Abstract
We describe a term born boy of non-consanguineous Swiss parents with tetrahydrobiopterine (BH4)-responsive Phenylketonuria (PKU) and Hirschsprung disease with unusual neonatal presentation. The child presented with floppiness, irritability, recurrent bilious vomiting and failure to pass meconium until 32 hours after birth, resulting in the clinical suspicion of an intoxication-type metabolic disease such as maple syrup urine disease (MSUD). Although the slightly elevated branched-chain amino acids in newborn screening on the fourth day of life initially supported the clinical suspicion of MSUD, the elevated Phenylalanine (Phe) of 650 µmol/L, low Tyrosine (Tyr) of 30 µmol/L, and a Phe/Tyr ratio of 22, led to the diagnosis of PKU. BH4-testing resulted in a significant decrease of Phe from 1011 to 437 µmol/L within 24 h. Urinary pterins and dihydropteridine reductase (DHPR) activity were normal, supporting the diagnosis of BH4-responsive PKU. Dietary restriction of Phe was initiated immediately, but oral feeding turned out to be difficult because of gastrointestinal symptoms. Intestinal motility disorder was suspected due to distended abdomen, obstructive symptoms and radiological findings with dilated intestinal loops and lack of intestinal gas in the anorectal region. Hirschsprung disease was confirmed by rectal suction biopsies and treated by a laparoscopically-assisted transanal pull-through (de la Torre) procedure. The boy is additionally compound heterozygous for two mutations in the phenylalanine hydroxylase (PAH) gene, which confirmed BH4-responsive PKU. It is the first case to be described in the literature of the comorbidity of PKU and Hirschsprung disease.
Highlights
Newborn screening (NBS) for phenylketonuria (PKU) was initiated in Switzerland in 1965, using the classical “Guthrie-test” [1]
Hirschsprung disease (HD) is a rare congenital birth defect of the enteric nervous system characterized by the absence of neuronal ganglia in the most distal segment of the intestine
The aganglionosis leads to an intestinal motility disorder with associated symptoms such as absence of meconium pass, abdominal distention and emesis
Summary
Newborn screening (NBS) for phenylketonuria (PKU) was initiated in Switzerland in 1965, using the classical “Guthrie-test” [1]. Clinical presentations of PKU and MSUD are very different. The aganglionosis leads to an intestinal motility disorder with associated symptoms such as absence of meconium pass, abdominal distention and emesis. It can occur as an isolated disease or as part of a multisystem disorder [8]. We are presenting an infant, with both PKU and HD in whom the symptoms of HD and slight elevations of branched-chain amino acids in newborn screening initially led to the suspicion of MSUD
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