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Adenosine kinase deficiency(MRT8, FORMERLY)

MedGen UID:
1632232
Concept ID:
C4706555
Disease or Syndrome
Synonyms: Hypermethioninemia due to adenosine kinase deficiency; MENTAL RETARDATION, AUTOSOMAL RECESSIVE 8
SNOMED CT: Hypermethioninemia encephalopathy due to deficiency of adenosine kinase (763721006); Hypermethioninemia encephalopathy due to ADK (adenosine kinase) deficiency (763721006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ADK (10q22.2)
 
Monarch Initiative: MONDO:0100255
OMIM®: 614300
Orphanet: ORPHA289290

Definition

Hypermethioninemia due to adenosine kinase deficiency is an autosomal recessive inborn error of metabolism characterized by global developmental delay, early-onset seizures, mild dysmorphic features, and characteristic biochemical anomalies, including persistent hypermethioninemia with increased levels of S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy); homocysteine is typically normal (summary by Bjursell et al., 2011). [from OMIM]

Clinical features

From HPO
Narrow foot
MedGen UID:
108395
Concept ID:
C0576227
Finding
A foot for which the measured width is below the 5th centile for age; or, a foot that appears disproportionately narrow for its length.
Coarctation of aorta
MedGen UID:
1617
Concept ID:
C0003492
Congenital Abnormality
Coarctation of the aorta is a narrowing or constriction of a segment of the aorta.
Atrial septal defect, ostium secundum type
MedGen UID:
91034
Concept ID:
C0344724
Congenital Abnormality
A kind of atrial septum defect arising from an enlarged foramen ovale, inadequate growth of the septum secundum, or excessive absorption of the septum primum.
Pulmonic stenosis
MedGen UID:
408291
Concept ID:
C1956257
Disease or Syndrome
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Cholestasis
MedGen UID:
925
Concept ID:
C0008370
Disease or Syndrome
Impairment of bile flow due to obstruction in bile ducts.
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Portal fibrosis
MedGen UID:
893107
Concept ID:
C3805083
Disease or Syndrome
Fibroblast proliferation and fiber expansion from the portal areas to the lobule.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Poor speech
MedGen UID:
341172
Concept ID:
C1848207
Finding
Profound global developmental delay
MedGen UID:
766364
Concept ID:
C3553450
Disease or Syndrome
A profound delay in the achievement of motor or mental milestones in the domains of development of a child.
Multifocal epileptiform discharges
MedGen UID:
866864
Concept ID:
C4021219
Finding
An abnormality in cerebral electrical activity recorded along the scalp by electroencephalography (EEG) and being identified at multiple locations (foci).
Increased CSF methionine concentration
MedGen UID:
1687420
Concept ID:
C5139595
Finding
Concentration of methionine in the cerebrospinal fluid above the upper limit of normal.
Prolonged prothrombin time
MedGen UID:
208879
Concept ID:
C0853225
Finding
Increased time to coagulation in the prothrombin time test, which is a measure of the extrinsic pathway of coagulation. The results of the prothrombin time test are often expressed in terms of the International normalized ratio (INR), which is calculated as a ratio of the patient's prothrombin time (PT) to a control PT standardized for the potency of the thromboplastin reagent developed by the World Health Organization (WHO) using the formula
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Hyperbilirubinemia
MedGen UID:
86321
Concept ID:
C0311468
Finding
An increased amount of bilirubin in the blood.
Hypermethioninemia
MedGen UID:
887708
Concept ID:
C4048705
Disease or Syndrome
An increased concentration of methionine in the blood.
Elevated circulating S-adenosyl-L-homocysteine concentration
MedGen UID:
1841887
Concept ID:
C5826621
Finding
Increased concentration of S-adenosyl-L-homocysteine in the blood circulation.
Elevated circulating S-adenosyl-L-methionine concentration
MedGen UID:
1842025
Concept ID:
C5826622
Finding
Concentration S-adenosyl-L-methionine in the blood circulation above the upper limit of normal.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAdenosine kinase deficiency

Professional guidelines

PubMed

Huemer M, Kožich V, Rinaldo P, Baumgartner MR, Merinero B, Pasquini E, Ribes A, Blom HJ
J Inherit Metab Dis 2015 Nov;38(6):1007-19. Epub 2015 Mar 12 doi: 10.1007/s10545-015-9830-z. PMID: 25762406Free PMC Article

Recent clinical studies

Etiology

Becker PH, Demir Z, Mozer Glassberg Y, Sevin C, Habes D, Imbard A, Mussini C, Rozenfeld Bar Lev M, Davit-Spraul A, Benoist JF, Thérond P, Slama A, Jacquemin E, Gonzales E, Gaignard P
Mol Genet Metab 2021 Jan;132(1):38-43. Epub 2020 Nov 28 doi: 10.1016/j.ymgme.2020.11.007. PMID: 33309011
Kožich V, Stabler S
J Nutr 2020 Oct 1;150(Suppl 1):2506S-2517S. doi: 10.1093/jn/nxaa134. PMID: 33000152
Staufner C, Lindner M, Dionisi-Vici C, Freisinger P, Dobbelaere D, Douillard C, Makhseed N, Straub BK, Kahrizi K, Ballhausen D, la Marca G, Kölker S, Haas D, Hoffmann GF, Grünert SC, Blom HJ
J Inherit Metab Dis 2016 Mar;39(2):273-83. Epub 2015 Dec 7 doi: 10.1007/s10545-015-9904-y. PMID: 26642971
Yadav V, Chu CK, Rais RH, Al Safarjalani ON, Guarcello V, Naguib FN, el Kouni MH
J Med Chem 2004 Apr 8;47(8):1987-96. doi: 10.1021/jm030537y. PMID: 15055998
Renouf JA, Wood A, Frazer IH, Thong YH, Chalmers AH
Clin Chem 1989 Jul;35(7):1478-81. PMID: 2547531

Diagnosis

Becker PH, Demir Z, Mozer Glassberg Y, Sevin C, Habes D, Imbard A, Mussini C, Rozenfeld Bar Lev M, Davit-Spraul A, Benoist JF, Thérond P, Slama A, Jacquemin E, Gonzales E, Gaignard P
Mol Genet Metab 2021 Jan;132(1):38-43. Epub 2020 Nov 28 doi: 10.1016/j.ymgme.2020.11.007. PMID: 33309011
Xu J, Yang Q, Zhang X, Liu Z, Cao Y, Wang L, Zhou Y, Zeng X, Ma Q, Xu Y, Wang Y, Huang L, Han Z, Wang T, Stepp D, Bagi Z, Wu C, Hong M, Huo Y
J Endocrinol 2019 Aug;242(2):159-172. doi: 10.1530/JOE-19-0126. PMID: 31189131Free PMC Article
Alhusani A, Obaid A, Blom HJ, Wedell A, Alfadhel M
Neuropediatrics 2019 Feb;50(1):46-50. Epub 2018 Nov 26 doi: 10.1055/s-0038-1676053. PMID: 30477030
Staufner C, Blom HJ, Dionisi-Vici C, Freisinger P, Makhseed N, Ballhausen D, Kölker S, Hoffmann GF, Harting I
Neuroradiology 2016 Jul;58(7):697-703. Epub 2016 Mar 18 doi: 10.1007/s00234-016-1676-z. PMID: 26993811
Huemer M, Kožich V, Rinaldo P, Baumgartner MR, Merinero B, Pasquini E, Ribes A, Blom HJ
J Inherit Metab Dis 2015 Nov;38(6):1007-19. Epub 2015 Mar 12 doi: 10.1007/s10545-015-9830-z. PMID: 25762406Free PMC Article

Therapy

Xu J, Yang Q, Zhang X, Liu Z, Cao Y, Wang L, Zhou Y, Zeng X, Ma Q, Xu Y, Wang Y, Huang L, Han Z, Wang T, Stepp D, Bagi Z, Wu C, Hong M, Huo Y
J Endocrinol 2019 Aug;242(2):159-172. doi: 10.1530/JOE-19-0126. PMID: 31189131Free PMC Article
Huemer M, Kožich V, Rinaldo P, Baumgartner MR, Merinero B, Pasquini E, Ribes A, Blom HJ
J Inherit Metab Dis 2015 Nov;38(6):1007-19. Epub 2015 Mar 12 doi: 10.1007/s10545-015-9830-z. PMID: 25762406Free PMC Article

Prognosis

Becker PH, Demir Z, Mozer Glassberg Y, Sevin C, Habes D, Imbard A, Mussini C, Rozenfeld Bar Lev M, Davit-Spraul A, Benoist JF, Thérond P, Slama A, Jacquemin E, Gonzales E, Gaignard P
Mol Genet Metab 2021 Jan;132(1):38-43. Epub 2020 Nov 28 doi: 10.1016/j.ymgme.2020.11.007. PMID: 33309011

Clinical prediction guides

Renouf JA, Wood A, Frazer IH, Thong YH, Chalmers AH
Clin Chem 1989 Jul;35(7):1478-81. PMID: 2547531
Gruber HE, Koenker R, Luchtman LA, Willis RC, Seegmiller JE
Proc Natl Acad Sci U S A 1985 Oct;82(19):6662-6. doi: 10.1073/pnas.82.19.6662. PMID: 2995977Free PMC Article

Recent systematic reviews

Huemer M, Kožich V, Rinaldo P, Baumgartner MR, Merinero B, Pasquini E, Ribes A, Blom HJ
J Inherit Metab Dis 2015 Nov;38(6):1007-19. Epub 2015 Mar 12 doi: 10.1007/s10545-015-9830-z. PMID: 25762406Free PMC Article

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