Hypermethioninemia encephalopathy due to adenosine kinase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: ADK hypermethioninemia
Hypermethioninemia encephalopathy due to ADK deficiency
Number of Symptoms 92
OrphanetNr: 289290
OMIM Id: 614300
ICD-10: E72.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
21963049 [IBIS]
Age of onset: Neonatal
21963049 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
Disorder of methionine cycle and sulfur amino acid metabolism
 -Rare genetic disease
 -Rare neurologic disease
Neurometabolic disease
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000011) Neurogenic bladder 27500280 IBIS 11 / 7739
2
 (HPO:0000016) Urinary retention 27500280 IBIS 7 / 7739
3
 (HPO:0004386) Gastrointestinal inflammation 27500280 IBIS 5 / 7739
4
 (MedDRA:10049733) Blood homocysteine increased 27500280 IBIS 1 / 7739
5
 (HPO:0003235) Hypermethioninemia 21963049; 26642971; 27500280 IBIS 8 / 7739
6
 (HPO:0000670) Carious teeth 27500280 IBIS 145 / 7739
7
 (HPO:0002209) Sparse scalp hair 26642971; 27500280 IBIS 59 / 7739
8
 (HPO:0010668) Abnormality of the zygomatic bone 27500280 IBIS 1 / 7739
9
 (HPO:0005280) Depressed nasal bridge 27500280 IBIS 381 / 7739
10
 (HPO:0000494) Downslanted palpebral fissures 26642971; 27500280 IBIS 328 / 7739
11
 (HPO:0000316) Hypertelorism 21963049; 26642971; 27500280 IBIS 644 / 7739
12
 (HPO:0002007) Frontal bossing 21963049; 26642971; 27500280 IBIS 366 / 7739
13
 (HPO:0001999) Abnormal facial shape 21963049; 27500280 IBIS 169 / 7739
14
 (MedDRA:10030963) Oral candidiasis 27500280 IBIS 4 / 7739
15
 (HPO:0000988) Skin rash 27500280 IBIS 98 / 7739
16
 (HPO:0001051) Seborrheic dermatitis 27500280 IBIS 25 / 7739
17
 (HPO:0005518) Erythrocyte macrocytosis 27500280 IBIS 13 / 7739
18
 (HPO:0002910) Elevated hepatic transaminases 26642971; 27500280 IBIS 158 / 7739
19
 (HPO:0002240) Hepatomegaly 26642971; 27500280 IBIS 467 / 7739
20
 (HPO:0030148) Heart murmur 27500280 IBIS 29 / 7739
21
 (HPO:0001252) Muscular hypotonia 21963049; 27500280 IBIS 990 / 7739
22
 (HPO:0002421) Poor head control 27500280 IBIS 23 / 7739
23
 (HPO:0001263) Global developmental delay 26642971; 27500280 IBIS 853 / 7739
24
 (HPO:0011968) Feeding difficulties 26642971; 27500280 IBIS 240 / 7739
25
 (HPO:0000737) Irritability 27500280 IBIS 93 / 7739
26
 (HPO:0001945) Fever 27500280 IBIS 218 / 7739
27
 (HPO:0001629) Ventricular septal defect 27500280 IBIS 316 / 7739
28
 (HPO:0001643) Patent ductus arteriosus 26642971; 27500280 IBIS 228 / 7739
29
 (HPO:0011951) Aspiration pneumonia 27500280 IBIS 6 / 7739
30
 (HPO:0002098) Respiratory distress 27500280 IBIS 75 / 7739
31
 (HPO:0000952) Jaundice 27500280 IBIS 105 / 7739
32
 (HPO:0001889) Megaloblastic anemia 26642971 IBIS 28 / 7739
33
 (HPO:0006579) Prolonged neonatal jaundice 26642971 IBIS 25 / 7739
34
 (HPO:0001251) Ataxia 26642971 IBIS 413 / 7739
35
 (HPO:0002013) Vomiting 26642971 IBIS 191 / 7739
36
 (HPO:0006254) Elevated alpha-fetoprotein 26642971 IBIS 10 / 7739
37
 (HPO:0003256) Abnormality of the coagulation cascade 26642971 IBIS 19 / 7739
38
 (HPO:0001508) Failure to thrive 21963049; 26642971 IBIS 454 / 7739
39
 (HPO:0000256) Macrocephaly 21963049; 26642971 IBIS 298 / 7739
40
 (HPO:0011096) Peripheral demyelination 26642971 IBIS 28 / 7739
41
 (HPO:0000369) Low-set ears 26642971 IBIS 372 / 7739
42
 (HPO:0000445) Wide nose 26642971 IBIS 190 / 7739
43
 (HPO:0001081) Cholelithiasis 26642971 IBIS 36 / 7739
44
 (HPO:0001786) Narrow foot 21963049; 26642971 IBIS 11 / 7739
45
 (HPO:0004283) Narrow palm 21963049; 26642971 IBIS 8 / 7739
46
 (HPO:0000164) Abnormality of the teeth 26642971 IBIS 291 / 7739
47
 (HPO:0012736) Profound global developmental delay 26642971 IBIS 3 / 7739
48
 (HPO:0001541) Ascites 26642971 IBIS 94 / 7739
49
 (HPO:0001942) Metabolic acidosis 26642971 IBIS 81 / 7739
50
 (HPO:0006571) Reduced number of intrahepatic bile ducts 26642971 IBIS 4 / 7739
51
 (HPO:0012115) Hepatitis 26642971 IBIS 24 / 7739
52
 (HPO:0000735) Impaired social interactions 26642971 IBIS 20 / 7739
53
 (HPO:0000556) Retinal dystrophy 26642971 IBIS 65 / 7739
54
 (HPO:0002465) Poor speech 26642971 IBIS 31 / 7739
55
 (HPO:0001396) Cholestasis 26642971 IBIS 136 / 7739
56
 (HPO:0001631) Atria septal defect rare [HPO:skoehler] 21963049; 26642971 IBIS 274 / 7739
57
 (HPO:0006566) Neonatal cholestatic liver disease 26642971 IBIS 2 / 7739
58
 (HPO:0001662) Bradycardia 26642971 IBIS 41 / 7739
59
 (HPO:0001522) Death in infancy 26642971 IBIS 275 / 7739
60
 (HPO:0006580) Portal fibrosis 21963049; 26642971 IBIS 10 / 7739
61
 (HPO:0001250) Seizures 21963049; 26642971 IBIS 1245 / 7739
62
 (HPO:0011344) Severe global developmental delay 21963049; 26642971 IBIS 46 / 7739
63
 (HPO:0008947) Infantile muscular hypotonia 21963049; 26642971 IBIS 482 / 7739
64
 (HPO:0001655) Patent foramen ovale 26642971 IBIS 31 / 7739
65
 (HPO:0011682) Perimembranous ventricular septal defect 26642971 IBIS 6 / 7739
66
 (HPO:0001987) Hyperammonemia 26642971 IBIS 50 / 7739
67
 (HPO:0001410) Decreased liver function 21963049; 26642971 IBIS 59 / 7739
68
 (HPO:0002904) Hyperbilirubinemia 26642971 IBIS 32 / 7739
69
 (HPO:0000842) Hyperinsulinemia 26642971 IBIS 39 / 7739
70
 (HPO:0002045) Hypothermia 26642971 IBIS 27 / 7739
71
 (HPO:0000961) Cyanosis 26642971 IBIS 60 / 7739
72
 (HPO:0001988) Recurrent hypoglycemia 26642971 IBIS 6 / 7739
73
 (HPO:0000407) Sensorineural hearing impairment rare [HPO:skoehler] 21963049 IBIS 524 / 7739
74
 (HPO:0001680) Coarctation of aorta rare [HPO:skoehler] 21963049 IBIS 57 / 7739
75
 (HPO:0001684) Secundum atrial septal defect 21963049 IBIS 14 / 7739
76
 (HPO:0001642) Pulmonic stenosis rare [HPO:skoehler] 21963049 IBIS 89 / 7739
77
 (HPO:0002415) Leukodystrophy 21963049 IBIS 30 / 7739
78
 (HPO:0002059) Cerebral atrophy 21963049 IBIS 171 / 7739
79
 (HPO:0001397) Hepatic steatosis 21963049 IBIS 75 / 7739
80
 (HPO:0003819) Death in childhood 21963049 IBIS 42 / 7739
81
 (HPO:0003323) Progressive muscle weakness 21963049 IBIS 17 / 7739
82
 (HPO:0000750) Delayed speech and language development 21963049 IBIS 197 / 7739
83
 (HPO:0002908) Conjugated hyperbilirubinemia 21963049 IBIS 21 / 7739
84
 (HPO:0008625) Severe sensorineural hearing impairment 150 / 7739
85
 (HPO:0008527) Congenital sensorineural hearing impairment 165 / 7739
86
 (HPO:0004415) Pulmonary artery stenosis 25 / 7739
87
 (HPO:0004971) Pulmonary artery hypoplasia 15 / 7739
88
 (HPO:0005113) Dilatation of the aortic arch 12 / 7739
89
 (HPO:0001671) Abnormality of the cardiac septa 55 / 7739
90
 (HPO:0001324) Muscle weakness 859 / 7739
91
 (HPO:0003202) Skeletal muscle atrophy 281 / 7739
92
 (HPO:0010547) Muscle flaccidity 466 / 7739

Associated genes:

ADK;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Clinical Description OMIM Bjursell et al. (2011) reported 2 Swedish sibs with severe developmental delay, mild liver dysfunction, and hypermethioninemia. Both had failure to thrive in the neonatal period and later showed hypotonia, profound psychomotor delay, and liver dysfunction. Both developed seizures ...
Molecular genetics OMIM By exome sequencing, Bjursell et al. (2011) identified a homozygous mutation in the ADK gene (102750.0001) in 2 Swedish sibs with severe developmental delay, mild liver dysfunction, and persistent hypermethioninemia. Subsequent analysis of this gene in Malaysian patients with ...