Argininosuccinic aciduria

General Information (adopted from Orphanet):

Synonyms, Signs: ASLD
Argininosuccinase deficiency
Argininosuccinic acid lyase deficiency
Argininosuccinate lyase deficiency
ASL deficiency
ASA deficiency
Number of Symptoms 54
OrphanetNr: 23
OMIM Id: 207900
ICD-10: E72.2
UMLs: C0268547
MeSH: D056807
MedDRA: 10058299
Snomed: 41013004

Prevalence, inheritance and age of onset:

Prevalence: <= 9 of 100 000
Inheritance: Autosomal recessive
21312326 [IBIS]
Age of onset: Neonatal
Infancy
Childhood
18647279 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Disorder of urea cycle metabolism and ammonia detoxification
 -Rare genetic disease

Comment:

Argininosuccinic aciduria belongs to the class of urea cycle disorders. It is caused by mutations in the gene ASL encoding the enzyme argininosuccinic acid lyase, one of the six enzymes and two transporters involved in the detoxification of ammonium to urea (PMID:22241104).

Symptom Information: Sort by abundance 

1
 (HPO:0011968) Feeding difficulties Frequent [IBIS] 22241104 IBIS 240 / 7739
2
 (HPO:0008872) Feeding difficulties in infancy 22241104 IBIS 153 / 7739
3
 (HPO:0002013) Vomiting Frequent [IBIS] 21312326 IBIS 191 / 7739
4
 (HPO:0003218) Oroticaciduria Frequent [IBIS] 21312326 IBIS 10 / 7739
5
 (HPO:0001950) Respiratory alkalosis Frequent [IBIS] 21312326 IBIS 7 / 7739
6
 (HPO:0001508) Failure to thrive 6886731 IBIS 454 / 7739
7
 (HPO:0004337) Abnormality of amino acid metabolism Very frequent [Orphanet] 22241104 IBIS 45 / 7739
8
 (HPO:0011966) Elevated plasma citrulline Frequent [IBIS] 21312326 IBIS 5 / 7739
9
 (HPO:0005961) Hypoargininemia Frequent [IBIS] 19592285 IBIS 7 / 7739
10
 (HPO:0003217) Hyperglutaminemia Frequent [IBIS] 21312326 IBIS 9 / 7739
11
 (HPO:0003348) Hyperalaninemia Frequent [IBIS] 21312326 IBIS 19 / 7739
12
 (HPO:0002154) Hyperglycinemia Frequent [IBIS] 21312326 IBIS 12 / 7739
13
 (HPO:0003355) Aminoaciduria Very frequent [IBIS] Very frequent [Orphanet] 22241104 IBIS 65 / 7739
14
 (MedDRA:10058299) Argininosuccinate lyase deficiency Very frequent [IBIS] 21312326 IBIS 1 / 7739
15
 (HPO:0000822) Hypertension 21312326 IBIS 224 / 7739
16
 (HPO:0002900) Hypokalemia 22241104 IBIS 45 / 7739
17
 (HPO:0001987) Hyperammonemia Very frequent [IBIS] Frequent [Orphanet] 23306800 IBIS 50 / 7739
18
 (HPO:0001298) Encephalopathy 19635676 IBIS 72 / 7739
19
 (HPO:0001251) Ataxia Frequent [Orphanet] typical [HPO] 7682674 IBIS 413 / 7739
20
 (HPO:0002066) Gait ataxia Frequent [Orphanet] typical [HPO] 7137886 IBIS 327 / 7739
21
 (HPO:0002311) Incoordination Frequent [Orphanet] 7137886 IBIS 84 / 7739
22
 (HPO:0002312) Clumsiness 7137886 IBIS 28 / 7739
23
 (HPO:0000708) Behavioral abnormality 21312326 IBIS 212 / 7739
24
 (HPO:0007018) Attention deficit hyperactivity disorder 21312326 IBIS 56 / 7739
25
 (HPO:0001328) Specific learning disability Frequent [IBIS] Frequent [Orphanet] 21312326 IBIS 114 / 7739
26
 (HPO:0001289) Confusion 22784324 IBIS 36 / 7739
27
 (HPO:0001263) Global developmental delay Frequent [IBIS] Frequent [Orphanet] 21312326 IBIS 853 / 7739
28
 (HPO:0001249) Intellectual disability Frequent [IBIS] Frequent [Orphanet] 22241104 IBIS 1089 / 7739
29
 (HPO:0001270) Motor delay Frequent [Orphanet] 1594374 IBIS 322 / 7739
30
 (HPO:0001254) Lethargy 21312326 IBIS 104 / 7739
31
 (HPO:0001259) Coma 22241104 IBIS 65 / 7739
32
 (HPO:0000709) Psychosis 2715782 IBIS 61 / 7739
33
 (HPO:0001262) Somnolence 2715782 IBIS 20 / 7739
34
 (HPO:0100543) Cognitive impairment Frequent [IBIS] Frequent [Orphanet] 22901741 IBIS 230 / 7739
35
 (HPO:0002353) EEG abnormality Frequent [Orphanet] 21312326 IBIS 188 / 7739
36
 (HPO:0001250) Seizures Frequent [IBIS] 21312326 IBIS 1245 / 7739
37
 (HPO:0009886) Trichorrhexis nodosa 21312326 IBIS 12 / 7739
38
 (HPO:0011362) Abnormal hair quantity Occasional [Orphanet] 4165309 IBIS 92 / 7739
39
 (HPO:0002299) Brittle hair 4165309 IBIS 52 / 7739
40
 (HPO:0004779) Brittle scalp hair 21312326 IBIS 4 / 7739
41
 (HPO:0002208) Coarse hair Frequent [IBIS] 22241104 IBIS 58 / 7739
42
 (HPO:0001808) Fragile nails 4165309 IBIS 21 / 7739
43
 (HPO:0001596) Alopecia 4165309 IBIS 162 / 7739
44
 (HPO:0001006) Hypotrichosis Occasional [Orphanet] 4165309 IBIS 219 / 7739
45
 (HPO:0002209) Sparse scalp hair Occasional [Orphanet] 22241104 IBIS 59 / 7739
46
 (HPO:0002045) Hypothermia Frequent [IBIS] 21312326 IBIS 27 / 7739
47
 (HPO:0001394) Cirrhosis 21312326 IBIS 102 / 7739
48
 (HPO:0001395) Hepatic fibrosis 21312326 IBIS 67 / 7739
49
 (HPO:0012115) Hepatitis 21312326 IBIS 24 / 7739
50
 (HPO:0002240) Hepatomegaly 21312326 IBIS 467 / 7739
51
 (HPO:0002789) Tachypnea 21312326 IBIS 48 / 7739
52
 (HPO:0001510) Growth delay 6886731 IBIS 295 / 7739
53
 (OMIM) Argininosuccinicaciduria Frequent [IBIS] 21312326 IBIS 1 / 7739
54
 (OMIM) Hepatic argininosuccinase deficiency 21312326 IBIS 1 / 7739

Associated genes:

ASL;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Argininosuccinic aciduria is an autosomal recessive disorder of the urea cycle. Urea cycle disorders are characterized by the triad of hyperammonemia, encephalopathy, and respiratory alkalosis. Five disorders involving different defects in the biosynthesis of the enzymes of the ...
Diagnosis OMIM - Prenatal Diagnosis

Pijpers et al. (1990) established the diagnosis of argininosuccinic aciduria in both fetuses of a dizygotic pregnancy, using transabdominal chorionic villus sampling at 10 weeks' gestation. Kleijer et al. (2002) performed successful molecular ...
Clinical Description OMIM Two forms of argininosuccinic aciduria have been recognized: an early-onset, or malignant, type and a late-onset type.

As originally described by Allan et al. (1958), onset of symptoms of argininosuccinic aciduria occurs in the first weeks ...
Molecular genetics OMIM - Early Identification of Complementation Groups

In study of 5 cell lines from patients with argininosuccinate lyase deficiency, Cathelineau et al. (1981) observed 2 complementation groups. Since the restoration of activity was not total, the complementation ...
Population genetics OMIM The prevalence of argininosuccinic aciduria is estimated to be 1 in 150,000 (Testai and Gorelick, 2010).