Adenosine kinase deficiency with neurodevelopemental delay and recurrent hepatic dysfunction: A case report

Shakiba, Marjan; Mahjoub, Fatemeh; Fazilaty, Hassan; Rezagholizadeh, Fereshteh; Shakiba, Arghavan; Ziadlou, Maryam; Gahl, William A.; Behnam, Babak

doi:10.12715/ard.2014.3.2

Cited by 10 publications

(6 citation statements)

References 10 publications

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“…Psychomotor delay and muscle hypotonia were commonly reported among ADK-deficient patients and were observed in our patient (2)(3)(4)(5)(6)(7). Ten-year post-LTx follow-up revealed a progressive neurological disease as a global developmental delay, ataxia, and spasticity development.…”

Section: Neurologic Phenotype In Adk Deficiencysupporting

confidence: 59%

“…Regarding other biochemical markers of ADK deficiency, plasma SAH and SAM concentrations are the most reliable markers (2)(3)(4)(5)(6)(7). In all the reported ADK-deficient patients, SAM was elevated while SAH was elevated in all beyond one patient described by Bjursell et al (3).…”

Section: Biochemical and Molecular Phenotype Of Adk Deficiencymentioning

confidence: 93%

“…ADK deficiency was first clinically described by Bjursell et al in 2011 (3). So far, a total number of 27 patients with ADK deficiency have been reported (2)(3)(4)(5)(6)(7). ADK-deficient patients presented with liver dysfunction (most commonly with prolonged neonatal cholestatic jaundice), delayed psychomotor development, and neurological features including generalized hypotonia and epilepsy (2)(3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…So far, a total number of 27 patients with ADK deficiency have been reported (2)(3)(4)(5)(6)(7). ADK-deficient patients presented with liver dysfunction (most commonly with prolonged neonatal cholestatic jaundice), delayed psychomotor development, and neurological features including generalized hypotonia and epilepsy (2)(3)(4)(5)(6)(7). The final diagnosis was usually confirmed by genetic studies, including ADK gene sequencing or whole exome sequencing (WES).…”

Section: Introductionmentioning

confidence: 99%

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Case Report: Adenosine kinase deficiency diagnosed 10 years after liver transplantation: Novel phenotypic insights

Lipiński

Ciara²,

Jurkiewicz³

et al. 2022

Front. Pediatr.

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Adenosine kinase (ADK) deficiency is a rare inborn error of methionine and adenosine metabolism. So far, a total of 27 patients with ADK deficiency have been reported. Here, we describe the first Polish patient diagnosed with ADK deficiency, aiming to highlight the clinical presentation of disease, emphasize diagnostic difficulties, and report the long-term follow-up. Six-month-old patient presented with cholestatic liver disease, macrocytic anemia, developmental delay, generalized hypotonia, delayed brain myelination, and elevated levels of serum methionine. A decrease of mitochondrial respiratory chain complex II and III activity were found in the postnuclear supernatants obtained from skeletal muscle biopsy. The patient underwent living-donor liver transplantation (LTx) at 14 months of age. Ten-year follow-up after LTx revealed a preserved good liver function, persistent regenerative macrocytic anemia, progressive neurological disease but disappearance of brain MR changes, short stature, and cortisol deficiency. Whole exome sequencing revealed the patient to be affected with two novel ADK variants, which pathogenicity was confirmed biochemically by demonstration of elevated concentration of S-adenosylhomocysteine.

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Section: Neurologic Phenotype In Adk Deficiencysupporting

confidence: 59%

Section: Biochemical and Molecular Phenotype Of Adk Deficiencymentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Case Report: Adenosine kinase deficiency diagnosed 10 years after liver transplantation: Novel phenotypic insights

Lipiński

Ciara²,

Jurkiewicz³

et al. 2022

Front. Pediatr.

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show abstract

“…ADK deficiency is a very rare inborn error of metabolism, and is characterized by defects in transmethylation reactions associated with developmental delay, hepatic encephalopaties as well as seizures in some individuals (Bjursell et al, 2011;Shakiba et al, 2016;Staufner et al, 2016;Alhusani et al, 2019;Becker et al, 2021). Mutations of ADK or modification of ADK levels have been associated with several diseases (Garcia-Gil et al, 2018), such as stroke (Shen et al, 2011), Rasmussen encephalitis (Luan et al, 2013), focal cortical dysplasia (Luan et al, 2015), epilepsy (Boison, 2016) and gliomas (de Groot et al, 2012;Huang et al, 2015), as well as in cognition deficits (Bjursell et al, 2011;Singer et al, 2012;Sandau et al, 2016;Shakiba et al, 2016;Staufner et al, 2016;Osborne et al, 2018;Kuptanon et al, 2019). Notably, genetic variants of ADK are associated with posttraumatic epilepsy in humans (Diamond et al, 2015).…”

Section: Adenosine Kinasementioning

confidence: 99%

Metabolic Aspects of Adenosine Functions in the Brain

et al. 2021

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Adenosine, acting both through G-protein coupled adenosine receptors and intracellularly, plays a complex role in multiple physiological and pathophysiological processes by modulating neuronal plasticity, astrocytic activity, learning and memory, motor function, feeding, control of sleep and aging. Adenosine is involved in stroke, epilepsy and neurodegenerative pathologies. Extracellular concentration of adenosine in the brain is tightly regulated. Adenosine may be generated intracellularly in the central nervous system from degradation of AMP or from the hydrolysis of S-adenosyl homocysteine, and then exit via bi-directional nucleoside transporters, or extracellularly by the metabolism of released nucleotides. Inactivation of extracellular adenosine occurs by transport into neurons or neighboring cells, followed by either phosphorylation to AMP by adenosine kinase or deamination to inosine by adenosine deaminase. Modulation of the nucleoside transporters or of the enzymatic activities involved in the metabolism of adenosine, by affecting the levels of this nucleoside and the activity of adenosine receptors, could have a role in the onset or the development of central nervous system disorders, and can also be target of drugs for their treatment. In this review, we focus on the contribution of 5′-nucleotidases, adenosine kinase, adenosine deaminase, AMP deaminase, AMP-activated protein kinase and nucleoside transporters in epilepsy, cognition, and neurodegenerative diseases with a particular attention on amyotrophic lateral sclerosis and Huntington’s disease. We include several examples of the involvement of components of the adenosine metabolism in learning and of the possible use of modulators of enzymes involved in adenosine metabolism or nucleoside transporters in the amelioration of cognition deficits.

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Clinical utility of methionine restriction in adenosine kinase deficiency

et al. 2021

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Adenosine kinase (ADK) deficiency is a rare autosomal recessive inborn error of metabolism involving the methionine and purine metabolic pathways. Prior reports show that most patients present in infancy with jaundice, hypotonia, developmental delay, and mild dysmorphic features. Characteristic biochemical findings included hypoglycemic hyperinsulinism, cholestasis, elevated liver functions, methionine, S‐adenosylhomocysteine, and S‐adenosylmethionine, with normal or mildly elevated homocysteine level. Brain imaging demonstrated atrophy, hydrocephalus, and delayed myelination. There are 26 reported patients of ADK deficiency, of which 14 patients were placed on a methionine‐restricted diet. Clinical improvement with methionine restriction was not well described. Case report We report an infant who presented at birth with persistently elevated ammonia (100‐163 μmol/L), hypoglycemia, cholestasis, and liver dysfunction. The initial metabolic and genetic work‐up was nondiagnostic, with only a mildly increased plasma methionine level (51 [<38 μmol/L]). Iron depositions in the liver and in lip mucosa led to suspicion of gestational alloimmune liver disease. Immunoglobulin therapy and exchange transfusion treatments demonstrated transient clinical and biochemical improvements. However, subsequent episodes of acute liver failure with development of neurological abnormalities led to further evaluation. Metabolic studies showed a 25‐fold increase in plasma methionine level at 8 months of life (1022 [<38 μmol/L]) with white matter abnormalities on brain MRI. Expanded molecular testing identified the disease. Urinary purines profile showed elevations of adenosine and related metabolites. Introduction of a low‐methionine diet resulted in rapid clinical amelioration, improvement of brain MRI findings, and normalization of liver functions and methionine levels.

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Adenosine kinase deficiency with neurodevelopemental delay and recurrent hepatic dysfunction: A case report

Cited by 10 publications

References 10 publications

Case Report: Adenosine kinase deficiency diagnosed 10 years after liver transplantation: Novel phenotypic insights

Case Report: Adenosine kinase deficiency diagnosed 10 years after liver transplantation: Novel phenotypic insights

Metabolic Aspects of Adenosine Functions in the Brain

Clinical utility of methionine restriction in adenosine kinase deficiency

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