Adenosine Kinase Deficiency: Report and Review

Abstract

Adenosine kinase (ADK) deficiency (OMIM [online mendelian inheritance in man]: 614300) is an autosomal recessive disorder of adenosine and methionine metabolism, with a unique clinical phenotype, mainly involving the central nervous system and dysmorphic features. Patients usually present early in life with sepsis-like symptoms, respiratory difficulties, and neonatal jaundice. Subsequently, patients demonstrate hypotonia and global developmental delay. Biochemically, methionine is elevated with normal homocysteine levels and the diagnosis is confirmed through molecular analysis of the ADK gene. There is no curative treatment; however, a methionine-restricted diet has been tried with variable outcomes. Herein, we report a 4-year-old Saudi female with global developmental delay, hypotonia, and dysmorphic features. Interestingly, she has a tall stature, developmental dysplasia of the hip, optic nerve gliosis, and tigroid fundus. We found a mutation not reported previously and we compared the current case with previously reported cases. We alert clinicians to consider ADK deficiency in any neonate presenting with global developmental delay, hypotonia, dysmorphic features, and high methionine levels.

Keywords

methionine - ADK - adenosine kinase deficiency - adenosine - inborn errors of methionine

Ethics Approval and Consent to Participate

This study was approved by the institutional review board office at King Abdullah International Medical Research Centre (KIMARC; study number: RC16/113/R).

Conflict of Interests

None.

Author Contributions

A.A.: wrote the first draft and edited the subsequent version of the manuscript.

A.O.: collected the clinical data and edited the manuscript.

A.W.: edited the manuscript and reviewed the clinical data.

H.J.B.: edited the manuscript and reviewed the clinical data.

M.A.: supervised the work associated with preparing, writing, and submitting the manuscript and contributed to the clinical diagnosis and management of the patient.

All authors have read and approve the final draft of the manuscript.

• References

• 1 Bjursell MK, Blom HJ, Cayuela JA. , et al. Adenosine kinase deficiency disrupts the methionine cycle and causes hypermethioninemia, encephalopathy, and abnormal liver function. Am J Hum Genet 2011; 89 (04) 507-515
• 2 Staufner C, Lindner M, Dionisi-Vici C. , et al. Adenosine kinase deficiency: expanding the clinical spectrum and evaluating therapeutic options. J Inherit Metab Dis 2016; 39 (02) 273-283
• 3 Spychala J, Datta NS, Takabayashi K. , et al. Cloning of human adenosine kinase cDNA: sequence similarity to microbial ribokinases and fructokinases. Proc Natl Acad Sci U S A 1996; 93 (03) 1232-1237
• 4 Boison D. Adenosine kinase: exploitation for therapeutic gain. Pharmacol Rev 2013; 65 (03) 906-943
• 5 Barić I. Inherited disorders in the conversion of methionine to homocysteine. J Inherit Metab Dis 2009; 32 (04) 459-471
• 6 Baric I, Fumic K, Glenn B. , et al. S-adenosylhomocysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolism. Proc Natl Acad Sci U S A 2004; 101 (12) 4234-4239
• 7 Boison D, Scheurer L, Zumsteg V. , et al. Neonatal hepatic steatosis by disruption of the adenosine kinase gene. Proc Natl Acad Sci U S A 2002; 99 (10) 6985-6990
• 8 Shakiba M, Mahjoub F, Fazilaty H. , et al. Adenosine kinase deficiency with neurodevelopemental delay and recurrent hepatic dysfunction: A case report. Adv Rare Dis 2016; 3: 3
• 9 Mudd SH. Hypermethioninemias of genetic and non-genetic origin: A review. Am J Med Genet C Semin Med Genet 2011; 157C (01) 3-32