Lysinuric protein intolerance (LPI) is caused by mutations in the SLC7A7 gene at 14q11.2. Its clinical presentation includes failure to thrive, protein intolerance due to a secondary urea cycle defect, interstitial lung disease, renal tubulopathy, and immune disorders. Maternal uniparental disomy 14 (UPD14mat) is the most common cause of Temple syndrome (TS14), which is characterized by severe intrauterine and postnatal growth failure. Here, we describe a severe form of LPI accompanied by TS14 in an 11-month-old girl, which presented as profound failure to thrive and delayed development. LPI was diagnosed by the detection of a homozygous mutation of c.713 C>T (p.Ser238Phe) in SLC7A7, which was eventually found to co-occur with UPD14mat. Despite receiving a protein-restricted diet with citrulline and lysine supplementation, the severe failure to thrive has persisted at follow-up of the patient at 4 years of age.
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Torrents D, Mykkanen J, Pineda M, Feliubadalo L, Estevez R, de Cid R, et al. Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene. Nat Genet. 1999;21:293–6.
Borsani G, Bassi MT, Sperandeo MP, De Grandi A, Buoninconti A, Riboni M, et al. SLC7A7, encoding a putative permease-related protein, is mutated in patients with lysinuric protein intolerance. Nat Genet. 1999;21:297–301.
Koizumi A, Shoji Y, Nozaki J, Noguchi A, E X, Dakeishi M. et al. A cluster of lysinuric protein intolerance (LPI) patients in a northern part of Iwate, Japan due to a founder effect. The mass screening group. Hum Mutat. 2000;16:270–1.
Sperandeo MP, Bassi MT, Riboni M, Parenti G, Buoninconti A, Manzoni M, et al. Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance. Am J Hum Genet. 2000;66:92–9.
Ko JM, Shin CH, Yang SW, Seong MW, Park SS, Song J. The first Korean case of lysinuric protein intolerance: presented with short stature and increased somnolence. J Korean Med Sci. 2012;27:961–4.
Mauhin W, Habarou F, Gobin S, Servais A, Brassier A, Grisel C, et al. Update on lysinuric protein intolerance, a multi-faceted disease retrospective cohort analysis from birth to adulthood. Orphanet J rare Dis. 2017;12:3.
Ioannides Y, Lokulo-Sodipe K, Mackay DJ, Davies JH, Temple IK. Temple syndrome: improving the recognition of an underdiagnosed chromosome 14 imprinting disorder: an analysis of 51 published cases. J Med Genet. 2014;51:495–501.
Kagami M, Nagasaki K, Kosaki R, Horikawa R, Naiki Y, Saitoh S, et al. Temple syndrome: comprehensive molecular and clinical findings in 32 Japanese patients. Genet Med: Off J Am Coll Med Genet. 2017;19:1356–66.
Shoji Y, Noguchi A, Shoji Y, Matsumori M, Takasago Y, Takayanagi M, et al. Five novel SLC7A7 variants and y+L gene-expression pattern in cultured lymphoblasts from Japanese patients with lysinuric protein intolerance. Hum Mutat. 2002;20:375–81.
Niida Y, Ozaki M, Shimizu M, Ueno K, Tanaka T. Classification of uniparental isodisomy patterns that cause autosomal recessive disorders: proposed mechanisms of different proportions and parental origin in each pattern. Cytogenet genome Res. 2018;154:137–46.
Kotzot D, Utermann G. Uniparental disomy (UPD) other than 15: phenotypes and bibliography updated. Am J Med Genet Part A. 2005;136:287–305.
Palacin M, Bertran J, Chillaron J, Estevez R, Zorzano A. Lysinuric protein intolerance: mechanisms of pathophysiology. Mol Genet Metab. 2004;81(Suppl 1):S27–37.
Esposito V, Lettiero T, Fecarotta S, Sebastio G, Parenti G, Salerno M. Growth hormone deficiency in a patient with lysinuric protein intolerance. Eur J Pediatr. 2006;165:763–6.
Evelina M, Grazia M, Francesca O, Marta C, Paolo C, Rossella G, et al. Growth hormone deficiency and lysinuric protein intolerance: case report and review of the literature. JIMD Rep. 2015;19:35–41.
Tortora A, La Sala D, Lonardo F, Vitale M. Maternal uniparental disomy of the chromosome 14: need for growth hormone provocative tests also when a deficiency is not suspected. BMJ case Rep. 2019;12:e228662.
Beas F, Contreras I, Maccioni A, Arenas S. Growth hormone in infant malnutrition: the arginine test in marasmus and kwashiorkor. Br J Nutr. 1971;26:169–75.
Turvill JL, Mourad FH, Farthing MJ. Proabsorptive and prosecretory roles for nitric oxide in cholera toxin induced secretion. Gut. 1999;44:33–9.
We are grateful to the patient and her family for participating in this study.
EK and BHL drafted the manuscript. All authors were involved in the diagnosis and treatment of the patient. All authors read and approved the final manuscript.
This work was supported by research funds from the National Research Foundation of Korea (NRF-2018M3A9H1078335).
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from the parents of the patient regarding the reporting and publication of this case report. As it was not a clinical trial and no off-label drugs were used, ethical board approval was not necessary for this case report.
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Kang, E., Kim, T., Oh, A. et al. Lysinuric protein intolerance with homozygous SLC7A7 mutation caused by maternal uniparental isodisomy of chromosome 14. J Hum Genet 64, 1137–1140 (2019). https://doi.org/10.1038/s10038-019-0657-6