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To date only 4 affected individuals from 3 independent families have been reported worldwide.

There are no specific fetal abnormalities. However, during pregnancy, intrauterine growth retardation and low amniotic fluid are noted frequently. The newborns usually display a marked global hypotonia and global developmental delay is usually noticeable during the first year. Affected children are able to learn some skills but most of them will remain unable to walk and speak. No structural brain abnormalities are noted. Epilepsy of variable type and severity is frequent and usually noticeable during the first year of life. Visual issues are also usually noticeable during the first year of life, characterized mainly by severe hypermetropia and chorio-retinal atrophy. Some individuals can see close objects whereas others are blind. Severe scoliosis usually appears during childhood. Growth remains delayed to approximately -2 to -4 standard deviations, with normal cranial circumference. Affected individuals share common inconspicuous facial features (short and upturned nose, brushy eyebrows, and long eyelashes). Other clinical features that may be related to the disease include chronic hepatic cytolysis with recurrent acute aggravations and hepatomegaly , aortic coarctation of the newborn, and nephrocalcinosis. A less severe phenotype is possible.

AICA-ribosiduria is caused by germline defects in the ATIC gene (2q35). The pathogenesis seems to involve a cytotoxic effect of abnormally accumulated substrates of ATIC enzyme: AICAR and AICA-riboside. No genotype-phenotype relationship has been identified.

The diagnostic is not usually suspected on clinical grounds, although theoretically recognizable. It is more realistically suspected after exome-, genome-, or gene-panel- sequencing, in the presence of two pathogenic loss of function variations in the gene ATIC, with a bi-allelic pattern. The diagnosis can also be suspected in the presence of a positive urine Bratton-Marshall test suggesting an accumulation AICA-riboside. The diagnosis may be definitively confirmed by HPLC (High Performance Liquid Chromatography) analysis.

There is no true differential diagnosis. However, each of the core features has numerous differential diagnoses.

Prenatal diagnosis is possible where the pathogenic variants have been previously identified in a family member.

The pattern of inheritance is autosomal recessive. For the parents of an affected child, the risk of recurrence for each future pregnancy is 25%. Genetic counseling is highly recommended for affected families.

Management is multidisciplinary. There is no preventive, curative, or specific treatment to date. Epilepsy should be sought, and when present should be treated by an experienced neuropediatrician according to the standard protocols. It may become pharmacoresistant. The patient should be referred to an experienced ophthalmologist. Hypermetropia can be treated according to standard procedures; however, chorio-retinal atrophy has no specific treatment. The presence of scoliosis should be assessed and treated aggressively if present. Neurodevelopment should be supported through an early intervention program. Growth retardation is not usually subject to specific measures.

To date all individuals affected by AICA-ribosiduria require extensive support. Life expectancy is unknown (oldest individual is 20 years of age).