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In the December '90 issue of the Newsletter we congratulated Sue Ann McNight for making medical history. She gave birth to a healthy 5 pound, 12 ounce baby girl on November 17, 1990. Sue Ann has classic MSUD. Following is an account of her second pregnancy as reported by her metabolic nutritionist, Sandy van Calcar from the University of Wisconsin Biochemical Genetics Clinic in Madison, Wisconsin. Sue Ann shares her own account of her struggle with Guillain-Barré Syndrome and her pregnancy and delivery of her son in the SHARING section of this issue.

As many of you know, Sue Ann McKnight is one of the oldest individuals with MSUD who has been treated since infancy. She delivered a healthy girl, Amanda, about 6 years ago and the outcome from that pregnancy was published (see references). Amanda is now in kinderarten and is doing great! Sue Ann delivered a baby boy, Blake, in March of this year [1997]. I'd like to share some of the details from this pregnancy.

Sue Ann has a higher tolerance for leucine than many individuals with classic MSUD. Because of this, she counts grams of protein rather than leucine and is allowed 29 grams of whole protein from food and whole milk which she adds to her formula. This amount of protein is equivalent to 2000 mg of leucine per day. When Sue Ann gets ill, she rarely has problems because of her MSUD. Since her last pregnancy, she suffered from metabolic acidosis only once when she developed Guillain-Barre Syndrome three years ago. (Guillain-Barré Syndrome is caused by nerve inflammation which results in progressive weakness and paralysis.)

Sue Ann presented to our clinic with her second pregnancy at 5 weeks of gestation. Her leucine level was 191 µmol/l (2.5 mg/dl). To meet her nutrition needs during pregnancy, we increased her protein equivalents from formula by adding MSUD 2 to her usual formula of Ketonex II. She also started a prenatal vitamin and extra calcium. Her leucine prescription was not changed.

During this pregnancy, Sue Ann's weight gain was normal and DNPH remained negative. We followed the same lab monitoring protocol that we developed after her first pregnancy (see Table 1). Her free carnitine in plasma decreased below 20 µmol/l at 8 weeks gestation and so carnitine was started at 20 mg/kg. During both the first and second trimester, her leucine prescription changed little (see Table 2). An increase of only 200 mg leucine in her diet increased plasma leucine above 200 µmol/l (2.6 mg/dl).

Table 1: Suggested Monitoring Protocol for Pregnant Women with MSUD*
Analyte1st & 2nd Trimester3rd Trimester
Urine ketonesDailyDaily
DNPHWeekly in the morningDaily in the morning
Amino acids (Pl & Ur)Every 2 weeksWeekly
Carnitine (Pl & Ur)MonthlyEvery 2weeks
Urine organic acidsOnce per trimesterEvery 2 weeks
AlbuminOnce per trimesterOnce per trimester
Hemoglobin & HematocritOnce per trimesterOnce per trimester
Weight gainEvery two weeksWeekly
*Assuming no signs of metabolic decompensation are noted. From reference #2
Table 2: Average Plasma amino acids and dietary intake for second pregnancy
 LeucineValineIsoleucineAverage leucine intake
µmol/lµmol/lµmol/l(mg) 
1st Trimester128143652000
2nd Trimester167206812000
3rd Trimester2883031312200
Normal values:leucine120 +/- 32 µmol/l (1.6 mg/dl)  
 valine225 +/- 50 µmol/l (2.6 mg/dl)  
isoleucine57 +/- 20 µmol/l (1.6 mg/dl)   

An ultrasound at 16 weeks of gestation showed that the baby was small but had normal development for his age. We increased her carnitine and protein equivalents from formula to see if this would improve the baby's growth. Another ultrasound at 23 weeks of gestation again showed a small baby, but normal development and growth rate. Sue Ann's metabolic labs remained within normal range.

Ultrasound at 27 weeks of gestation showed that the baby was falling from the 10 percentile for growth and a nonstress test showed decelerations, or slowed blood flow, for the baby. Sue Ann was admitted at that time for further evaluations. Her metabolic labs were again normal. We increased her whole protein intake and carnitine dose. An additional 280 mg leucine in diet increased her plasma leucine to 417 µmol/l (5.6 mg/dl).

During the two week admission, the baby was monitored daily with nonstress tests and biophysical measurements. These measurements were encouraging until 29, weeks of gestation when the tests again showed fetal decelerations with decreased tone and activity. A small pleural effusion and ascites (fluid in lung cavity) were found on ultrasound. Because of these problems, the baby was immediately delivered by C-section. He weighed 584 grams (1 pound 4.6 oz) and his length was 11 inches. Apgar scores were 3 and 7 at 1 and 5 minutes.

The baby initially required mechanical ventilation and had other problems typically associated with prematurity including bronchopulmonary dysplasia, jaundice, anemia and retinopathy. He required a neonatal ICU stay of 83 days. At discharge he weighed 4 pounds and was 16 inches in length.

Fetal growth and Sue Ann's leucine tolerance were much different with this pregnancy than with her first one. During the first pregnancy, her tolerance for leucine was much greater. At the end of the second trimester she was tolerating 3800 mg leucine compared with 2200 mg during the second pregnancy. With the first pregnancy, fetal growth delay was detected much later in pregnancy (32 weeks of gestation) and it was not as severe as with the second baby. When we detected the growth delay with her first pregnancy, we were able to gradually increase her leucine intake without causing elevated plasma leucine levels. By the end of her first pregnancy, she was taking 8600 mg of leucine per day without causing an increase in plasma levels. This was 4600 mg more than her prepregnancy tolerance!

During the first pregnancy, she also needed more carnitine to maintain normal blood levels. Her final carnitine dose was 150 mg/kg for the first pregnancy compared with a dose of 50 mg/kg for the second one. For the first pregnancy, both the increase in protein and carnitine seemed to improve the baby's growth during the final 6 weeks of pregnancy. With the second pregnancy, the baby's growth did not improve.

After her second delivery, studies of placenta tissue showed multiple small thrombosed vessels (blood clots) which were consistent with chronic ischemia (deficient blood supply). These findings could explain the baby's small growth since he likely was not receiving adequate oxygenation or nutrients. The deficient placental blood flow could also explain why Sue Ann's branch chain amino acid tolerance did not increase during the second pregnancy. Since the fetus was not receiving adequate amino acids via the placenta, Sue Ann's plasma leucine levels increased even with small increases in intake. We do not have any idea whether MSUD had a role in the development of poor placental blood flow. It seems unlikely given Sue Ann's excellent metabolic control, although conceivably, there may have been a period of high levels that we did not know about.

Blake is now 8 months old and despite the pregnancy complications, he continues to catch-up in both growth and development. We are optimistic that he will not have any long term complications from his prematurity. I know that he will have every advantage because of the great care he will receive from his parents, Sue Ann and Loni.

van Calcar S.C., Harding C.O., Davidson S.R., Barness L.A., Wolff J.A. Case reports of successful pregnancy in women with maple syrup urine disease and propionic acidemia. Am J Med Gen 44: 641-646, 1992.2.

van Calcar S.C., Wolff J.A. Nutrition Support of a pregnant woman with maple syrup urine disease. Metabolic Currents, Ross Labs 6(3): 13-18, 1993.

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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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