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Rare Disease Day brings attention to a puzzle lacking pieces
Rare Disease Day 2024 graphic

Parents of children with rare diseases can feel like they have been handed a puzzle, but one lacking all the pieces. In recognition of Rare Disease Day (Feb. 29), we share the experience of one Georgia family and their efforts at puzzle-solving.

In 2019, two weeks after the birth of their daughter, Scarlett, the Alonzo family received a call from the state of Georgia’s newborn screening program. The results of a blood test showed Scarlett had a rare deficiency in an enzyme that breaks down the amino acid arginine. Scarlett didn’t have any symptoms at that point, but without changes in her diet, she could be expected to develop mobility problems, followed by a loss of developmental milestones and the ability to walk, and possibly seizures.

“We were very surprised — we almost didn’t believe it,” Scarlett’s father Alonzo de Alonzo Peres says. “Those were some very hard days.”

Soon after Scarlett’s birth, the Alonzos met with Emory medical geneticist Rossana Sanchez Russo, who specializes in metabolic disorders. She has evaluated most of the handful of children in Georgia with arginase deficiency, as well as some from neighboring states. She says children with arginase deficiency tend to show symptoms around age three, and some of her patients have symptoms of spasticity, impairing use of their legs.

The Alonzos also met with nutritionists at Emory’s Medical Nutrition Therapy for Prevention (MNT4P) program. The MNT4P nutritionists provided them with medical information in Spanish since that is their household language (the Alonzos came to Georgia from Guatemala more than 20 years ago).

The family was instructed to provide Scarlett a special low-protein diet, along with nutritional supplements.

“The goal of newborn screening is to identify conditions like this,” Sanchez Russo says. “Prompt intervention can really make a difference in preventing unfavorable outcomes.”

When the Alonzos returned from Atlanta to their home in Ellijay, they hugged their other children and explained the news to them.

Arginase deficiency is one of the rarer metabolic diseases covered by newborn screening programs. In some ways, it resembles phenylketonuria, which Georgia has been screening for since 1968. People with phenylketonuria lack an enzyme that breaks down another amino acid, phenylalanine. The general approach is the same: Parents are advised to modify their child’s diet, with the aim of preventing future complications.

Scarlett with her mother, Magdalena Alonzo.

But unlike phenylketonuria and several other metabolic disorders, with arginase deficiency, symptoms may progress despite a restricted diet — and there is no approved enzyme replacement therapy available. That’s why Sanchez Russo asked the Alonzos to participate in a clinical trial testing a potential treatment.

To be part of the study, the Alonzos got up at 5 a.m. and drove Scarlett from Ellijay to Atlanta once a week, so that she could receive an infusion providing a stabilized form of the arginase enzyme.

“We did it so that Scarlett might have a better future,” says her mother Magdalena Alonzo. “But also to help other children with this condition.”

The Alonzos have met another family in Tennessee whose child has arginase deficiency, and have met others through an online dietary education program.

“Because of the many barriers, ensuring that people from diverse backgrounds join clinical trials is important for health equity,” Sanchez Russo says.

At age two, Scarlett was the youngest participant in the study, which took place in the United States and several European countries. The double-blind period, during which the family didn’t know whether Scarlett was receiving active enzyme or a placebo, lasted for 24 weeks. The study was eventually “unblinded” and the family learned she had been receiving active enzyme.

So far, Scarlett has avoided the neurological symptoms typical for children with arginase deficiency, but her father says sometimes she shows periods of fatigue and low appetite. She has managed to avoid excess ammonia in her blood, a complication of arginase deficiency that can require hospitalization.

Scarlett now attends pre-K in Ellijay. Her parents talked with the school’s director and explained her special dietary needs, and the school’s staff was supportive. Scarlett will tell teachers or classmates that a food has “too much protein” if she is offered something she’s not supposed to eat, her parents say.

The study testing the experimental therapy was published in January, with Sanchez Russo as the lead author. It showed that the stabilized enzyme could effectively control excess arginine levels in participants’ blood. Based on this, the treatment was approved in Europe. However, information on whether the treatment regimen prevented mobility problems was limited, and the U.S. FDA has asked the manufacturer for more data on patients’ mobility outcomes.

What this means: Despite having their daughter receive an experimental treatment for almost two years, the Alonzos don’t know if they will be able to obtain it in the future. The company that makes the arginase enzyme, located in Sweden, announced in December that it is re-applying to the FDA.

Emory medical geneticist Rossana Sanchez Russo assesses neurological function for Scarlett Alonzo, a clinical trial participant.

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