Born at 27 weeks of Gestation with Classical PKU: Challenges of Dietetic Management in a very Preterm Infant

Abstract

Few cases of premature infants with classical phenylketonuria (PKU) have been reported. Treatment of these patients is challenging due to the lack of a phenylalanine (Phe)-free amino acid (AA) solution for parenteral nutrition. A boy born at 27 weeks of gestation with a weight of 1000 g was diagnosed with classical PKU on day 7 because of highly elevated Phe level at newborn screening (2800 µmol/L). Phe intake was suspended for 5 days and during this time intravenous glucose and lipids as well as small amounts of Phe-free formula through nasogastric tube were given. Because of insufficient weight gain attributable to deficiency of essential AA, a Phe-reduced, BCAA-enriched parenteral nutrition was added to satisfy AA requirements without overloading in Phe. Under this regimen, the boy started to gain weight, Phe plasma levels progressively reduced and normalized on day 19. At the age of 40 months, the patient shows normal growth parameters (height 25th percentile, weight 25–50th percentile, head circumference 50th percentile) with a normal result for formally tested psychomotor development (WPPSI-III). The good outcome of the patient in spite of over 2 weeks of extremely high Phe concentrations suggests that the premature brain may still have enough plasticity to recover. Lacking a Phe-free intravenous AA solution, successful management of premature infants with PKU depends on the child's tolerance of enteral nutrition. Although the coincidence of PKU and prematurity is rare, there is strong need for the development of an appropriate Phe-free amino acid solution for parenteral nutrition especially in case of gastro-intestinal complications of prematurity.

The complete European guidelines on phenylketonuria: diagnosis and treatment

“…Infants, particularly those who are premature, and young children requiring long-term parenteral nutrition, are likely to be at risk from permanent damage if blood Phe concentrations cannot be controlled. Single case studies of premature infants with PKU given standard preparations of amino acid intravenous solutions for limited periods have had very high blood Phe levels although apparently without adverse effects on long-term neurological outcome [ 312 – 314 ]. A specially prepared Phe-free intravenous amino acid solution has been used in a 6 year old with PKU with an intra-abdominal malignancy, which effectively prevented high Phe levels [ 315 ].…”

“…A specially prepared Phe-free intravenous amino acid solution has been used in a 6 year old with PKU with an intra-abdominal malignancy, which effectively prevented high Phe levels [ 315 ]. A commercially available preparation with a lower content of branched chain amino acids designed for use in hepatic failure was used in a premature infant with PKU as this preparation also contained less than usual Phe [ 312 ] and in a child with a facial tumour [ 316 ]. However elevated Phe levels could not be completly prevented in these cases.…”

Extremely low birthweight neonates with phenylketonuria require special dietary management

“…With a birth rate around 110,000 neonates per year in our country of 10.5 million inhabitants, and a detection rate of positive neonatal screening for PKU of one per 5500 neonates, the chance of an infant having an ELBW and PKU is 1.7 per million. This explains why clinicians have limited experience of caring for ELBW neonates with PKU 1,5,6 . Untreated PKU can cause severe intellectual disability, epilepsy, attention deficit disorders and behavioural problems that begin in early infancy 6,7 .…”

“…The average incidence of PKU in Europe is approximately one in 10,000 live births 4 . The combination of both ELBW and PKU is very rare and most perinatology centres and, or, specialised PKU centres only have limited experience of nutrition in such cases 1,5,6 …”

“…Premature neonates with an extremely low birthweight (ELBW) under 1000 grams need a high protein diet so that they can achieve adequate catch‐up of postnatal growth and prevent growth failure 1 . This is usually achieved with parenteral solutions of essential amino acids or enteral feeding with human milk supplemented with bovine or human milk‐based fortifiers 2 .…”