Without screening, prenatal diagnosis and starting treatment in time are almost impossible / ALD is usually fatal: a genetic defect leads to the destruction of myelin / Leipzig University Hospital is a leading center for the treatment of children and adults with ALD

ALD (adrenoleukodystrophy) is a disease that’s as rare as it is insidious. At least one in 17,000 newborns is affected, mostly boys. If undetected and hence untreated, it usually leads to disability and death. Leipzig University Hospital is one of the few centers in Germany where the disease can be treated with the benefit of interdisciplinary collaboration, including by using stem cell transplantation (SCT) and other modern therapeutic techniques. “Unfortunately, however, ALD is often detected too late,” says Dr. Jörn-Sven Kühl, an acclaimed pediatric SCT expert. “It needs to be included in newborn screening. This would greatly improve the chances of timely diagnosis and therapy in many of those affected.”

ALD is a hereditary metabolic condition and belongs to the group of rare diseases. Due to a genetic defect, certain fatty acids can’t be broken down. They damage the brain and spinal cord as well as the adrenal glands. In boys, this genetic defect often leads to the destruction of the “white matter” of the brain, the myelin, via acute inflammation. If left untreated, the disease is often fatal, since important nerve functions may fail as the disease progresses. In Germany, there are only a few specialized centers for ALD transplantation. “We transplant two or three children every year in this way (and as many as four last year), and thus do about two thirds of all transplants throughout Germany,” says Dr. Kühl, head of pediatric stem cell transplantation at the Department of Pediatric Oncology, Hematology and Hemostaseology at Leipzig University Hospital. In the meantime, the department has acquired experience with 50 transplanted children. The clinical care of the young patients in Leipzig is carried out in cooperation with the hospital’s Neuropediatrics department headed by Professor Andreas Merkenschlager. For many years, Leipzig University Hospital has worked closely with neurologists at University Children’s Hospital in Göttingen.

Transplantation can stop inflammation

The severe form of progression practically only affects boys because it’s what’s known as an X-linked disease. “One third of all boys up to the age of ten develop characteristics of what we call the ‘infantile cerebral progressive form of adrenoleukodystrophy,’” explains Kühl. “They’re usually completely unremarkable children with normal development until the onset of the disease,” he adds. Sometimes, he says, it’s noticeable when those affected are diagnosed with adrenal cortical weakness (Addison’s disease). But this disease is also difficult to diagnose and it’s therefore often detected late – too late.

“If certain behavioral abnormalities are detected in affected children, it’s usually already too late for a transplant, because the brain has already suffered major damage,” explains Dr. Kühl. “That’s because transplanting stem cells doesn’t fix anything. What’s broken in the brain stays broken. But it can stop the inflammation from leading to the breakdown of brain matter.” However, because this process may take months, transplantation is no longer useful in advanced patients.

No shortage of donations

“We need newborn screening,” emphasizes Dr. Kühl. He realizes that many are critical of this view because not all affected children fall ill. But there are extremely safe transplant methods nowadays, he points out. If transplantation is done early enough following the onset of the disease, it’s been proven to be an effective therapy with a very good outcome for patients, he says. “But we can currently only offer it to far too few children, because without screening and regular MRI checks, timely diagnosis is almost impossible,” he explains.

The consequences can be dramatic: “Within five years, disabilities of the most severe kind develop. The patient is bedridden, and in very many cases, the disease leads to early death.” Without the screening of newborns for ALD, the possibility of treatment comes too late for around half of these patients.

Yet, in contrast to organ donation, there’s no shortage of donated stem cells in Germany. “Although donations are sought worldwide, we can usually use those from Germany,” says Dr. Kühl.

Care for all age groups at Leipzig University Hospital

At Leipzig University Hospital, not only children but also adults suffering from the consequences of the disease are treated. Senior physician Dr. Wolfgang Köhler from the Clinic and Polyclinic for Neurology looks after adult patients with ALD and other leukodystrophies. Working with Professor Uwe Platzbecker, Director of Hematology, and his team, a transplant center for men with cerebral ALD has been established at Leipzig University Hospital – something which is almost unique in Germany. “The first transplantations in adults were started in 2018 at Leipzig University Hospital with the active support of Professor Dietger Niederwieser, who headed Hematology there until 2018,” emphasizes Dr. Kühl. “We’re now working together on new gene therapy approaches and new drugs to improve the situation for patients.”

https://www.uniklinikum-leipzig.de