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


As our legislators headed home for their August break, Rare Disease Legislative Advocates got busy.

Read More

MSUD Advocacy Update

Healthcare and issues facing the rare disease community have been at the forefront of national conversations over the past 6 months.

Read More

I want to help out, but I don’t know how

Have you ever wanted to help out the MSUD Family Support Group but were unsure about how to contribute? The MSUD Family Support Group is actively looking for volunteers to assist with advocacy and fundraising efforts.

Read More

From The Editor

Hello to my MSUD family! The power of this family hit home this summer, when Hannah (Classic MSUD age 23 years) and I visited Israel.

Read More


In the 2016 survey of the membership of the MSUD Family Support Group, research for improved treatments and potential cure was rated “most important” by 90% of the responding members.

Read More

MSUD Awareness Day

Now more than ever before we are hearing about National Awareness Days which are set by organizations or the government to bring attention to issues of importance.

Read More


A Child's Life

Subscribe to our mailing list

Signup To Our Newsletter Signup with your email address to receive news and updates