Mindy Nicholas – Phenylketonuria (PKU)

At birth Mindy Nicholas appeared to be a normal, healthy baby. But a routine blood screening administered to every newborn revealed she had phenylketonuria (PKU). It’s a metabolic disorder that prevents the body from breaking down proteins.

Three decades later, Mindy is married and living a normal life, free of the highly restrictive diet required of PKU patients. It’s all thanks to the efforts of rare disease doctors, researchers, and transplant surgeons at UPMC Children’s Hospital of Pittsburgh.

PKU is a rare inherited disorder caused when a defective gene is passed on by both parents. The disease leaves the body unable to break down an amino acid called phenylalanine, an essential building block in protein. Phenylalanine is found in breast milk, many types of baby formulas, and most foods, especially those high in protein such as meat, eggs, and dairy. It is even present in some plant-based foods.

When a person with PKU eats foods containing protein, phenylalanine builds up in the bloodstream. Untreated, it can lead to developmental delays, irritability, behavior problems, intellectual disabilities, and memory problems.

Living with PKU

The goal of PKU treatment is to keep blood levels of phenylalanine low. Immediately after her diagnosis, Mindy began a special formula diet to control her protein intake.

As she got older, she could eat only a handful of very specific foods. She was allowed six to 10 grams of protein a day — little more than what’s found in a single chicken egg. She also had regular blood tests to track protein levels in her blood.

Mindy was raised by her grandparents, who were determined to learn as much as possible to help manage her PKU. They attended nutrition classes and talked with doctors, dietitians, and counselors. Everything she ate was closely monitored.

“They saved my life,” she says.

When her protein intake was not carefully followed, Mindy would experience headaches and mood changes. This often led to difficulties at school.

“Most people just don’t know about or understand the connection between behavior and PKU,” she says.

Mindy admits to straying from her diet as a teenager. “I would sneak foods or go buy snacks and eat them all before going back home,” she says. “I just wanted to feel normal.”

The Road to UPMC Children’s

While attending college in 2013, Mindy received a flyer from UPMC Children’s Hospital of Pittsburgh about a clinical dosing trial for Pegvaliase (Palynziq®), an injection-based experimental medicine. It would become the nation’s largest clinical trial ever conducted for adults with PKU, with more than 350 participants.

Coordinating the Pegvaliase trial at UPMC Children’s was the Center for Rare Disease Therapy, which treats children diagnosed with inherited disease disorders. If she were accepted into the trial, Mindy hoped the medicine would ease some of her PKU symptoms and allow her to eat more protein.

Following initial exams and testing at Children’s, Mindy received the good news that she could begin the treatment. Although she still needed to closely watch her diet, she was able to eat up to 30 grams of protein each day.

After three years, Mindy’s body began to resist the Pegvaliase treatment. Protein levels in her blood rose to unsafe levels. But the research team at Children’s Center for Rare Disease Therapy wasn’t ready to give up. The Center’s doctors recommended an experimental surgical treatment to cure her PKU: a liver transplant.

With Mindy’s strong immune system and overall good health, she was an ideal candidate for the procedure. On June 4, 2019, she was put on the transplant waiting list. Nine months later, Mindy got a 4 a.m. call telling her that a liver was ready. She would make medical history as the first full-liver transplant performed for the sole purpose of treating PKU.

“All my life, having PKU made me feel not normal,” say Mindy. “As soon as I woke up I asked my husband, ‘am I normal?’ When he said yes, that I could eat whatever I wanted, I started to cry.”

After several days in the hospital, Mindy was transferred to the transplant recovery unit.

“The recovery unit is where I made the most memories,” she says. “I was in a lot of pain, but I made some good friends. It was the best part of my transplant experience.

“I was going through a lot trying to accept the fact that I no longer had PKU. The nurses would come in and check on me, and not just to get my vitals. They would sit with me and talk with me about life.

“They helped me realize that I could eat what I want. That I didn’t have to order off of special menus anymore,” says Mindy.

She also remains “incredibly grateful” to the dedicated efforts of the doctors and researchers at Children’s Center for Rare Disease Therapy, led by Jerry Vockley, MD, PhD. She also expresses profound appreciation to George Mazariegos, MD, director, and the pediatric liver transplant team: Geoffrey Bond, MD; Armando Ganoza, MD; Ajai Khanna, MD; Rakesh Sindhi, MD; Kyle Soltys, MD; and James Squires, MD.

Living Without PKU

Today, Mindy’s protein levels are normal, she’s down to just one medication — and there have been no signs of rejection.

“I look at my life before and after the transplant, and life is different now,” says Mindy. “I’m not the only one to notice. People tell me I look healthier, that I smile more.”

And she and her live donor/recipient — who didn’t know Mindy before the transplant — became friends and remain in touch with each other.

Mindy offers this advice to those seeking treatments for PKU: “Know that you're not alone. It's going to be a process, so expect the unexpected, but don't be fearful of it,” she says. “I knew my life would be much better after my transplant — and it is.”