George Mazariegos, MD
Children’s Hospital of Pittsburgh

Dr. Mazariegos treated attendees to an exciting update on liver transplantation as a treatment option for MSUD.

Medical therapy and transplant both carry risk. For the individual with MSUD, metabolic decompensation is always a possibility. As Dr. Mazariegos noted, the highly restrictive nature of the diet affects quality of life, and the cost of formula and low protein foods can be prohibitive for many. Transplant not only carries risks for potential complications rejection and the need for immunosuppression. The extent to which these latter risks can be minimized is a critical factor in the decision whether or not to transplant.

Liver transplant is a treatment choice for a number of disease states in addition to metabolic disease, including malignancy, alcoholism, biliary atresia, and hepatitis. Data on survival outcome based on diagnosis, though, have shown that survival rates are highest for those with metabolic disease.

Thus far, 19 MSUD patients, ages 1.7 to 32 years, have undergone transplant. The first was a girl exhibiting vitamin A toxicity. After her transplant, her amino acid levels normalized without dietary restrictions. Subsequently, an additional 18 MSUD Patients (classic variant) were transplanted under elective protocol as described between 5/30/2004-5/31/2006.

While there have been complications post-transplant, all transplantees have survived and have normal liver function. A number of patients have experienced liver rejection, steroid sensitivity, and viral infections, however all have done well with medical and surgical treatment. Patients have experienced normal branched chain amino acid levels immediately post transplant, with maintenance of metabolic stability under conditions of unrestricted protein intake as well as inter-current illnesses. In addition to the obvious medical benefits, subjective improvements have been noted in attention span, speech, behavior and motor skills.

Historically, the heavy doses of immunosuppressive drugs required long term has had a significant impact on quality of life post-transplant. Cyclosporin, for example, causes excessive hair growth, weight gain, high blood pressure and bone disease. The ability to taper and, ideally, to withdraw immunosuppressive medications while continuing to prevent rejection is the ultimate goal. Tacrolimus, a newer class of drug, is moving treatment in that direction.

Variability in immune function allows some patients to be more successful than others in reducing their dependency on immunosuppressive drugs. Currently 28% of selected long term liver transplantees have been able to remain drug-free. It is hoped that an evaluation of the characteristics of these patients may allow others to achieve drug-free status.

The group hopes to develop an MSUD transplant registry to allow tracking of all who undergo this procedure. Sequential neuro-developmental evaluations are also planned to elucidate improvements which may be occurring in this area. The ability to transplant the MSUD patient’s liver into a non-MSUD patient (domino transplant) without transferring MSUD will benefit others as well.

Dr. Mazariegos suggests that individuals with MSUD and their parents consider the following potential indications for transplant:
  • Lability of the disease despite optimal medical control and the development of metabolic crisis
  • Neuro-developmental sequalae:
    • Attention deficits, hyperactivity in children
    • generalized anxiety and panic attacks, depression, delay in adults
    • Potential for cerebral edema
  • Dependency on medical enteral formulation
  • Intensiveness of medical therapy compared to post transplant therapy
Dr. Mazariegos acknowledges the assistance of his colleagues: H. Morton, K. Strauss, R Squires, J. Vockely, D. Finegold, M. Virji, L. Cropcho, W. McGhee, L. Seward, K.Soltys, G. Bond, R. Sindhi

Children’s Hospital of Pittsburgh,
Clinic for Special Children, Strasburg, PA
University of Pittsburgh Medical Center and the
Thomas E. Starzl Transplantation Institute


The MSUD Family Support Group is currently funding several research projects and we are proactively looking for researchers interested in developing new treatments or finding a cure for MSUD. Significant funding is necessary if we are to accomplish this goal.
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