Dear Dr. Greene, I have a son who was born on Aug 12, 1995. He was normal from birth to about 1 year old. He could stand up and hold onto furniture and walk around. He could speak a few words like “daddy,” “one,” “two” etc. But when he was about 15 months his development was going backward gradually. At first, he did not stand up any more. Later on he did not speak, he cannot crawl, he could not sit. Now his neck does not have enough strength to support his head. And so very often his head is down. Also, his hands are getting weaker and weaker. In May 1997, he had to use a gastric tube to take any kind of fluid. However, he still can take solid food, but not completely like a normal child does. Our pediatrician and the neurologists said that he has neurodegenerative disorder. They have done tests on him but they still cannot find out the cause. They said that this is most probably something related to the gene and so there is no way to make him recover. We are really sorry to hear about this. We do not mean that we do not believe in our pediatrician and neurologists. But as a parent, I could not just see my child getting worse and worse and die some day. Therefore, I am now checking on the Internet to see if some one can help my child. Please give us some comments. Thanks,
T.M. – HO
Dr. Greene’s Answer:
What a heart-wrenching saga, T.M.! Childhood, at its core, is a time of amazing growth and development. As parents, we thrill as our little ones achieve each new developmental milestone (with perhaps a bittersweet twinge at how quickly it all goes by). But how jarring, how deeply wrong, to watch helplessly as your son’s achievements slip away.
The neurodegenerative disorders of childhood are a diverse group of rare diseases that until recently were a death sentence of the most horrible kind. These diseases can result from genetic problems, biochemical defects, viral infections, or toxic substances, but they all share the same grim story. A previously healthy child begins to deteriorate. The hallmark of these diseases is a progressive loss of speech, hearing, vision, and strength. Seizures, feeding difficulties, and loss of intellect often accompany this downhill course. And up until the last several years, they continued relentlessly until the child died.
A few years ago, Augusto and Michaela Odone’s son was diagnosed with a neurodegenerative disorder. Like you, they were told by excellent physicians that their little boy had absolutely no chance, but would deteriorate steadily. Like you, they continued to search for hope. Eventually, they discovered a therapy that came to be known as Lorenzo’s Oil, named after their little boy, Lorenzo. Their heroic quest is chronicled in a powerful movie called “Lorenzo’s Oil.” I highly recommend watching this film if you haven’t seen it.
I met the Odones at an Institute of Medicine meeting in 1996, eleven years after the rapidly progressive disease was supposed to have killed their boy. They glowed with pride as they talked of a song that Lorenzo and his mother had just written with Phil Collins. Lorenzo’s Oil isn’t a miracle cure, but it can provide real help for children with one type of neurodegenerative disease – adrenoleukodystrophy. Lorenzo’s Oil is the first of a growing number of increasingly promising therapies for many of the neurodegenerative disorders of childhood.
The outcome of these disorders has historically been so uniformly dismal that it is quite tempting to stop short of pinpointing which specific disorder a child has once a diagnosis of neurodegenerative disorder has been made.
Knowing exactly which disorder is very worthwhile. You’ve been told that your son has one of the genetic neurodegenerative disorders. These are grouped into four categories: sphingolipidoses, neuronal ceroid lipofuscinoses, adrenoleukodystrophy (like Lorenzo), and sialidosis. These may be distinguished from one another based on head CT, head MRI, nerve conduction velocities, visual evoked potentials, auditory evoked potentials, electroretinography, and to a lesser extent, EEG’s. When needed, skin, conjunctival, and nerve biopsies can help pinpoint the diagnosis. There are now also blood tests and DNA tests that can help diagnose these conditions. Finally, specific enzyme assays and cultures can distinguish between individual disorders within each group. Pediatricians, neurologists, and geneticists must often work in conjunction to make these diagnoses.
The sphingolipidoses include six specific diseases: Niemann-Pick disease, Gaucher disease, Krabbe disease (globoid cell leukodystrophy), metachromatic leukodystrophy (MLD), GM1 gangliosidosis, and GM2 gangliosidosis. What these conditions all have in common is the ability to destruct the storage of fats within nerve cells. My up-to-date pediatric textbook states that each of these diseases is invariably fatal.
But the situation is rapidly changing! The April 16, 1998 issue of the New England Journal of Medicine reported the dramatic story of 5 children with Krabbe disease (globoid leukodystrophy) who experienced reversal of neurological symptoms following bone marrow transplantation. Since then, medical journals abound with cases of patients with sphingolipidoses being treated with bone marrow transplants.
Over the last decade, hundreds of children have received bone marrow transplants in an attempt to treat these devastating conditions. While the results have been mixed, researchers have begun to narrow down which children this therapy is most likely to help. In particular, children with Krabbe disease, metachromatic leukodystrophy, and to a lesser extent Gaucher disease, have been successfully treated with bone marrow transplants (J Inherit Metab Dis 1995).
I suggest contacting the University of Minnesota Medical School in Minneapolis where many of the most exciting successes have occurred. Other pediatric centers worldwide also have programs working to treat these disorders with bone marrow transplantations, many with positive results.
From universities on three continents, in Tokyo, Japan (Acta Paediatr Jpn, Apr 1996), Munchen, Germany (Cytokines Mol Ther, Jun 1996), and Pittsburgh, USA (Gene Therapy, Apr 1996) have come reports that gene therapy – replacing the gene that is responsible for making the missing enzymes – is becoming a practical possibility for metachromatic leukodystrophy (MLD). This type of treatment, when refined, will be the ideal treatment for this type of disease.
Neuronal Ceroid Lipofuscinoses
The neuronal ceroid lipofuscinoses consist of four inherited disorders: infantile type (Haltia-Santavuori), late infantile (Jansky-Bielschowsky), juvenile type (Spielmeyer-Vogt), and adult type (Kufs or Parry disease). Recetly, scientists have looked at reclassifying these disorders on the basis of newer molecular findings, They are characterized by the storage of a fluorescent substance within the nerve cells and are associated with variable but progressive symptoms. This group of illnesses is also sometimes called Batten disease.
Bone marrow transplant has been successful in treating this group of illnesses (Cell Transplant, Jul 1995). In addition, carnitine, a dietary supplement, has been shown to slow the progress of these diseases (J Neurosci Res, Oct 1997).Researchers are currently assessing the potential benefits of chaperone therapy, enzyme replacement therapy, gene therapy, and stem cell therapy.
Sialidosis is divided into sialidosis type I and sialidosis type II. These conditions are caused by a missing enzyme (called sialidase or alpha-neuraminidase) that results in the accumulation of sialic acid in the nerve cells. Type I is usually first noted in teenagers who develop visual changes and abnormal movements. Type II can show up in infants and toddlers.
One of the most interesting developments in the treatment of sialidosis happened by accident. In Japan, two children who were missing the key enzyme (sialidase) began producing it when they got Epstein Barr virus! Further research is now underway regarding the therapeutic possibilities of this fortuitous occurrence (J Neurol Sci, Jul 1995).
Currently, researchers are also trying to understand the possible roles that bone marrow transplantation and gene therapy may play in treating these conditions.
Adrenoleukodystrophy is one of the genetic neurodegenerative disorders. The hallmark of this group of disorders is a slow but progressive deterioration of brain function. These disorders are grouped into four categories: sphingolipidoses, neuronal ceroid lipofuscinoses, adrenoleukodystrophy (like Lorenzo, whose story is portrayed in the movie “Lorenzo’s Oil”), and sialidosis. These may be distinguished from one another based on head CT, head MRI, nerve conduction velocities, visual evoked potentials, auditory evoked potentials, electroretinography, and to a lesser extent, EEG’s. There are now also blood tests and DNA tests that can help diagnose these conditions.
In Adrenoleukodystrophy, the myelin, also known as the white matter, is lost from the nerve cells. The myelin is supposed to be the insulation around the nerve that allows it to transmit electrical impulses properly. Adrenoleukodystrophy can be broken down into three broad groups of disorders (classic, neonatal, and adrenomyeloneuropathy), though doctors and scientists now think there are as many as eight different sub-types of adrenoleukodystrophies. All of these subtypes result in slow decline in brain function. Some may be associated with problems with the adrenal glands, organs that regulate various hormones in the body.
Classic Adrenoleukodystrophy tends to become symptomatic between 5 to 15 years of age. Neonatal Adrenoleukodystrophy, as the name suggests, is generally noted at or near the time of birth. Patients with Adrenomyeloneuropathy may first show neurologic changes as late as 30 to 50 years old, though they often have problems with their adrenal glands as children. Then there are some people with adrenoleukodystrophy who have nearly no symptoms!
There are currently several treatments available that seem to improve the quality of life for these children, though currently there is no cure. Lorenzo’s Oil, a dietary supplement made from olive oil and rapeseed oil, is the most famous treatment, but by no means the only option. Adrenoleukodystrophy is one of the neurodegenerative diseases of childhood for which bone marrow transplantation is most successful. The transplant may help prevent neurological deterioration in patients, when performed early enough. Some children also need “adrenal replacement therapy,” meaning medication to make up for the fact that the adrenal gland is not working properly.
Then there are many types of medications being studied as future treatments for these devastating conditions. Some scientists are finding evidence that Lovastatin, a medication commonly used to lower cholesterol, might help people with adrenoleukodystrophy.
One of the most exciting developments is the possibility of actually transplanting myelin-producing cells. While embryonic stem cell research has been highly controversial, it may offer hope for improved function in patients devastated by neurologic deterioration. Augusto Odone, Lorenzo’s father, reports that “indeed this work is now so advanced that an increasing number of neurologists and clinicians on both sides of the Atlantic believe it will soon be possible to conduct transplantation trials on myelin disease sufferers.”
If your child if affected by this condition, please also consider speaking with your doctors about checking other family members for these conditions. These diseases are often hereditary (meaning they are passed on from parents to children) and some people with these diseases may be asymptomatic (meaning they are not acting sick), Since some of the current treatments are most effective early-on in the course of the disease, early diagnosis and early treatment can be crucial!
Anyone whose child has a myelin disease (and perhaps anyone with any neurodegenerative disease) should contact Augusto Odone, Lorenzo’s father. His Myelin Project is an inspiring example of what can happen when parents, scientists, and the pharmaceutical industry work together. The Myelin Project is located at 2136 Gallows Road, Suite E, Dunn Loring, VA 22027. Their phone number is (800) 869-3546.
T.M., what you have faced and will face with your son’s devastating illness is immense. I can only tell you that the neurodegenerative diseases are no longer uniformly bleak. The team at the University of Minnesota has said, “Treatment and potential cure of [neurodegenerative] diseases, heretofore considered fatal, has become a reality during the past decade.” Whether your quest to find answers for your son results in a treatment that works for him or not, your journey of courage and love is an inspiration to us all.