Biochemical Genetics

, Volume 56, Issue 1–2, pp 7–21 | Cite as

Aminoacidopathies: Prevalence, Etiology, Screening, and Treatment Options

  • Muhammad Wasim
  • Fazli Rabbi AwanEmail author
  • Haq Nawaz Khan
  • Abdul Tawab
  • Mazhar Iqbal
  • Hina Ayesha


Inborn errors of metabolism (IEMs) are a group of inherited metabolic disorders which are caused by mutations in the specific genes that lead to impaired proteins or enzymes production. Different metabolic pathways are perturbed due to the deficiency or lack of enzymes. To date, more than 500 IEMs have been reported with most of them being untreatable. However, fortunately 91 such disorders are potentially treatable, if diagnosed at an earlier stage of life. IEMs have been classified into different categories and one class of IEMs, characterized by the physiological disturbances of amino acids is called as aminoacidopathies. Out of 91 treatable IEM, thirteen disorders are amino acid related. Aminoacidopathies can be detected by chromatography and mass spectrometry based analytical techniques (e.g., HPLC, GC–MS, LC–MS/MS) for amino acid level changes, and through genetic assays (e.g., PCR, TaqMan Genotyping, DNA sequencing) at the mutation level in the corresponding genes. Hence, this review is focused to describe thirteen common aminoacidopathies namely: Phenylketonuria (PKU), Maple Syrup Urine Disease (MSUD), Homocystinuria/Methylene Tetrahydrofolate Reductase (MTHFR) deficiency, Tyrosinemia type II, Citrullinemia type I and type II, Argininosuccinic aciduria, Carbamoyl Phosphate Synthetase I (CPS) deficiency, Argininemia (arginase deficiency), Hyperornithinemia–Hyperammonemia–Homocitrullinuria (HHH) syndrome, N-Acetylglutamate Synthase (NAGS) deficiency, Ornithine Transcarbamylase (OTC) deficiency, and Pyruvate Dehydrogenase (PDH) complex deficiency. Furthermore, the etiology, prevalence and commonly used analytical techniques for screening of aminoacidopathies are briefly described. This information would be helpful to researchers and clinicians especially from developing countries to initiate newborn screening programs for aminoacidopathies.


Aminoacidopathies Metabolic disorders HPLC LC–MS/MS GC–MS Newborn screening 



This review originated as a result of our research project, “Diagnosis of treatable inborn metabolic disorders of intellectual disability” (Project No. CRP/PAK14-02; Contract No. CRP/14/012) funded by the International Centre for Genetic Engineering and Biotechnology (ICGEB), Italy.

Author Contributions

FRA conceived the idea and revised/approved the manuscript. MW wrote the draft and revised it several times, HNK provided information on genetics of the diseases, AT and MI wrote and revised the analytical/diagnostic section, and HA provided advice on clinical aspects of the described diseases.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Muhammad Wasim
    • 1
  • Fazli Rabbi Awan
    • 1
    Email author
  • Haq Nawaz Khan
    • 1
  • Abdul Tawab
    • 1
  • Mazhar Iqbal
    • 1
  • Hina Ayesha
    • 2
  1. 1.Health Biotechnology DivisionNational Institute for Biotechnology and Genetic Engineering (NIBGE) / [Pakistan Institute of Engineering and Applied Sciences (PIEAS), Islamabad]FaisalabadPakistan
  2. 2.DHQ Hospital, Faisalabad Medical UniversityFaisalabadPakistan

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