, and even many American physicians who specialize in metabolic diseases, Lori Magaziner, a native Baltimorean who now lives in Phoenix, Ariz., with her almost 2-year-old daughter, Miryam, and Miryam’s father, Jake, had never heard of PH. So when Miryam developed a urinary tract infection (UTI) at 6 months old, she wasn’t expecting her daughter to require a five-day hospital stay. Six months later, Miryam had another UTI, and — standard practice after a baby has two UTIs — she was tested for vesicoureteral reflux, a relatively common condition, where the flow of urine pushes back into the urethra. When the results came back, Magaziner was told that Miryam had a diagnosis of vesicoureteral reflux as well as a 7-millimeter mass on her kidney. She was referred to a urologist, who determined that Miryam needed an MRI and X-rays. This was the beginning of what would be the most overwhelming and frustrating time in the family’s life.
The mass turned out to be a large kidney stone, but it was precariously located, and there were still many unanswered questions.
Miryam, who was receiving treatment from the chief of pediatric nephrology at the Phoenix Children’s Hospital, was given a lithotripsy to break up the large kidney stone and underwent a battery of inconclusive tests. Six months later, Miryam still had no diagnosis. In a desperate search for answers, Magaziner finally stumbled upon the Oxalosis & Hyperoxaluria Foundation (OHF) website. She and Miryam’s nephrologist contacted the foundation and were put in touch with the OHF-sponsored Mayo Clinic Hyperoxaluria Center and its director, Dr. Dawn Milliner.
Dr. Milliner said the center has been studying and treating the disease, now known to have at least three recognized types of varying severity, for more than 40 years. Type I, the most serious form, affects approximately 75 percent of those with PH, Types II and III (less serious forms) affect approximately 8 to 10 percent. “Other” PH patients comprise about 6 to 8 percent.
“The Mayo Clinic maintains an international registry of patients with hyperoxaluria, so we can learn about patients all over the world,” said Dr. Milliner. The registry, sponsored by the National Institutes of Health (NIH), allows health-care providers to input information about their patients so they can learn from one another and gain a more comprehensive
understanding of PH.
“These diseases are inherited in a recessive pattern; that is, each parent must have a copy of the mutated gene, although both appear healthy. There is a change in the DNA sequence, but it is different in each type of hyperoxaluria,” explained Dr. Milliner. “When these mutations are present … too much oxalate is produced. If the kidneys work well, they get rid of it, but over time, the high oxalate levels cause kidney stones and later damage the kidneys. Most often, it is a kidney stone in a child that raises suspicions and brings the disease to medical attention.”
Although patients are born with PH, some who have the disease are not diagnosed until their 30s or even 60s. Sometimes, it is not diagnosed until kidney failure.
Dr. Milliner said she and her colleagues are trying to raise awareness about PH so it can be treated early and complications can be avoided.
“There’s a lot that can be done to minimize the formation of crystals, reduce the number of kidney stones and to prevent kidney damage. Even when serious kidney complications occur, there are effective treatments,” said Dr. Milliner.
The doctor noted that there are safe medications that treat the three recognized types of PH. Patients with the disease require high quantities of fluids and must take medications every day.
Dr. Milliner believes there are likely at least several other types of PH that are not yet defined. Research is important, she said.
“Despite the problems caused by this disease, advances in understanding PH, availability of early diagnosis and improvements in care mean patients can live full and productive lives and provide hope for the future,” said Dr. Milliner.
In February 2013, Dr. Milliner diagnosed Miryam with Type III PH, the mildest and the most recently identified form of the disease. To learn more about Type III, Magaziner consulted with Dr. Yaacov Frishberg, director of the Division of Pediatric Nephrology at Shaare Zedek Medical Center in Jerusalem. Dr. Frishberg is credited with discovering PH Type III in 2010. The doctor’s clinical experiences led to his assumption that Type III was a genetic disease prevalent among Ashkenazi Jews. Subsequent research resulted in the identification of a particular genetic mutation responsible for this new clinical entity. Because it is a hereditary disease, siblings of children with PH are also tested for the mutation. In one case, Dr. Frishberg found five out of 10 children in an Ashkenazi family all had PH III. However, at the time of testing, only two of the siblings had formed kidney stones.
Now that Magaziner better understands Miryam’s condition, she said feels more comfortable handling her daughter’s care.
“She’s passed 12 stones this year. We know this through ultrasounds. She only showed some transient pain with a couple of them,” said Magaziner.
Miryam must have ultrasounds every three months and blood work every two months. Her potassium levels are also tested on a regular basis.
“A huge part of her treatment is her fluid intake. Miryam drinks between 38 and 50 ounces of fluid a day,” said Magaziner.
Additionally, Miryam will always need to contend with her body’s tendency to form stones. Some of the stones will pass without intervention, but others will require surgery.
Despite all she’s been through, Magaziner said Miryam is always smiling.
“They [doctors] can’t say with 100 percent certainty that she’ll never have kidney problems, but so far there are no cases of children with Type III who have undergone renal failure,” said Magaziner.
Magaziner said she hopes her family’s story will help others who may be undiagnosed to find the care they need. She encouraged parents or adults with unexplained kidney stones to be proactive.
“You must be your own advocate,” she said.
Simone Ellin is JT senior features reporter — email@example.com