Towards a suggestive facial dysmorphism in adenylosuccinate lyase deficiency?

Adenylosuccinate lyase deficiency (MIM 103050, ADSL) is a rare autosomal recessive disease causing severe mental retardation and/or autistic features. 2 Seizures are often observed (80%), varying in age of onset (from newborn to late childhood) and nature (tonic-clonic, “suppression burst” pattern, West syndrome, etc), and are very often resistant to all medication. Around 50% of the children show autistic-like behaviour. Microcephaly is rare (1/13 of reported cases). Non-specific anomalies of the brain, such as hypoplasia of the vermis, cerebral atrophy, lack of myelination, white matter anomalies, and lissencephaly have often been described. ADSL is a homotetramer involved in two distinct steps of purine synthesis, namely (1) the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) into aminoimidazole carboxamide ribotide (AICAR), and (2) the conversion of adenylosuccinate (S-AMP) into adenosine monophosphate (AMP) in the inosine monophosphate transformation pathway (fig 1). The diagnosis of ADSL deficiency is based on the detection of dephosphorylated SAICAR and S-AMP products, that is, S-Ado (succinyladenosine) and SAICAr (succinylaminoimidazole carboxamide riboside). The modified BrattonMarshall test is the most convenient urinary screening test, 9 but conclusive diagnosis requires the identification of S-Ado and SAICAr in urine or cerebrospinal fluid by high performance liquid chromatography (HPLC). The gene for adenylosuccinate lyase has been mapped to chromosome 22q13.1-q13.2 and around 20 different missense mutations and one deletion have been identified so far. Most patients are compound heterozygotes. Here, we report on a novel case of adenylosuccinate lyase deficiency, sharing a number of clinical features with previously reported cases, and emphasise the facial dysmorphic features hitherto unreported in this condition.