Lysinuric protein intolerance. Urinary amino acid excretion at 2 and 9 days of age

Lysinuric protein intoleance (LPI; McKusick) is an inborn metabolic error consisting of defective cationic amino acid transport. Urinary lysine (LYS), arginine (ARG), and ornithine (ORN) are increased despite low plasma concentrations. This transport defect results in a deficiency in an essential amino acid, LYS, and two intermediates in the urea cycle: ARG and its 'backbone' ORN. Clinical symptoms include episodic hyperammonaemia (Simell 1989). We now report a case of LPI diagnosed very early in a newborn with a family history of this disorder. Urinary amino acid analyses were started at 2 days of age, allowing observation of the modifications in amino acid excretion over 1 week, and comparison with concentrations at the age of 9 months. Nabil D. was born of consanguineous parents (first cousins) of Tunisian origin at 36-37 weeks of pregnancy. He was hospitalized in the Paediatrics Unit for surveillance of low birth weight (2170g). Physical examination at admission was normal. The child was breast-fed and gained weight regularly. The hospital stay was marked by jaundice with a bilirubin concentration that rose to 145 mg/L on day 7, then decreased the following days in response to treatment. The only other finding was a transient and moderate elevation in transaminases and LDH. Nabil is the third child in his family; he has a brother 7 years old in whom LPI was diagnosed, and a younger sister without this disorder. In light of the family history, chromatography of the urinary amino acids was initiated at 2 days of age. Increased excretion was noted for taurine, citrulline, 31 #mol/mmol creatinine (normal < 10); lysine, 370 #mol/mmol creatinine (normal 45-190); especially arginine, 86/~mol/mmol creatinine (normal 0-14); and, to a lesser degree, ornithine, 35 #mol/mmol creatinine (normal 0-20). One week later (age 9 days), chromatography of plasma amino acids failed to reveal any elevations in glutamate-glutamine, 945 #mol/L (normal 900 + 340), but increases were noted in both asparagine, 160 #mol/L (normal 48 _ 10), and citrulline, 65#mol/L (normal 16 _+ 5). Arginine was more or less normal, 50#mol/L (normal 67 _ 14). Lysine, 66#mol/L (normal 180 _+ 32), and ornithine, 10#mol/L (normal 7 7 _ 27), were low. Ornithine excretion was elevated at this time, 64~mol/mmol creatinine; lysine excretion reached 580 #mol/mmol creatinine, and arginine excretion was very high, 210 #mol/mmol creatinine. The boy was followed up regularly at the outpatient clinic. At 3 4 weeks, his