Hyperexcretion of homocitrulline in a Malaysian patient with lysinuric protein intolerance.
Lysinuric protein intolerance (LPI; MIM 222700) is an inherited aminoaciduria with an autosomal recessive mode of inheritance. Biochemically, affected patients present with increased excretion of the cationic amino acids: lysine, arginine, and ornithine. We report the first case of LPI diagnosed in Malaysia presented with excessive excretion of homocitrulline. The patient was a 4-year-old male who presented with delayed milestones, recurrent diarrhea, and severe failure to thrive. He developed hyperammonemic coma following a forced protein-rich diet. Plasma amino acid analysis showed increased glutamine, alanine, and citrulline but decreased lysine, arginine and ornithine. Urine amino acids showed a marked excretion of lysine and ornithine together with a large peak of unknown metabolite which was subsequently identified as homocitrulline by tandem mass spectrometry. Molecular analysis confirmed a previously unreported homozygous mutation at exon 1 (235 G > A, p.Gly79Arg) in the SLC7A7 gene. This report demonstrates a novel mutation in the SLC7A7 gene in this rare inborn error of diamino acid metabolism. It also highlights the importance of early and efficient treatment of infections and dehydration in these patients.


CONCLUSIONS
The diagnosis of LPI is usually not suspected by clinical findings alone, and specific laboratory investigations and molecular analysis are important to get a definitive diagnosis.
Biochemistry Unit, Specialised Diagnostic Centre, Institute for Medical Research, Jalan Pahang, 50588 Kuala Lumpur, Malaysia. anasufiza@imr.gov.my
Anasufiza
A
Habib
Zabedah
Z
Md Yunus
Nor Azimah
NA
Azize
Gaik-Siew
GS
Ch'ng
Winnie Peitee
WP
Ong
Bee-Chin
BC
Chen
Ho-Torng
HT
Hsu
Ke-Juin
KJ
Wong
James
J
Pitt
Lock-Hock
LH
Ngu
D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D027241:Amino Acid Transport System y+L; D015415:Biomarkers / Q000652:urine; D002675:Child, Preschool; D002956:Citrulline / Q000031:analogs & derivatives* / Q000652:urine; D027301:Fusion Regulatory Protein 1, Light Chains / Q000235:genetics*; D005819:Genetic Markers; D005820:Genetic Testing; D006801:Humans; D008296:Malaysia; D008297:Male; D017354:Point Mutation
D027241:Amino Acid Transport System y+L; D015415:Biomarkers; D027301:Fusion Regulatory Protein 1, Light Chains; D005819:Genetic Markers; C421261:SLC7A7 protein, human; C001352:homocitrulline; D002956:Citrulline