Case report of a rare purine synthesis disorder due to 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICAR) deficiency.

BACKGROUND: AICA (5-aminoimidazole-4-carboxamide) ribosiduria is an inborn error in purine biosynthesis caused due to biallelic pathogenic variants in the 5-aminoimidazole-4-carboxamide ribonucleotide-formyltransferase/imp cyclohydrolase (ATIC) gene located on chromosome 2q35. ATIC codes for a bifunctional enzyme, AICAR transformylase and inosine monophosphate (IMP) cyclohydrolase, which catalyse the last two steps of de novo purine synthesis. This disorder has been previously reported in only 4 cases worldwide, and herein, we report the first from India. CASE REPORT: The proband presented with global developmental delay, developmental hip dysplasia (DDH), acyanotic heart disease and nystagmoid eye movements. Whole exome sequencing (WES) identified compound heterozygous pathogenic variants in the ATIC. A novel splice site variant; c.1321-2A > G and a previously reported missense variant; c.1277A > G (p.Lys426Arg) were identified. Segregation analysis of parents showed the father to be a heterozygous carrier for the splice site variant and the mother, a heterozygous carrier for the missense variant. CONCLUSION: This case of a rare genetic disorder of purine biosynthesis of ATIC deficiency is the first case reported from India. Early diagnosis lead to early interventional therapy and genetic counselling.

Novel Imaging Finding and Novel Mutation in an Infant with Molybdenum Cofactor Deficiency, a Mimicker of Hypoxic-Ischaemic Encephalopathy.

Molybdenum cofactor deficiency is a rare metabolic disorder manifesting with early onset seizures, developmental delay, microcephaly, and spasticity. In this report, we describe a three-month-old infant with neonatal onset, poorly controlled seizures, developmental delay, microcephaly, spastic quadriparesis and visual insufficiency. Magnetic resonance imaging of brain had shown cystic encephalomalacia involving bilateral parieto-occipital lobe and elevated lactate in magnetic resonance spectroscopy. Restricted diffusion noted along the corticospinal tract in our case is a novel imaging finding in patients with molybdenum cofactor deficiency. Low serum uric acid and elevated urine sulfite excretion were observed. A novel homozygous mutation was detected in exon 4 of molybdenum cofactor synthesis 2 (MOCS2) gene. Early infantile or neonatal onset seizures, developmental delay, microcephaly and cystic encephalomalacia in neuroimaging mimicking hypoxic-ischaemic encephalopathy should raise the suspect for molybdenum cofactor deficiency. Screening of all neonates for urinary sulfite metabolites would help in early diagnosis and management. Early diagnosis and treatment with cyclic pyranopterin monophosphate could arrest the progression of molybdenum cofactor deficiency type A. More research is needed to explore further treatment options in this otherwise lethal disorder.