Adenylosuccinate lyase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: ADSL deficiency
Adenylosuccinase deficiency
Number of Symptoms 86
OrphanetNr: 46
OMIM Id: 103050
ICD-10: E79.8
UMLs: C0268126
MeSH: C538235
MedDRA:
Snomed: 15285008

Prevalence, inheritance and age of onset:

Prevalence: > 80 cases - PMID: 25112391 [IBIS]
Inheritance: Autosomal recessive
- PMID: 27504266 [IBIS]
Age of onset: Neonatal
Infancy
Childhood
- PMID: 27504266 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: AARSKOG SYNDROME, AUTOSOMAL DOMINANT
 -AARSKOG SYNDROME, AUTOSOMAL DOMINANT
Disorder of purine metabolism
 -Rare genetic disease
Rare disease with autism
 -Rare genetic disease
 -Rare neurologic disease
Syndromic neurometabolic disease with non-X-linked intellectual deficit
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Three different forms have been recognized defined by the age of onset and the progression of symptoms: the fatal neonatal form, the severe form or type I presenting within the first months of life characterized by a severe clinical course, and type II, which is the mild/moderate form presenting within the first years of life with hypotonia and developmental delay. Approximately 80 individuals have been reported in the literature, with 5-10% of cases being the fatal neonatal form, 70-80% of cases being the severe form or type I and 15-20% of type II form (PMID:27504266).

Symptom Information: Sort by abundance 

1
 (HPO:0008872) Feeding difficulties in infancy 25112391; 23622405 IBIS 153 / 7739
2
 (HPO:0002013) Vomiting 25112391 IBIS 191 / 7739
3
 (HPO:0000483) Astigmatism 27504266 IBIS 67 / 7739
4
 (HPO:0000657) Oculomotor apraxia 27504266 IBIS 54 / 7739
5
 (HPO:0000486) Strabismus 27504266; 25112391 IBIS 576 / 7739
6
 (HPO:0000505) Visual impairment 27504266 IBIS 297 / 7739
7
 (HPO:0100704) Cortical visual impairment 25112391 IBIS 28 / 7739
8
 (HPO:0002089) Pulmonary hypoplasia 25112391 IBIS 80 / 7739
9
 (HPO:0002181) Cerebral edema 25112391 IBIS 19 / 7739
10
 (HPO:0003202) Skeletal muscle atrophy 23622405 IBIS 281 / 7739
11
 (HPO:0003808) Abnormal muscle tone 25112391 IBIS 3 / 7739
12
 (HPO:0001252) Muscular hypotonia 25112391 IBIS 990 / 7739
13
 (HPO:0001290) Generalized hypotonia 25112391; 23622405 IBIS 51 / 7739
14
 (HPO:0008936) Muscular hypotonia of the trunk 25112391 IBIS 77 / 7739
15
 (HPO:0001336) Myoclonus 25112391 IBIS 115 / 7739
16
 (HPO:0001298) Encephalopathy 25112391 IBIS 72 / 7739
17
 (HPO:0007256) Abnormal pyramidal signs 25112391 IBIS 116 / 7739
18
 (HPO:0001276) Hypertonia 27504266 IBIS 317 / 7739
19
 (HPO:0001257) Spasticity 25112391 IBIS 251 / 7739
20
 (HPO:0001251) Ataxia 25112391 IBIS 413 / 7739
21
 (HPO:0002066) Gait ataxia 25112391 IBIS 327 / 7739
22
 (HPO:0002071) Abnormality of extrapyramidal motor function 25112391 IBIS 76 / 7739
23
 (HPO:0100710) Impulsivity 25112391 IBIS 16 / 7739
24
 (HPO:0000817) Poor eye contact 25112391; 23622405 IBIS 26 / 7739
25
 (HPO:0000729) Autistic behavior 27504266; 25112391; 23622405 IBIS 27 / 7739
26
 (HPO:0100024) Conspicuously happy disposition 25112391 IBIS 5 / 7739
27
 (HPO:0000748) Inappropriate laughter 25112391 IBIS 5 / 7739
28
 (HPO:0000713) Agitation 25112391; 23622405 IBIS 18 / 7739
29
 (HPO:0000718) Aggressive behavior 25112391 IBIS 109 / 7739
30
 (HPO:0007281) Developmental stagnation 25112391 IBIS 6 / 7739
31
 (HPO:0011343) Moderate global developmental delay 25112391 IBIS 5 / 7739
32
 (HPO:0011344) Severe global developmental delay 25112391 IBIS 46 / 7739
33
 (HPO:0001249) Intellectual disability 27504266; 25112391 IBIS 1089 / 7739
34
 (HPO:0001270) Motor delay 23622405 IBIS 322 / 7739
35
 (HPO:0000737) Irritability 25112391 IBIS 93 / 7739
36
 (HPO:0001254) Lethargy 25112391 IBIS 104 / 7739
37
 (HPO:0001259) Coma 25112391 IBIS 65 / 7739
38
 (HPO:0002329) Drowsiness 25112391 IBIS 19 / 7739
39
 (HPO:0100716) Self-injurious behavior 25112391; 23622405 IBIS 43 / 7739
40
 (HPO:0000736) Short attention span 25112391 IBIS 16 / 7739
41
 (HPO:0000733) Stereotypy 25112391; 23622405 IBIS 58 / 7739
42
 (HPO:0012172) Stereotypical body rocking 25112391 IBIS 1 / 7739
43
 (HPO:0000750) Delayed speech and language development 25112391 IBIS 197 / 7739
44
 (HPO:0002167) Neurological speech impairment 25112391 IBIS 308 / 7739
45
 (HPO:0002375) Hypokinesia 25112391 IBIS 25 / 7739
46
 (HPO:0000752) Hyperactivity 25112391 IBIS 140 / 7739
47
 (HPO:0001250) Seizures 27504266; 25112391; 23622405 IBIS 1245 / 7739
48
 (HPO:0011097) Epileptic spasms 25112391 IBIS 45 / 7739
49
 (HPO:0012469) Infantile spasms 25112391 IBIS 18 / 7739
50
 (HPO:0002133) Status epilepticus 25112391 IBIS 59 / 7739
51
 (HPO:0011152) Early onset absence seizures 25112391 IBIS 1 / 7739
52
 (HPO:0001558) Decreased fetal movement 23622405 IBIS 74 / 7739
53
 (HPO:0001511) Intrauterine growth retardation 25112391; 23622405 IBIS 358 / 7739
54
 (HPO:0002804) Arthrogryposis multiplex congenita 25112391 IBIS 93 / 7739
55
 (HPO:0000303) Mandibular prognathia 25112391 IBIS 179 / 7739
56
 (HPO:0005469) Flat occiput 25112391 IBIS 30 / 7739
57
 (HPO:0000248) Brachycephaly 25112391; 23622405 IBIS 222 / 7739
58
 (HPO:0000256) Macrocephaly 27504266 IBIS 298 / 7739
59
 (HPO:0000252) Microcephaly Rare [HPO:probinson] 27504266; 25112391; 23622405 IBIS 832 / 7739
60
 (HPO:0000341) Narrow forehead 27504266 IBIS 96 / 7739
61
 (HPO:0011220) Prominent forehead 27504266 IBIS 137 / 7739
62
 (HPO:0005487) Prominent metopic ridge 25112391 IBIS 28 / 7739
63
 (HPO:0100247) Recurrent singultus 25112391 IBIS 7 / 7739
64
 (HPO:0000273) Facial grimacing 25112391 IBIS 6 / 7739
65
 (HPO:0001999) Abnormal facial shape 25112391 IBIS 169 / 7739
66
 (HPO:0000687) Widely spaced teeth 25112391 IBIS 40 / 7739
67
 (HPO:0000343) Long philtrum 25112391; 23622405 IBIS 262 / 7739
68
 (HPO:0000319) Smooth philtrum 25112391 IBIS 72 / 7739
69
 (HPO:0000219) Thin upper lip vermilion 25112391; 23622405 IBIS 112 / 7739
70
 (HPO:0000154) Wide mouth 25112391 IBIS 137 / 7739
71
 (HPO:0000463) Anteverted nares 25112391 IBIS 305 / 7739
72
 (HPO:0003196) Short nose 25112391 IBIS 264 / 7739
73
 (HPO:0000369) Low-set ears 25112391 IBIS 372 / 7739
74
 (HPO:0005949) Apneic episodes in infancy 25112391 IBIS 5 / 7739
75
 (HPO:0001510) Growth delay 23622405 IBIS 295 / 7739
76
 (HPO:0011400) Abnormal CNS myelination 25112391 IBIS 10 / 7739
77
 (HPO:0002500) Abnormality of the cerebral white matter 25112391 IBIS 73 / 7739
78
 (HPO:0006855) Cerebellar vermis atrophy 25112391 IBIS 8 / 7739
79
 (HPO:0002120) Cerebral cortical atrophy 25112391 IBIS 187 / 7739
80
 (HPO:0007371) Corpus callosum atrophy 25112391 IBIS 14 / 7739
81
 (HPO:0001522) Death in infancy 25112391 IBIS 275 / 7739
82
 (HPO:0012448) Delayed myelination 25112391 IBIS 51 / 7739
83
 (HPO:0001339) Lissencephaly 25112391 IBIS 30 / 7739
84
 (HPO:0002878) Respiratory failure 27504266; 25112391 IBIS 57 / 7739
85
 (MedDRA:10051004) Floppy infant 25112391 IBIS 5 / 7739
86
 (MedDRA:10051139) Foetal heart rate abnormal 23622405 IBIS 2 / 7739

Associated genes:

ADSL;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Diagnosis OMIM Maddocks and Reed (1989) described a sensitive and specific test for succinyladenosine in the urine.

Jaeken et al. (1992) suggested that a modified Bratton-Marshall test, originally designed as an assay for sulfonamides, would be a practical screening ...
Clinical Description OMIM In 3 children with severe psychomotor delay and autism, Jaeken and Van den Berghe (1984) found succinyladenosine and succinylaminoimidazole carboxamide (SAICA) ribotide in the body fluids. Concentrations of both compounds were about 100 micromol/l in CSF, between 5 and ...
Molecular genetics OMIM In 2 affected Moroccan sibs reported by Jaeken and Van den Berghe (1984), Stone et al. (1992) identified a point mutation in the ADSL gene (608222.0001).

Marie et al. (1999) found reports of 9 missense mutations in ...