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AICA-ribosiduria

MedGen UID:
332474
Concept ID:
C1837530
Disease or Syndrome
Synonyms: AICA-ribosiduria due to ATIC deficiency; AICAR transformylase/IMP cyclohydrolase deficiency; ATIC DEFICIENCY
SNOMED CT: 5-amino-4-imidazole carboxamide ribosiduria (725289009); ATIC (5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/imp cyclohydrolase) deficiency (725289009); AICA (5-amino-4-imidazole carboxamide) ribosiduria (725289009)
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): ATIC (2q35)
 
Monarch Initiative: MONDO:0012099
OMIM®: 608688
Orphanet: ORPHA250977

Definition

AICA-ribosiduria is characterized by severe to profound global neurodevelopmental impairment, severe visual impairment due to chorioretinal atrophy, ante-postnatal growth impairment, and severe scoliosis. Dysmorphic features include coarse facies and upturned nose. Early-onset epilepsy may occur. Less common features may include aortic coarctation, chronic hepatic cytolysis, minor genital malformations, and nephrocalcinosis (Ramond et al., 2020). [from OMIM]

Clinical features

From HPO
Clitoral hypertrophy
MedGen UID:
57848
Concept ID:
C0156394
Finding
Hypertrophy of the clitoris.
Fused labia minora
MedGen UID:
332475
Concept ID:
C1837532
Finding
Fusion of the labia minora as a result of labial adhesions resulting in vaginal obstruction.
Elevated urinary 5-amino-4-imidazolecarboxamide-riboside level
MedGen UID:
1841814
Concept ID:
C5826483
Finding
Increased amount of 5-amino-4-imidazolecarboxamide(AICA)-riboside in the urine. AICA-riboside is the dephosphorylated counterpart of AICAR, an intermediate of de novo purine biosynthesis.
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.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
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.
Intellectual disability, profound
MedGen UID:
892508
Concept ID:
C3161330
Mental or Behavioral Dysfunction
Profound mental retardation is defined as an intelligence quotient (IQ) below 20.
Elevated erythrocyte AICA-ribotide concentration
MedGen UID:
1052575
Concept ID:
CN377901
Finding
Concentration of 5-amino-4-imidazolecarboxamide (AICA-riboside) in red blood cells is above the upper limit of normal.
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.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Brachycephaly
MedGen UID:
113165
Concept ID:
C0221356
Congenital Abnormality
An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.
Prominent metopic ridge
MedGen UID:
387953
Concept ID:
C1857949
Finding
Vertical bony ridge positioned in the midline of the forehead.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Hyponatremia
MedGen UID:
6984
Concept ID:
C0020625
Finding
An abnormally decreased sodium concentration in the blood.
Wide mouth
MedGen UID:
44238
Concept ID:
C0024433
Congenital Abnormality
Distance between the oral commissures more than 2 SD above the mean. Alternatively, an apparently increased width of the oral aperture (subjective).
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Skin dimple
MedGen UID:
661955
Concept ID:
C0578531
Finding
Skin dimples are cutaneous indentations that are the result of tethering of the skin to underlying structures (bone) causing an indentation.
Congenital blindness
MedGen UID:
2288
Concept ID:
C0005754
Congenital Abnormality
Blindness with onset at birth.
Esotropia
MedGen UID:
4550
Concept ID:
C0014877
Disease or Syndrome
A form of strabismus with one or both eyes turned inward ('crossed') to a relatively severe degree, usually defined as 10 diopters or more.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAICA-ribosiduria
Follow this link to review classifications for AICA-ribosiduria in Orphanet.

Recent clinical studies

Diagnosis

Joy P, Madhuri V, Palocaren T, Das S, Susan Cleave Abraham S, Korula S, Koshy B, Jose J, Chandran M, Danda S
Brain Dev 2022 Oct;44(9):645-649. Epub 2022 May 28 doi: 10.1016/j.braindev.2022.05.004. PMID: 35637059
Pelet A, Skopova V, Steuerwald U, Baresova V, Zarhrate M, Plaza JM, Hnizda A, Krijt M, Souckova O, Wibrand F, Andorsdóttir G, Joensen F, Sedlak D, Bleyer AJ, Kmoch S, Lyonnet S, Zikanova M
Hum Mol Genet 2019 Nov 15;28(22):3805-3814. doi: 10.1093/hmg/ddz237. PMID: 31600779
Hornik P, Vyskocilová P, Friedecký D, Adam T
J Chromatogr B Analyt Technol Biomed Life Sci 2006 Oct 20;843(1):15-9. Epub 2006 Jun 23 doi: 10.1016/j.jchromb.2006.05.020. PMID: 16798121

Prognosis

Pelet A, Skopova V, Steuerwald U, Baresova V, Zarhrate M, Plaza JM, Hnizda A, Krijt M, Souckova O, Wibrand F, Andorsdóttir G, Joensen F, Sedlak D, Bleyer AJ, Kmoch S, Lyonnet S, Zikanova M
Hum Mol Genet 2019 Nov 15;28(22):3805-3814. doi: 10.1093/hmg/ddz237. PMID: 31600779

Clinical prediction guides

Ramond F, Rio M, Héron B, Imbard A, Marie S, Billiemaz K, Denommé-Pichon AS, Kuentz P, Ceballos I, Piraud M, Vincent MF, Touraine R
J Inherit Metab Dis 2020 Nov;43(6):1254-1264. Epub 2020 Jul 9 doi: 10.1002/jimd.12274. PMID: 32557644
Pelet A, Skopova V, Steuerwald U, Baresova V, Zarhrate M, Plaza JM, Hnizda A, Krijt M, Souckova O, Wibrand F, Andorsdóttir G, Joensen F, Sedlak D, Bleyer AJ, Kmoch S, Lyonnet S, Zikanova M
Hum Mol Genet 2019 Nov 15;28(22):3805-3814. doi: 10.1093/hmg/ddz237. PMID: 31600779
Marie S, Heron B, Bitoun P, Timmerman T, Van Den Berghe G, Vincent MF
Am J Hum Genet 2004 Jun;74(6):1276-81. Epub 2004 Apr 26 doi: 10.1086/421475. PMID: 15114530Free PMC Article

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