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Neutral hyperaminoaciduria

MedGen UID:
344676
•Concept ID:
C1856194
•
Finding
HPO: HP:0008353

Definition

The presence of an abnormally increased concentration of neutral amino acids in the urine. The neutral amino acids are tryptophan, alanine, asparagine, glutamine, histidine, isoleucine, leucine, phenylalanine, serine, threonine, tyrosine and valine. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVNeutral hyperaminoaciduria

Conditions with this feature

Neutral 1 amino acid transport defect
MedGen UID:
6723
•Concept ID:
C0018609
•
Disease or Syndrome
Hartnup disorder (HND) is characterized by transient manifestations of pellagra, cerebellar ataxia, and psychosis. It is caused by impaired transport of neutral amino acids across epithelial cells in renal proximal tubules and intestinal mucosa (summary by Kleta et al., 2004).
See: Condition Record
Neutral 1 amino acid transport defect

Professional guidelines

PubMed

Overview of symptoms and treatment for lysinuric protein intolerance.
Noguchi A, Takahashi T
J Hum Genet 2019 Sep;64(9):849-858. Epub 2019 Jun 18 doi: 10.1038/s10038-019-0620-6. PMID: 31213652
Molecular genetic characterization of cblC defects in 126 pedigrees and prenatal genetic diagnosis of pedigrees with combined methylmalonic aciduria and homocystinuria.
Hu S, Mei S, Liu N, Kong X
BMC Med Genet 2018 Aug 29;19(1):154. doi: 10.1186/s12881-018-0666-x. PMID: 30157807Free PMC Article
The complete European guidelines on phenylketonuria: diagnosis and treatment.
van Wegberg AMJ, MacDonald A, Ahring K, Bélanger-Quintana A, Blau N, Bosch AM, Burlina A, Campistol J, Feillet F, Giżewska M, Huijbregts SC, Kearney S, Leuzzi V, Maillot F, Muntau AC, van Rijn M, Trefz F, Walter JH, van Spronsen FJ
Orphanet J Rare Dis 2017 Oct 12;12(1):162. doi: 10.1186/s13023-017-0685-2. PMID: 29025426Free PMC Article

Recent clinical studies

Etiology

The Phenotypic and Mutational Spectrum of the FHONDA Syndrome and Oculocutaneous Albinism: Similarities and Differences.
Kruijt CC, Gradstein L, Bergen AA, Florijn RJ, Arveiler B, Lasseaux E, Zanlonghi X, Bagdonaite-Bejarano L, Fulton AB, Yahalom C, Blumenfeld A, Perez Y, Birk OS, de Wit GC, Schalij-Delfos NE, van Genderen MM
Invest Ophthalmol Vis Sci 2022 Jan 3;63(1):19. doi: 10.1167/iovs.63.1.19. PMID: 35029636Free PMC Article
Glycomacropeptide: long-term use and impact on blood phenylalanine, growth and nutritional status in children with PKU.
Daly A, Evans S, Chahal S, Santra S, Pinto A, Jackson R, Gingell C, Rocha J, Van Spronsen FJ, MacDonald A
Orphanet J Rare Dis 2019 Feb 15;14(1):44. doi: 10.1186/s13023-019-1011-y. PMID: 30770754Free PMC Article
Carbohydrate status in patients with phenylketonuria.
Couce ML, Sánchez-Pintos P, Vitoria I, De Castro MJ, Aldámiz-Echevarría L, Correcher P, Fernández-Marmiesse A, Roca I, Hermida A, Martínez-Olmos M, Leis R
Orphanet J Rare Dis 2018 Jun 27;13(1):103. doi: 10.1186/s13023-018-0847-x. PMID: 29945661Free PMC Article
Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China.
Liu N, Huang Q, Li Q, Zhao D, Li X, Cui L, Bai Y, Feng Y, Kong X
BMC Med Genet 2017 Oct 5;18(1):108. doi: 10.1186/s12881-017-0467-7. PMID: 28982351Free PMC Article
State of the art in muscle lipid diseases.
Liang WC, Nishino I
Acta Myol 2010 Oct;29(2):351-6. PMID: 21314018Free PMC Article

Diagnosis

Genetic etiology and clinical challenges of phenylketonuria.
Elhawary NA, AlJahdali IA, Abumansour IS, Elhawary EN, Gaboon N, Dandini M, Madkhali A, Alosaimi W, Alzahrani A, Aljohani F, Melibary EM, Kensara OA
Hum Genomics 2022 Jul 19;16(1):22. doi: 10.1186/s40246-022-00398-9. PMID: 35854334Free PMC Article
The phenylketonuria patient: A recent dietetic therapeutic approach.
Manta-Vogli PD, Dotsikas Y, Loukas YL, Schulpis KH
Nutr Neurosci 2020 Aug;23(8):628-639. Epub 2018 Oct 25 doi: 10.1080/1028415X.2018.1538196. PMID: 30359206
Molecular genetic characterization of cblC defects in 126 pedigrees and prenatal genetic diagnosis of pedigrees with combined methylmalonic aciduria and homocystinuria.
Hu S, Mei S, Liu N, Kong X
BMC Med Genet 2018 Aug 29;19(1):154. doi: 10.1186/s12881-018-0666-x. PMID: 30157807Free PMC Article
The complete European guidelines on phenylketonuria: diagnosis and treatment.
van Wegberg AMJ, MacDonald A, Ahring K, Bélanger-Quintana A, Blau N, Bosch AM, Burlina A, Campistol J, Feillet F, Giżewska M, Huijbregts SC, Kearney S, Leuzzi V, Maillot F, Muntau AC, van Rijn M, Trefz F, Walter JH, van Spronsen FJ
Orphanet J Rare Dis 2017 Oct 12;12(1):162. doi: 10.1186/s13023-017-0685-2. PMID: 29025426Free PMC Article
Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China.
Liu N, Huang Q, Li Q, Zhao D, Li X, Cui L, Bai Y, Feng Y, Kong X
BMC Med Genet 2017 Oct 5;18(1):108. doi: 10.1186/s12881-017-0467-7. PMID: 28982351Free PMC Article

Therapy

Nutrition in phenylketonuria.
Talebi S, Eshraghi P
Clin Nutr ESPEN 2024 Dec;64:307-313. Epub 2024 Oct 19 doi: 10.1016/j.clnesp.2024.09.032. PMID: 39427751
Genetic etiology and clinical challenges of phenylketonuria.
Elhawary NA, AlJahdali IA, Abumansour IS, Elhawary EN, Gaboon N, Dandini M, Madkhali A, Alosaimi W, Alzahrani A, Aljohani F, Melibary EM, Kensara OA
Hum Genomics 2022 Jul 19;16(1):22. doi: 10.1186/s40246-022-00398-9. PMID: 35854334Free PMC Article
Fluctuations in phenylalanine concentrations in phenylketonuria: a review of possible relationships with outcomes.
Cleary M, Trefz F, Muntau AC, Feillet F, van Spronsen FJ, Burlina A, Bélanger-Quintana A, Giżewska M, Gasteyger C, Bettiol E, Blau N, MacDonald A
Mol Genet Metab 2013 Dec;110(4):418-23. Epub 2013 Sep 9 doi: 10.1016/j.ymgme.2013.09.001. PMID: 24090706
Large neutral amino acids supplementation in phenylketonuric patients.
Rocha JC, Martel F
J Inherit Metab Dis 2009 Aug;32(4):472-80. Epub 2009 May 13 doi: 10.1007/s10545-009-1132-x. PMID: 19437129
Phenylketonuria: tyrosine beyond the phenylalanine-restricted diet.
van Spronsen FJ, Smit PG, Koch R
J Inherit Metab Dis 2001 Feb;24(1):1-4. doi: 10.1023/a:1005689232358. PMID: 11286377

Prognosis

The Phenotypic and Mutational Spectrum of the FHONDA Syndrome and Oculocutaneous Albinism: Similarities and Differences.
Kruijt CC, Gradstein L, Bergen AA, Florijn RJ, Arveiler B, Lasseaux E, Zanlonghi X, Bagdonaite-Bejarano L, Fulton AB, Yahalom C, Blumenfeld A, Perez Y, Birk OS, de Wit GC, Schalij-Delfos NE, van Genderen MM
Invest Ophthalmol Vis Sci 2022 Jan 3;63(1):19. doi: 10.1167/iovs.63.1.19. PMID: 35029636Free PMC Article
Genetic causes of nystagmus, foveal hypoplasia and subnormal visual acuity- other than albinism.
Ehrenberg M, Bagdonite-Bejarano L, Fulton AB, Orenstein N, Yahalom C
Ophthalmic Genet 2021 Jun;42(3):243-251. Epub 2021 Feb 17 doi: 10.1080/13816810.2021.1888128. PMID: 33594928
Overview of symptoms and treatment for lysinuric protein intolerance.
Noguchi A, Takahashi T
J Hum Genet 2019 Sep;64(9):849-858. Epub 2019 Jun 18 doi: 10.1038/s10038-019-0620-6. PMID: 31213652
Food triggers and inherited metabolic disorders: a challenge to the pediatrician.
Maines E, Di Palma A, Burlina A
Ital J Pediatr 2018 Jan 25;44(1):18. doi: 10.1186/s13052-018-0456-2. PMID: 29368648Free PMC Article
Lysinuric protein intolerance (LPI): a multi organ disease by far more complex than a classic urea cycle disorder.
Ogier de Baulny H, Schiff M, Dionisi-Vici C
Mol Genet Metab 2012 May;106(1):12-7. Epub 2012 Feb 17 doi: 10.1016/j.ymgme.2012.02.010. PMID: 22402328

Clinical prediction guides

The clinical, pathological, and genetic characteristics of lipid storage myopathy in northern China.
Han J, Lu S, Song X, Jı G, Xıe Y, Wu H
Turk J Med Sci 2022 Aug;52(4):1256-1265. Epub 2022 Aug 10 doi: 10.55730/1300-0144.5431. PMID: 36326420Free PMC Article
Overview of symptoms and treatment for lysinuric protein intolerance.
Noguchi A, Takahashi T
J Hum Genet 2019 Sep;64(9):849-858. Epub 2019 Jun 18 doi: 10.1038/s10038-019-0620-6. PMID: 31213652
Urea cycle disorders in India: clinical course, biochemical and genetic investigations, and prenatal testing.
Bijarnia-Mahay S, Häberle J, Jalan AB, Puri RD, Kohli S, Kudalkar K, Rüfenacht V, Gupta D, Maurya D, Verma J, Shigematsu Y, Yamaguchi S, Saxena R, Verma IC
Orphanet J Rare Dis 2018 Oct 1;13(1):174. doi: 10.1186/s13023-018-0908-1. PMID: 30285816Free PMC Article
Carbohydrate status in patients with phenylketonuria.
Couce ML, Sánchez-Pintos P, Vitoria I, De Castro MJ, Aldámiz-Echevarría L, Correcher P, Fernández-Marmiesse A, Roca I, Hermida A, Martínez-Olmos M, Leis R
Orphanet J Rare Dis 2018 Jun 27;13(1):103. doi: 10.1186/s13023-018-0847-x. PMID: 29945661Free PMC Article
In vivo proton magnetic resonance spectroscopy in phenylketonuria.
Möller HE, Ullrich K, Weglage J
Eur J Pediatr 2000 Oct;159 Suppl 2:S121-5. doi: 10.1007/pl00014374. PMID: 11043158

Recent systematic reviews

Systematic literature review and meta-analysis on the epidemiology of methylmalonic acidemia (MMA) with a focus on MMA caused by methylmalonyl-CoA mutase (mut) deficiency.
Almási T, Guey LT, Lukacs C, Csetneki K, Vokó Z, Zelei T
Orphanet J Rare Dis 2019 Apr 25;14(1):84. doi: 10.1186/s13023-019-1063-z. PMID: 31023387Free PMC Article
Systematic literature review and meta-analysis on the epidemiology of propionic acidemia.
Almási T, Guey LT, Lukacs C, Csetneki K, Vokó Z, Zelei T
Orphanet J Rare Dis 2019 Feb 13;14(1):40. doi: 10.1186/s13023-018-0987-z. PMID: 30760309Free PMC Article
White matter microstructural damage in early treated phenylketonuric patients.
González MJ, Polo MR, Ripollés P, Gassió R, Ormazabal A, Sierra C, Roura RC, Artuch R, Campistol J
Orphanet J Rare Dis 2018 Oct 26;13(1):188. doi: 10.1186/s13023-018-0912-5. PMID: 30367646Free PMC Article
Status of nutrients important in brain function in phenylketonuria: a systematic review and meta-analysis.
Montoya Parra GA, Singh RH, Cetinyurek-Yavuz A, Kuhn M, MacDonald A
Orphanet J Rare Dis 2018 Jun 26;13(1):101. doi: 10.1186/s13023-018-0839-x. PMID: 29941009Free PMC Article
Evaluation of pre-symptomatic nitisinone treatment on long-term outcomes in Tyrosinemia type 1 patients: a systematic review.
Geppert J, Stinton C, Freeman K, Fraser H, Clarke A, Johnson S, Sutcliffe P, Taylor-Phillips S
Orphanet J Rare Dis 2017 Sep 11;12(1):154. doi: 10.1186/s13023-017-0696-z. PMID: 28893311Free PMC Article

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