Referring Physicians

INFORMATION:

At the present time, patients may be referred for evaluation of:

  1. Glut-1 DS (glucose transporter type-1 deficiency syndrome)
  2. MELAS (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes)
  3. MERRF (mitochondrial encephalomyopahy with ragged-red fibers)
  4. Pyruvate dehydrogenase deficiency
  5. Pyruvate carboxylase deficiency
  6. Ion channel disorders
  7. Genetic and metabolic encephalopathies of unknown origin
  8. Genetic and metabolic myopathies of unknown origin

There may be fees associated with the evaluation.

Upon review of this information, if warranted, further documentation and blood samples of the patient and immediate relatives may be requested. None of the items received will be returned. Therefore, only copies should be provided.

A. GENERAL REFERRALS (EXCLUDING Glut-1 DS)

All referrals must be made using the following forms and signed by patients and/or parents and the referring physician. They should be sent via regular mail to the address listed below. Please read the form instructions and conditions carefully.

Download Physician Referral form (do not use for Glut-1 DS) [MS Word File | PDF File]


B. Glut-1 DS REFERRALS

Prior contact with us is required. No documents or samples will be accepted without our prior approval. Please call either the lab or one of the coordinators listed below before sending any information. After contact has been made and approval acquired, referrals may be sent via regular mail or electronically to the address listed below. Please read the forms instructions and conditions carefully.

Download Physician Referral form (Glut-1 DS only) [MS Word File | PDF File]


Contact Information:

Colleen Giblin Laboratories
Columbia University Medical Center
College of Physicians and Surgeons (P&S), Room 5-443
630 W. 168 Street
New York, NY 10032

Laboratory phone:

212-305-8245

Laboratory fax:

212-305-0431

Clinical Coordinator:

Kristin Engelstad
Phone: 212-305-6834 || Fax: 212-342-2893
E-mail: ke4@columbia.edu

Current Studies

MELTIMI (MELAS Trial of Idebenone using MRS)

Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS)

Study Purpose:
Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes (MELAS) is a multi-system disorder that can cause exercise intolerance, migraines, gastrointestinal issues, memory loss, seizures and strokes. MELAS is caused by a mutation in mitochondrial DNA. The most common mitochondrial mutation causing MELAS is the A3243G mutation. The purpose of this clinical trial is to determine whether a medication called Idebenone has an effect on brain lactate as measured by magnetic resonance spectroscopy (MRS). MRS is done in an MRI scanner, and is safe and typically well tolerated. An additional goal is to study the safety and tolerability of Idebenone in people with MELAS.

Idebenone:
Idebenone is thought to improve energy production in mitochondria, the powerhouses of the cell. It is also thought to defend against free radicals that can cause damage in mitochondrial disease. It has improved neurological function in other mitochondrial diseases such as Friedreich’s ataxia. The study drug is an experimental medication, and it is hoped that this trial will be a first step towards approval by the Food and Drug Administration (FDA), a prerequisite for making it available to patients in this country.

Study Type: Clinical Trial

Official Title: MELTIMI Study (Idebenone and MELAS)

Estimated Enrollment: 21

Study Start Date: May 2009

Eligibility:

Inclusion Criteria

  • Ages: 8 to 64 years old
  • Gender: male and female
  • Genetic requirement: carrier of A3243G mitochondrial DNA mutation
  • Body Weight: at least 82 pounds

Exclusion Criteria (not eligible to participate)

  • Unable to have MRS (choclear implant, inability to lie still for 45 minutes, etc)
  • Patient is pregnant
  • Use of Idebenone at any dose, or CoQ10 at more than 100mg/day within a 1 month period prior to baseline
  • Clinically significant laboratory abnormalities (study doctor will determine)
  • Use of other clinical trial investigational drugs within a 1 month period prior to baseline

Study Medication:

  • Participants will be randomized to one of two doses of Idebenone or to placebo ( a pill that looks like Idebenone but contains no Idebenone)
  • Participants will take the study medication (Idebeonone or placebo) for 1 month.
  • In other disease, Idebenone has been safe and well tolerated.

Time and Travel Commitment:

  • Take study medication for 1 month
  • Participants will travel to NYC 2-3 times over a period of 14 weeks for research visit
  • Reimbursement for transportation and hotel will be provided

Contacts and Locations:

Kris Engelstad, Study Coordinator
Phone: 1-212-305-6834
E-mail: ke4@columbia.edu; melas@columbia.edu
Location: Columbia University Medical Center
Clinical Research Center for Mitochondrial Disorders
The Neurological Institute
710 W. 168th St, Box 68
New York, NY 10032

Publications: Our publications regarding MELAS are located in the “Publications” section of this website.

» download consent form. This consent form is solely for information to help you decide whether you want to participate in the MELTIMI study. Should you choose to participate, you will be requested to sign and date a current consent form, which may be slightly different than the consent shown here.


MELAS

Natural History Study – Mitochondrial Encephalomyopathies Associated with MtDNA Point Mutations

Status:

Open for Enrollment

Mitochondrial and Mental Retardation: Investigations of Clinical Syndromes Associated with MtDNA Point Mutations

The Natural History Study is an ongoing study that involves participants that have point mutations in mitochondrial DNA (mtDNA). These mutations affect the genetic material contained in the mitochondria of the cell. Mitochondria, often called the “powerhouse” of the cell, are small structures within cells that provide the energy necessary to power growth and change over time. The purpose of this study is to better characterize mitochondrial disorders as they present over time in participants. Through this study we hope to determine whether mtDNA point mutations produce any measurable disturbances of thinking, attention, intelligence, behavior, or neurological functioning. Eligible participants must have a proven mitochondrial point mutation. Some or all participants may represent members of a single family because mtDNA point mutations are inherited from one’s mother. Fathers and other paternal family members may also be invited to participate as control subjects.

Subjects are asked to return to our center, usually on a yearly basis, for ongoing evaluation and comprehensive care.

Study Team:

Contact Kris Engelstad (ke4@columbia.edu)


GLUT-1

Natural History Study – Neuroglycopenia: Glut-1 Deficiency Syndrome (GLUT-1 DS)

Status:

Open for Enrollment

Neuroglycopenia, also known as GLUT-1 Deficiency Syndrome (Glut-1 DS), is a disorder that interferes with the functioning of glucose transport proteins. These proteins are responsible for transporting glucose into the brain from the blood. When these transport proteins are not working properly, decreased amounts of glucose are available to the brain. Because glucose is the primary essential fuel for the developing brain, inadequate supplies of it can result in physical and cognitive difficulties. The purpose of this study is to examine the nature of these difficulties. Through this study we hope to determine the types of DNA mutations that cause this disease, how the glucose transporters are affected, and how the brain responds to these mutations. We plan to do this by studying the brain’s electrical activity, structure, and function. In this study we will evaluate language skills, attention, behavior, and neurological functioning. Eligible participants in this study are suspected of having neuroglycopenia.

Subjects are asked to return to our center, usually on a yearly basis, for ongoing evaluation and comprehensive care.

Study Team:

Contact Kris Engelstad (ke4@columbia.edu)

Glut-1 DS

What is Glut- Deficiency Syndrome (Glut-1 DS)

Disease characteristics:

Glucose transporter type 1 deficiency syndrome (Glut1-DS) is characterized by infantile seizures refractory to anticonvulsants, followed by deceleration of head growth, delays in mental and motor development, spasticity, ataxia, dysarthria, opsoclonus, and other paroxysmal neurologic phenomena, often occurring prior to meals. Affected infants appear normal at birth following an uneventful pregnancy and delivery. Birth weight and Apgar scores are normal. Seizures usually begin between age one and four months. Apneic episodes and abnormal episodic eye movements simulating opsoclonus may precede the onset of seizures by several months. Five seizure types occur: generalized tonic or clonic, myoclonic, atypical absence, atonic, and unclassified. The frequency of seizures varies among affected individuals. Varying degrees of cognitive impairment, ranging from learning disabilities to severe mental retardation, are characteristic.

Diagnosis/testing

The diagnosis of Glut1-DS is established in neurologically impaired individuals with 1) reduced cerebrospinal fluid (CSF) glucose concentration (hypoglychorrhachia) 2) low ratio of CSF glucose concentration to blood glucose concentration. Molecular genetic testing is available on a clinical basis.

» Current Clinical Studies

Research

LABORATORY & CLINICAL RESEARCH:

Laboratory Research

a. Molecular basis of cerebral energy utilization and failure

The Colleen Giblin Laboratories, in the context of the Division of Pediatric Neurology at the Columbia University Medical Center, enjoy a distinguished tradition of metabolic disease research and discovery. The Laboratories and the Division also remain at the forefront of investigative and clinical excellence in other areas such as sickle cell encephalopathy, pediatric brain tumors, pediatric epilepsy, storage diseases, fetal neurotoxicity and functional neuroimaging. Diseases like Reye syndrome, glucose transporter deficiency (Glut-1 DS), carnitine deficiency, pyruvate dehydrogenase deficiency and pyruvate carboxylase deficiency, among other mitochondrial disorders, were first identified/treated by members of the Division.

An unusually large patient base comprising referrals from every part of the world is available for metabolic research. A tissue culture bank containing some 1,000 samples with accompanying clinical descriptions has been established by Dr. De Vivo and constitutes a unique investigational resource.

Our efforts are currently devoted to the central steps of energy metabolism and integrate molecular and clinical aspects, a research paradigm that will be adopted by most institutions in the future.

Projects include:

  1. The molecular genetics, pathogenesis, diagnosis and therapy of Glut-1 DS. The Laboratories serve as the major referral center for diagnosis and mutation identification in the world and carry out natural history studies and therapeutic trials.
  2. Pyruvate dehydrogenase function, regulation, and deficiency. The identification of modulatory genes involved in the function of this crucial metabolic process, aided by the molecular study of patients and families with uncommon forms of pyruvate dehydrogenase deficiency, is under way.
  3. The molecular genetics, pathogenesis and clinical forms of Pyruvate carboxylase deficiency.
  4. The natural history and therapy of the syndrome of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS), a prototype mitochondrial disease.

Patients participating in these NIH-sponsored research projects travel to the site of our laboratories and take part in functional brain imaging and neuropsychological assessment techniques, as well as other research related study procedures being developed in conjunction with the Laboratories.

b. Molecular excitability disorders

This research program was developed in response to the great expansion and renewed attention these disorders have experienced since the advent of molecular genetics and the patch clamp, two major tools used in combination at the Laboratories. Diseases of interest include epilepsy, arrhythmia, genetic myopathies and neurotoxicity.

The Giblin Laboratories add the expertise of scientists interested in ion channel structure, function and pharmacological modification to the well-established tradition of clinical study and discovery of excitability disorders of muscle, nerve, and brain at the Neurological Institute.


Clinical Research

The clinical aspect of this research program benefits from the availability of the Irving Institute for Clinical and Translational Research, an NIH-funded investigational resource where patients and their families are studied and followed. Patients are also seen at our affiliated space in the Spinal Muscular Atrophy Clinical Research Center. Involvement of basic and clinical researchers in group discussions of patient assessment and management is strongly encouraged, in order to cross-fertilize participating scientists and clinicians and to nurture the exchange of ideas from all traditional disciplines. Opportunities for interaction with other groups interested in excitability from molecular, cellular, systems or cognitive perspectives are emphasized.
» NHS Study
» Glut-1 Study