Neonatal MSUD Metabolic Crisis - to Dialyse or Not to Dialyse?

Background: Maple Syrup Urine Disease (MSUD), an inborn error of metabolism, is caused by defects in the branched-chain α-ketoacid dehydrogenase complex. Clinical presentation in untreated patients includes accumulation of branched-chain amino acids (BCAAs) leucine (Leu), isoleucine (Ile) and Valine (Val), within the first 12-24 hours of life. Conventional methods of lowering high plasma BCAAs include peritoneal dialysis (PD), hemodialysis (HD), continuous renal replacement therapy (CRRT) and continuous veno-venous hemofiltration (CVVH). These may not be viable in premature neonates due to low body weight and unstable conditions.

Case Report: Patient 1(m)- born week 38, birth weight (BW) 4300 g; positive results for MSUD. Leu levels were elevated; HD was initiated. Levels dropped by 58% and he started enteral feeds (BCAA-free metabolic formula). Following HD, Patient 1 underwent CVVH, and Leu decreased another 25%. By day 8, 100% of total protein and 70% of total energy goals were reached. Leu continued to normalize, and on day 14 breastmilk (intact protein) was added; Patient 1 reached 100% of total protein and energy requirements.

Fraternal twins born week 34; Patient 2(m)- BW 1650g, Patient 3(f)- BW 1840g; positive results for MSUD. Leu levels were elevated and enteral feeds stopped due to bloody stools. BCAA-free TPN solution was not available. Patients’ weights were too low and conditions too unstable for conventional dialysis; several courses of double volume exchange transfusion (DVET) were initiated instead. After 5 courses, Leu levels dropped by 70-74%. Patient 2`s Leu levels normalized on day 19, and Patient 3’s on day 23; cow milk-based formula (intact protein) was added. Patients reached 100% of total protein and energy goals by day 30.

Conclusion: Leucine normalization following MSUD diagnosis in premature infants using DVET was prolonged when compared to standard methods. As a result, patients were delayed in reaching 100% of nutritional requirements.