Navigation Links
Therapy should extend beyond childhood

By systematically analysing MRI changes occuring in the brains of children with the metabolic disease glutaric aciduria type I researchers at Heidelberg University Hospital have succeeded for the first time in demonstrating reversible and permanent brain damage as well as elucidating its temporal evolution.

The Heidelberg researchers now assume that during the course of the disease, the products of metabolism cause not only acute, but chronic toxic damage as well. Therapy should thus be extended to prevent long-term brain damage.

These new insights enhance the understanding of the natural course of the disease and confirm the benefit and consequently the necessity of newborn screening for rare metabolic diseases and neonatal therapy. The study was published in the prestigious journal Brain.

Permanent damage when treatment is delayed

One of 100,000 newborns suffers from the rare metabolic disorder glutaric aciduria type I. Affected children are unable to break down certain amino acids (lysine, hydroxylysine, and tryptophan), which are components of proteins, but produce pathological metabolites that accumulate and can damage the developing brain.

Even before birth, brain changes indicating delayed development occur, which however are reversible if they receive adequate treatment in time. Permanent brain damage usually occurs in clinically inconspicuous babies if the diagnosis is not made in time and treatment is delayed.

Babies are initially free of symptoms / Severe crises during infancy and childhood

As newborns and young babies, the patients are initially inconspicuous. If not treated, they undergo a severe crisis at the age of 3 to 36 months. As the same deep regions of the brain are affected as in Huntington's disease, the children have similar movement disorders but their intelligence is usually spared by the neurodegenerative process.

However, the children's prognosis is favourable if the disease is detected early by newborn screening, which -using a drop of blood taken from the heel- is carried out in Germany for all newborns. The diagnosis after birth is the most important condition for successful treatment, i.e. normal development and prevention of irreversible cerebral injury. The therapy consists of a special diet low in the amino acid lysine, and supplemented with carnitine, an endogenous carrier for fatty acids, which is lost through urine in this disease. In addition, intensive emergency treatment of the metabolism must be carried out to prevent a metabolic crisis during febrile infections.

For their study, an international interdisciplinary research group of neuroradiologists and pediatricians headed by Dr. Stefan Klker from the Center for Pediatric and Youth Medicine and Dr. Inga Harting from the Department of Neuroradiology examined 38 patients from newborns to adulthood, comparing MRI changes with neurological symptoms and analyzing the time patterns.

Reversible and irreversible changes occur

They discovered that MRI changes in certain regions of the brain (e.g. in the white matter and cerebral cortex) occured frequently and in all patients, whereas changes in the basal ganglia occurred only in patients who had experienced encephalopathic crises. The changes outside of the basal ganglia were quite variable, some were reversible, and some were apparent as early as the neonatal stage and had no clinical significance. In contrast, the changes in the basal ganglia were irreversible and were clearly associated with the development of severe movement disorders.

The Heidelberg researchers now assume that during the course of the disease, the products of metabolism cause not only acute, but chronic toxic damage as well. Therapy should thus be extended to prevent long-term brain damage.

The Heidelberg researchers hypothesize that in the course of the disease, abnormally accumulating metabolites not only give rise to acute, but also to chronic toxic damage. For treatment purposes, this would mean that the duration of current therapy should be extended beyond childhood to prevent long-term changes and damage to the brain. This remains to be elucidated by follow-up studies.

Heidelberg Metabolism Center screens 100,000 newborns annually

Newborn screening in Germany is carried out to detect glutaric aciduria type I and 13 other diseases. The Metabolism Center of the Heidelberg Clinic for Pediatric and Youth Medicine carries out newborn screening for 100,000 newborns annually. The current guidelines in Germany and three other European countries for the diagnosis and therapy of children with this rare metabolic disease were compiled by an international guideline group headed by Dr. Klker. Parallel to this, the same working group carried out translational studies to examine new therapy approaches in a mouse model.


Contact: Dr. med. Inga Harting
University Hospital Heidelberg

Related medicine news :

1. Carboxytherapy and Mesotherapy Unproven, Warns The Physicians Coalition for Injectable Safety
2. Ongoing Study Shows That Endovascular Therapy is Associated With High Cure Rate for Childhood Eye Cancer
3. Northwest Hospital Introduces Hyperbaric Oxygen Therapy
4. Most Not Worried by Delayed Prostate Cancer Therapy
5. Oral Chemotherapy Offers Patients a More Convenient, Less Invasive Treatment Option
6. Xoft Expands Cancer Treatment Platform With Launch of Skin Cancer Electronic Brachytherapy Trial at AAPM Meeting
7. Cold Laser Technology Made Even More Accessible with Powerful New Product Available from Laser-Therapy.US
8. First Customer Installs CyberKnife System in Existing Radiation Therapy Vault
9. Abilify Has Made Strong Gains in Patient Share Across All Lines of Therapy Since Last Years Analysis of Prescribing Trends in Schizophrenia
10. Life after chemotherapy: Daily tasks, quality of life may be affected, MU researcher finds
11. Nexavar in Combination with Chemotherapy Shown to Extend Progression-Free Survival in Patients with Advanced Breast Cancer
Post Your Comments:
Related Image:
Therapy should extend beyond childhood
(Date:12/1/2015)... ... December 01, 2015 , ... December 1, 2015 ... of the company’s growing product line of food safety and seafood fraud prevention ... (Oncorhynchus nerka) – allow InstantLabs to offer fast, reliable species identification for the ...
(Date:12/1/2015)... ... December 01, 2015 , ... The workstation ... lifted as IMAGE Information Systems launches MED-TAB™ -- the world’s first portable DICOM-calibrated ... from November 29 to December 4, 2015. , MED-TAB is expected to ...
(Date:12/1/2015)... ... December 01, 2015 , ... ... is everything. That is why Hollister Incorporated has launched the VaPro Plus Pocket™ ... next product in the VaPro touch free catheter portfolio,” said Michael Gresavage, Vice ...
(Date:12/1/2015)... ... December 01, 2015 , ... ... has been awarded a fixed price per sprint agile development contract to support ... $34 million over five years, provides software engineering, infrastructure, as well as operations ...
(Date:12/1/2015)... , ... December 01, 2015 , ... XTC Semifinals ... 10 semi-finalists to head to Las Vegas for CES 2016, the world’s largest Consumer ... of Consumer Technology Association Gary Shapiro, Founding Partner of Pacific Investments Veronica Serra, and ...
Breaking Medicine News(10 mins):
(Date:12/1/2015)... Dec. 1, 2015 WellStar Health System has ... Texas -based Tenet Healthcare,s five metro ... approved the strategic move following the conclusion of the ... clinical care models and patient safety programs that have ... to new communities. --> ...
(Date:12/1/2015)... , Dec. 1, 2015  Eyeon Therapeutics has ... dry eye treatments based on a charged hydrophilic ... delivery CDMO.  The product has been shown to ... previously published.  Mark Mitchnick , MD, CEO ... protection to additional polymers in conjunction with a ...
(Date:12/1/2015)... 1, 2015 Pharma Tech Outlook recently conducted ... Clinical Data Management Solution Providers - 2015 .  After ... comprising CEOs, CIOs, VCs, analysts, and the Pharma Tech ... of top 10 clinical data management solution providers (check ... 14 and 36 respectively). --> ...
Breaking Medicine Technology: