Here is some basic information on Phenylketonuria from Genetics Home Reference Of The U.S. National Library of Medicine:
Phenylketonuria (commonly known as PKU) is an inherited disorder that increases the levels of a substance called phenylalanine in the blood. Phenylalanine is a building block of proteins (an amino acid) that is obtained through the diet. It is found in all proteins and in some artificial sweeteners. If PKU is not treated, phenylalanine can build up to harmful levels in the body, causing intellectual disability and other serious health problems.
The signs and symptoms of PKU vary from mild to severe. The most severe form of this disorder is known as classic PKU. Infants with classic PKU appear normal until they are a few months old. Without treatment, these children develop permanent intellectual disability. Seizures, delayed development, behavioral problems, and psychiatric disorders are also common. Untreated individuals may have a musty or mouse-like odor as a side effect of excess phenylalanine in the body. Children with classic PKU tend to have lighter skin and hair than unaffected family members and are also likely to have skin disorders such as eczema.
The occurrence of PKU varies among ethnic groups and geographic regions worldwide. In the United States, PKU occurs in 1 in 10,000 to 15,000 newborns. Most cases of PKU are detected shortly after birth by newborn screening, and treatment is started promptly. As a result, the severe signs and symptoms of classic PKU are rarely seen.
Mutations in the PAH gene cause phenylketonuria. The PAH gene provides instructions for making an enzyme called phenylalanine hydroxylase. This enzyme converts the amino acid phenylalanine to other important compounds in the body. If gene mutations reduce the activity of phenylalanine hydroxylase, phenylalanine from the diet is not processed effectively. As a result, this amino acid can build up to toxic levels in the blood and other tissues. Because nerve cells in the brain are particularly sensitive to phenylalanine levels, excessive amounts of this substance can cause brain damage.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
So with the above as background, here is exciting news of a new treatment for phenylketonuria:
FDA NEWS RELEASE May 24, 2018
FDA approves a new treatment for PKU, a rare and serious genetic disease.
Novel enzyme therapy for adults with PKU who have uncontrolled blood phenylalanine concentrations with current treatment.
The new medication is PALYNZIQ® (pegvaliase-pqpz) Injection [Link is to the company website]:
INDICATION
PALYNZIQ® (pegvaliase-pqpz) Injection is a phenylalanine-metabolizing enzyme indicated to reduce blood phenylalanine concentrations in adult patients with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 µmol/L on existing management.
Here are excerpts from Few people know of her daughter’s genetic disorder. A mom is skiing 125 miles across Norway to change that from The Washington Post, by Dana Hedgpath, Feb 12, 2020:
Few people know of her daughter’s genetic disorder. A mom is skiing 125 miles across Norway to change that.
For 125 miles over snow and ice, a District mother [Alison Reynolds] will cross-country ski across Norway later this month to raise money and awareness for her daughter’s rare genetic disorder.
Tia, her daughter of has phenylketonuria, often referred to as PKU. A person with the condition has a damaged enzyme that breaks down an amino acid called phenylalanine, or Phe, which is found in protein and many foods.
Without that enzyme to process Phe, PKU patients can have a dangerous buildup in the bloodstream if they eat foods with high levels of protein, such as milk, nuts, pasta and cheese. Typically, a PKU patient can consume six to seven grams of protein a day, compared with other adults, who can consume at least 50 to 60 grams daily.
For a person with PKU, a high level of Phe can lead to brain damage.
“It basically means that food is toxic to a PKU patient’s brain,” said [Alison] Reynolds, 46.
After about a year of training and promoting her Norwegian journey in a blog, Reynolds said she has raised about $890,000 — more than double her original goal — from friends, family and businesses.
Reynolds expects to have plenty of quiet time — in short supply in a house with four children — while skiing with a guide in a single-file formation. It will allow her to reflect on her family’s journey with PKU, she said.“I expect it will be a combination of trying to live in the moment and watching the conditions and terrain to be safe,” she said. “It will also likely be a sensory overload.”
PKU patients have to stick to a strict, very low-protein diet and consume medically modified — and expensive — formula and foods. An eight-ounce box of pasta for someone with PKU costs about $15, and a loaf of bread can cost more than $10. Families can spend tens of thousands of dollars a year on foods that are rarely covered by insurance.
There are no outward signs of PKU at birth. In the United States — where about 16,500 people have the condition — it is diagnosed shortly after birth through screening that began in the 1960s. Newborns are tested with a blood sample from the heel of the foot.
A person with high levels of Phe in their blood can suffer irreversible neurological issues.
The disorder is typically passed to a child when two parents are carriers but often don’t know they have it.
‘A few days after Tia was born, Reynolds got a call from a lab in California indicating that her daughter tested positive for PKU.
For Tia, there were frequent struggles. When her Phe levels were too high, she felt like she was in a fog. Low energy would keep her from regularly playing tennis and lacrosse.
She sometimes would drink formula developed for those who suffer from PKU in a bathroom stall to avoid being teased.
There were few drugs on the market to help those with the disorder 10 years ago. Developing drugs is costly, and because PKU afflicts relatively few people, the market for sales is small.
Tia’s family thought more should be done.
Reynolds said that in the past 17 years, she and her family, along with the national PKU group they established, have raised nearly $7 million.
Raymond Stevens, who has studied PKU for nearly 30 years and got approval from the Food and Drug Administration for a drug treatment that Michaux helped fund, called Reynolds and her parents “heroes for stepping up” in fighting the disorder.
“They had the time. They had the passion. They had the resources and they had the network,” Stevens said. “They wanted to make a difference, and they did.”
‘It almost feels like I’m cured’ [daughter Tia said].
The drug that Stevens helped develop, called Palynziq, came onto the market in 2018 with the help of BioMarin Pharmaceutical in San Rafael, Calif.
Last fall, Tia started using the drug, which she injects daily into her stomach with a one-inch needle. The drug helps to lower Phe levels in the blood, but it can have side effects — and it’s expensive, although treatments are often covered by insurance.
For Tia, the drug has been “a major game-changer,” her mother said.
In December, doctors at Children’s National Hospital called with exciting news: Her Phe levels were at zero — something unheard of for Tia.
Tia’s grandmother, who lives across the street in the Spring Valley neighborhood of Washington and learned to cook Tia’s specialty foods, began to cry when she heard the news.
Tia has more energy to play sports, can better focus on her studies and, most importantly, has dramatically changed her diet. She’s able to eat macaroni and cheese, yogurt, pizza, shrimp and pancakes, all in moderation.
“It’s exciting for me that I don’t have to eat special food and formula anymore, but it makes me feel bad for other kids,” she said, referring to those who don’t have — or can’t afford — the drugs. “It is a humbling reminder. It almost feels like I’m cured.”
