Finding Answers For Baja’s Children With Rare Genetic Disorders

October 14, 2019

BY JAMIE KELLY

In the tiny Padrino Children’s Foundation clinic in Todos Santos, 8-year-old Juan sits in his wheelchair awaiting consultation. Juan works hard to negotiate with uncooperative muscles that challenge every aspect of his daily life. Lifting objects is a struggle for hands that refuse to grip. Yet, more frustrating than the physical limitations is the mystery surrounding Juan’s symptoms. Born with multiple fractures, his doctors suspected “Brittle bone disease” and told his parents, Flor and Juan Diego, that they should not hold their newborn. The diagnosis shifted like sand over the years while the family committed time and money to ineffective therapies and dozens of trips to see specialists in Mexico City and Guadalajara. No one had been able to tell the family what caused Juan’s condition nor offer effective treatment. 

Juan is among the first Mexican patients with rare diseases to receive a diagnosis with from whole-genome sequencing.

Dr. Alejandra Peña Salguero, Padrino Children's Foundation medical director and primary care physician.

In 2017, I was writing an article for Journal de Pacifico discussing the newly formed Padrino Children’s Foundation (PCF) in Todos Santos. While interviewing Dr. Alejandra Peña Salguero, the PCF medical director, she shared how surprising it was to have encountered so many suspected genetic disorders in just a few short years in Southern Baja. And, she lamented that even if a diagnosis were possible for these children, the absence of pediatric specialists limited care options. PCF was the only hope for many children with rare disorders in the state of Baja California Sur, where most genetic tests are not covered by public health services. Within the first year, the foundation was treating more than a dozen children with neurodevelopmental delays and serious medical conditions stemming from unknown causes.

Meanwhile, the San Diego-based biotech company, Illumina Corporation, had launched an initiative called iHope, which included a cross-border genetic testing partnership with San Diego’s Rady Children’s Hospital and the Children’s Hospital of the Californias in Tijuana to identify children with rare genetic disorders and offer WGS for definitive diagnosis. Along the way, they would build the evidence base of known genetic mutations for ongoing medical research. I learned of iHope from my husband, then an employee of Illumina. Within a month, Dr. Peña Salguero was on a plane to participate in a first of its kind genetic clinic in Tijuana. Shortly thereafter, PCF became an iHope partner and the recipient of 15 WGS test kits. We set to work creating plans for our own DNA Day in Todos Santos.

Several local children including Juan were obvious candidates for the test. They had completed preliminary testing to rule out more common disorders, yet the children remained undiagnosed. Through CRIT (Centro de Rehabilitación e Inclusión Infantil Teletón), an organization in La Paz that treats many of our own patients, we found the remaining candidates and identified 15 additional children still in the process of microarray testing. One of our own patients with a rare disease introduced us to Dr. Paola Medina, a highly credentialed neuro-geneticist living in Hermosillo, MX, who became and remains an indispensable member of the PCF team. In a figurative desert of genetic expertise, we found a font of experience flowing with knowledge.

Dr. Paola Medina in consultation with Hassed Castillo and his mother, Jessica Garciglia, one of 37 families that participated in the recent DNA Day genetics clinic in Todos Santos.

Not all genetic disorders are treatable, but many are. Our iHope partner in Tijuana reported that 48.8% of the children diagnosed with WGS had a change in clinical care management as a result of the findings. For example, genetic testing can identify pharmaceuticals that should not be given based on DNA profiles, sparing the family needless expense and the child medication side effects, or even a serious adverse drug reaction. This was an important finding for a child in our first group. When it came time to inform 7-year-old Cristopher’s family of his WGS diagnosis of a collagen disorder, we were unable to locate them. As if by a miracle, Dr. Medina had recently seen him in a hospital 400 miles away in Ciudad Obregon where be was in critical condition awaiting a kidney transplant. A secret revealed in his DNA offered critical information for his medical team in Sonora. The blood thinner, Warfarin, which is commonly used in transplant cases to prevent clotting, could be life-threatening for Cristopher. Having this critical information may have prevented a tragedy.

Considering our diagnostic success, the iHope Project granted PCF 60 additional WGS tests over the next two years. In September, we held our first multi-stage genetics clinic. Doctors Medina and Peña Salguero delivered results to the families of the first 15 children tested. We also welcomed 37 new children into the program: 16 recipients of WGS, 12 future candidates who gave specimens for microarray testing, and 9 children who qualified but have been placed on a waitlist until additional funds can be raised. In the bustle of this busy clinic, my thoughts turned to the karmic forces at play. Two extraordinary clinicians unite in a tiny Baja town, one coincidentally employed spouse, the generosity of an American biotech giant, and 15 families who put their hope in our hands came together to catapult Mexico forward Jeshua Méndez and his father, Porfirio Mendez, take a break during the Padrino Children’s Foundation 2018 DNA Day clinic in partnership with the iHope Project.

But for the parents emerging from the consultation room that day, the future of Mexican healthcare was not top of mind. Flor and Juan Diego emerged having learned that a mutation in their son’s DNA confused the type of fiber that makes up his musculature. With this new information, the family removed Juan from the waiting list to undergo a nerve biopsy, an invasive procedure with a known risk of further deterioration and which could not have diagnosed his condition. While his past physical therapies at CRIT had been cautiously conservative in the absence of a diagnosis, the little boy that began life misdiagnosed and without the comfort of his parents embrace can now receive tailored therapies designed to safely target his specific condition. Ultimately, the end of an odyssey looks like a new beginning.

How can you help? To grow the genetics program, PCF is seeking funds for the microarray testing needed to qualify new children for WGS. If you wish to help with this effort, please go to https://www.padrinocf.org/ and click on the Give or Donate buttons. Questions? Send us a note at info@padrinocf.org.