The Dutch heel prick program was expanded on October 1 to include a 27th disease. From then on, newborn boys are screened for the disease adrenoleukodystrophy, a metabolic disease. It is the first national screening for the condition worldwide, with a central role for Amsterdam UMC.
Laura den Edel30 September 2023, 03:00
Almost all Dutch parents have to deal with it, the heel prick. The prick in the heel checks the blood of more than 99 percent of newborns for 26 congenital diseases. Only a few, about three per thousand parent couples, hear back from their GP. Now that ALD has been added to the injection as the 27th disease for boys, the National Institute for Public Health and the Environment (RIVM) expects to find five to ten boys with the disease every year.
In 2013, pediatric neurologist Marc Engelen and medical biochemist Stephan Kemp from Amsterdam UMC proposed to the Health Council to include ALD in the advice to the Minister of Health, Welfare and Sport on expanding heel prick screening. The two lead the team that researches the disease and Engelen treats children and adults with the disease.
Treatable condition
ALD met the requirements: the disease is partly treatable and screening is possible. Because the deadly variant of the disease only occurs in boys and is treatable, the Health Council has recommended that only boys be screened for the disease.
Kemp, lead researcher in the Genetic Metabolic Diseases Laboratory, was asked to set up a trial in 2018: “Technically, it is quite simple to test blood for ALD. We had to ensure that only boys with this disease could be detected, without detecting girls or untreatable diseases. Other countries screen both boys and girls.”
The main argument against screening all babies is that there is no treatment for the consequences of ALD in women. The disease causes damage to the nerves in the spinal cord.
Freakish disease
In 1993 it was discovered that mutations in the so-called ABCD1 gene cause the metabolic disease ALD. Due to these mutations, certain body’s own fatty acids are not broken down properly. Instead, they lengthen, with damaging effects on the brain, spinal cord and adrenal glands. It is a capricious disease: doctors and researchers cannot yet predict how ALD will manifest itself per patient.
According to pediatric neurologist Engelen, there are three common presentations of ALD. First, a boy suddenly develops behavioral problems or his academic performance suddenly deteriorates. Subsequently, neurological complaints arise, such as motor limitations or epileptic seizures. Both are a result of progressive damage to the white matter of the brain, leukodystrophy.
“At this stage, treatment is no longer useful,” says Engelen. “The boy will continue to deteriorate and eventually die. By periodically making MRI scans of boys with ALD, we can detect leukodystrophy at an early stage and make treatment worthwhile. We do not do that treatment, a bone marrow transplant, before leukodystrophy develops, because it is risky and not all boys develop this damage.”
Hormoontekort
The second manifestation revolves around complaints caused by adrenal insufficiency. These complaints, including fatigue, have often existed for a long time and are non-specific. Engelen: “With a serious deficiency of adrenal cortex hormone, the ‘stress hormone’ cortisone, someone can suddenly become very ill due to fever or an accident or physical stress. It can lead to hospital admission. By monitoring boys with ALD, we can start hormone supplementation in time and prevent disease.”
The third manifestation occurs in adulthood in both men and women and causes progressive damage to the spinal cord. “That leads to walking problems and incontinence. It eventually affects everyone with ALD, but the severity is quite variable. There is no treatment yet that can prevent or stop this.”
In the near future, the largest group of patients will be traced using the heel prick or family research, says Engelen. “They will not have any symptoms yet. We monitor these boys closely with a six-monthly check-up so that if we see any complications, we can treat them quickly.”
Parents who are told from October 1 that their newborn son has tested positive for ALD will receive an appointment at Amsterdam UMC the next day (see box). Boys with the diagnosis, made by the pediatric neurologist, then come to the hospital every six months for a number of examinations.
Four tests
The research team of medical biochemist Stephan Kemp had to find new ways to detect only boys with adrenoleukodystrophy (ALD) using the heel prick. Together with the National Institute for Public Health and the Environment (RIVM) and the departments of Human Genetics and Genetic Metabolic Diseases of the Amsterdam UMC, the team has developed an algorithm with which the blood of newborns is examined in four consecutive ways.
First, the blood drop is tested for a so-called biomarker known as C26:0LPC. This marker shows the longer fatty acids. The number of X chromosomes is counted with the so-called X counter, because women have two and men have one.
Positive results with one X chromosome continue. C26:0LPC is then measured again with a more sensitive and specific test. If the value is elevated, a DNA test for mutations on the ABCD1 gene will follow. Only if the result is positive in that step will the parents be invited for a consultation.
‘We mainly feel relief’
ALD was found in Annelies’ son in 2021 thanks to a trial with the heel prick. Annelies: “Five weeks after Joep’s birth, in December 2021, we received a call from the GP. He asked if my friend and I were sitting and said that something had come out of the heel prick. He called the disease adrenoleukodystrophy and couldn’t tell us much else. For that we had to go to Amsterdam UMC the next day.”
“The 24 hours until that appointment were hellish, we didn’t know what to think. In the hospital, Dr. Engelen immediately said: ‘You must be terrified, but you have a healthy boy who can live to be a hundred.’ We could kiss him!”
“After this we heard what the disease entails, but also that Joep will not die from it. Because it is hereditary, our eldest son has also been examined, as has my sister, because she could pass it on. None of them have it, thankfully.”
“Joep’s blood is now checked every six months, an MRI will soon be added. Furthermore, he is an ordinary curious boy, the diagnosis plays no role in our lives. No one can predict how it will develop, so there’s no point in worrying. For us, relief and gratitude predominate.”
The names have been changed at the request of the parents.
2023-09-30 14:20:40
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