Presenter: Phyllis Acosta, DrPH, RD

The following article summarizes the informative speech given by Dr. Acosta, Director of Metabolic Diseases at Ross Products Division in Columbus, Ohio. She reviewed the most recent nutritional information relating to the health of children with MSUD. This is important information for families to discuss with their nutritionists.

Nutritional problems in the early treatment of MSUD

Before there were medical foods (formulas) for MSUD, many children died. There was no way of treating them except to restrict protein. When protein is severely restricted, children stop growing, consequently reducing their need for amino acids, since they no longer need them to make protein.

Early nutritional problems with homemade and commercial medical foods:

  • Low blood sugar- Compounds made by the patients with high keto acid levels interfered with making blood glucose.
  • Folic acid deficiency- The fat soluble vitamins were first given separately. Parents sometimes forgot to give them, so they were added to the medical foods.
  • Acidosis- This affects growth and bone mineralization. The first amino acids used in formula had hydrochloric acid attached to them, so they dissolved in liquid more readily. This caused acidosis and poor growth. (The sludge at the bottom of the bottle or cup of formula contains some of the amino acids and minerals. Be sure your child gets that sludge.)
  • Selenium deficiency- It was not known to be an essential nutrient until reported in Germany in 1975.
  • Growth retardation- It is a serious problem in MSUD and PKU. We are just starting to understand it, and it can be prevented.

The development of commercial medical foods

Between '61 and '78 clinics were mixing L-amino acids with vitamins, minerals, gelatin and some carbohydrates to make a medical food for MSUD. MSUD Diet Powder was the first commercial medical food marketed in '78. It was much lower in protein than what Dr. Acosta preferred; however, the pharmacist at the hospital where she was working refused to make the "horrible stuff" any longer when he learned a commercial medical food was available.

The first formulas had no quality assurance. Companies that make medical foods have to meet strict quality assurance. The nutrient composition must be maintained until the end of the shelf-life of that product. Quality assurance and costly ingredients, like the L-amino acids, add to the expense.

In the 80s, Scientific Hospital Supplies, a company in Europe, began marketing Analog, Maxamaid and Maxamum MSUD. In the 90s, Dr. Acosta had the pleasure of designing the products called Ketonex-1 and Ketonex-2 marketed by Ross Laboratories. Being a nutritionist and having worked with metabolic patients since the 50s, she wanted to design her own medical foods. She didn't like any of the products on the market at that time.

Deficiencies and growth problems

Reports from the 70s showed patients were not above the 25 percentile in weight or height. We are still seeing some problems with growth, some protein/energy malnutrition, and deficiencies in isoleucine, carnitine, and selenium.

Dr. Acosta showed charts of the protein and calorie intakes of children with MSUD compared with the Recommended Dietary Allowance (RDAs) and with a control group of children (average children) ages 1 to 11. Although the protein intake seemed adequate for children with MSUD according to the RDAs, it was much lower than the intake of the average child in the United States especially in the 4 to 11 age group.

A study reported in '90 involved 12 children with MSUD in the age range of 2.8 to 11 years. Their protein intake was 78% of RDAs and their calorie intake 86% of RDAs. They were shorter than normal and were selenium deficient. Selenium deficiency occurs anytime protein is restricted in the diet.

It was reported that three children with MSUD from England were significantly below normal in growth. There is a problem with the way we are feeding our children. If children are fed enough protein, they will grow normally. If we can get these children to grow normally, they will tolerate more BCAAs (branched chain amino acids). Growth in length is the best indicator of protein status.

Isoleucine deficiency makes children appear to have kwashiorkor, a severe protein-energy deficiency. Many infants with MSUD develop lesions on the buttocks, a sign of isoleucine deficiency. Unless blood is drawn every day when a clinician is trying to drop the BCAAs rapidly, it is hard to tell exactly when to start adding isoleucine. Adding isoleucine will eliminate the rash on the buttocks.

Carnitine is produced in the body but the nutrients must be provided in the diet. Studies of plasma-free carnitine levels during the pregnancy of a woman with MSUD revealed a need for larger than normal amounts of carnitine. This suggests children with MSUD may be losing carnitine because of some intermediate compounds they are making. It may be helpful to know what your child's plasma-free carnitine is.

Selenium, according to some very recent information, controls one of the enzymes in the body that changes a non-active form of thyroxine (a hormone produced by the thyroid gland) to an active form. A German report in the 70s indicated low levels of selenium in children with MSUD and PKU. In a study in Ireland, heart rhythms of PKU patients deficient in selenium became abnormal and life-threatening. In a recent study, PKU patients were given selenium. This decreased their non-active levels of thyroxine and increased the active form.

If children are not getting enough selenium, they may not have enough of the active form of thyroxine. Thyroxine can affect bone mineralization, growth and IQ. Selenium is also important for the immune system. The soil is deficient in selenium in many areas of the United States. Foods grown in those areas do not provide enough selenium.

All the medical foods made in the United States have adequate selenium. MSUD 1 and MSUD 2 are made in Germany and do not have added selenium. So if your child is taking enough of a medical food made in the United States, he/she is getting an adequate amount of selenium. The companies have to put more than normal amounts of these products in the medical foods to get normal plasma concentrations.

Studies show, however, that children with MSUD ages 1 to 4 were getting 66% of RDAs of selenium but only 20% of what a control group of children was ingesting; ages 4 to 7 were getting 53% of RDAs and only 15% of what the control group was ingesting; and ages 7 to 11 were getting 17% of RDAs but only 7% of what the control group was ingesting. This suggests that children ages 4 to 11 were not getting enough medical foods.

What are some important factors that influence the IQ of a child with MSUD? A reference by Dr. Paige Kaplan (at Children's Hospital in Philadelphia) names three possible effects: how long the child suffered the insult of high branched chain keto acids before diagnosis, the long term metabolic control (how tightly the diet is controlled), and possibly the metabolic control at the time the test was done.

Recommendations for providing adequate nutrition

  1. The protein in medical foods is an artificial form of protein. The amino acids are in their free form (like in meat already broken down by the digestive tract) and they are quickly absorbed. Because the amino acids are absorbed faster than the body can manufacture its own protein from them, the amino acid - after the amino group is removed - is used for energy purposes and not as a building block for protein.

    So we have to give the children more amino acids and feed them more frequently - four to eight times daily. It is not a good practice to give the medical food only in the morning and evening. Spread it out during the day and give some natural protein with the medical food. You wouldn't give your "normal" children all their food for the day at one time.
  2. The three BCAAs are not in the same proportion as in natural protein (from foods). Leucine is higher than isoleucine and valine. Therefore, children with MSUD can become deficient in isoleucine and valine. By adding the pure isoleucine and valine to the medical food, you can enhance growth and prevent low levels of these two amino acids.
  3. It is important that everything prescribed be ingested each day. Dietitians make parents very compulsive because it is important.
  4. Certain things need to be monitored: nutrient intake, growth, plasma amino acids, albumin, and ferritin - an indication of iron status. If the medical food given does not contain selenium, a supplement needs to be given every day.

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