dr Jörn-Sven Kühl, stem cell transplant expert at UKL: "ALD should be included in newborn screening"

ALD - adrenoleukodystrophy - is a disease that is as rare as it is insidious. At least 17000 in XNUMX newborns is affected, mostly boys. Undetected and untreated, it usually leads to disability and death. The University Hospital Leipzig (UKL) is one of the few centers in Germany where the disease can be treated in interdisciplinary cooperation, including stem cell transplantation (SCT) and other modern therapeutic approaches.

"Unfortunately, however, ALD is often recognized too late," notes Dr. Jörn-Sven Kühl, a pediatric SCT expert recognized throughout Europe, states: “It must therefore be included in newborn screening. This would greatly improve the chances of timely diagnosis and therapy for many of those affected.”

ALD is an inherited metabolic disease and belongs to the group of rare diseases. Due to a genetic error, certain fatty acids cannot 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 brain substance", the myelin, via acute inflammation. If left untreated, the disease is often fatal, as important nerve functions can fail as the disease progresses. In Germany there are only a few specialized centers for ALD transplantation. "We transplant two to three children per year, four in the past year, and thus an estimated two thirds of all transplants in Germany," says PD Dr. Kühl, Head of Pediatric Stem Cell Transplantation at UKL's Department of Pediatric Oncology, Hematology and Hemostaseology. There is now experience with 50 transplanted children. The clinical care of the children in Leipzig is carried out in cooperation with the UKL neuropaediatrics headed by Prof. Andreas Merkenschlager. Nationally, there has been close cooperation with the neurologists of the Göttingen University Children's Clinic for many years.

Transplantation can stop the course of inflammation

The severe form practically only affects boys because it is a so-called X-linked disease. "A third of all boys by the age of 10 develop what we call 'childhood cerebral adrenoleukodystrophy'," describes the UKL expert. "Up until the onset of the disease, these are usually completely normal children with normal development," says Kühl. Sometimes it is noticeable when those affected are diagnosed with adrenal insufficiency (Addison's disease). However, this disease is also difficult to diagnose and is therefore often recognized too late.

"If certain behavioral problems are found in the affected children, it is usually too late for a transplant because the brain has already been badly damaged," explains Dr. Cool. “Because stem cell transplantation doesn't fix anything. What's broken in the brain stays broken. But it can stop the inflammation that leads to the breakdown of brain matter." Since this process can take months, however, transplantation no longer makes sense in advanced patients.

No shortage of donations

"We need newborn screening," emphasizes senior physician Kühl and knows that this is viewed critically by many, precisely because not all affected children fall ill. There are such safe transplant procedures nowadays, he emphasizes. If transplanted early enough at the onset of the disease, it has been proven to be an effective therapy with very good chances for the patient. "But we can offer it to far too few because without screening and regular MRI checks, timely diagnosis is almost impossible," explains the specialist in paediatrics.

The consequences can be dramatic: "Within five years, the most severe disabilities develop, confinement to bed, and in many cases the disease leads to early death." Without screening of newborns, a possible treatment comes too late for around half of these patients.

In contrast to organ donation, there is no shortage of donated stem cells in Germany. "Although donations are sought worldwide, we can usually fall back on those from Germany," says Dr. Cool

Care for all age groups at the UKL

Not only children but also adults suffering from the consequences of the disease are treated at the Leipzig University Hospital. Senior Physician Dr. Wolfgang Köhler from the Clinic and Polyclinic for Neurology looks after the adult patients with ALD and other leukodystrophies. In close cooperation with Prof. Uwe Platzbecker, Director of UKL Hematology, and his team, a transplant center for men with cerebral ALD that is almost unique in Germany has been established at the UKL. "The first transplantations in adults were already started in 2018 at the UKL - with the active support of Prof. Dietger Niederwieser, who was in charge of hematology at the UKL until 2018," emphasizes Dr. Cool, "we are now working together on new gene therapy approaches and new drugs to improve the situation for patients."

Source: Press release University Hospital Leipzig from 02.08.2022