Epileptic encephalopathy with microcephaly in a patient with asparagine synthetase deficiency: a video-EEG report.

Asparagine synthetase deficiency is a rare autosomal recessive neurometabolic disorder caused by mutations in the asparagine synthetase gene. It is characterized by congenital microcephaly, intellectual disability, progressive cerebral atrophy, and intractable seizures. A decrease in asparagine in CSF or plasma guides subsequent investigations in some cases, but normal values are described in other cases. Therefore, reaching a diagnosis is challenging and relies on exome sequencing. We report the case of a child with progressive microcephaly, irritability, startle reflexes, and jitteriness since birth. Focal clonic and myoclonic seizures, status epilepticus, and infantile spasms appeared in the first months of life. At first, the EEG showed multifocal epileptic activity which later turned into modified hypsarrhythmia and discontinuous activity. Brain MRI showed brain atrophy, a simplified gyral pattern, and poor myelination. Plasma asparagine levels were normal. Due to remote parental consanguinity, a study of contiguous regions of runs of homozygosity was performed, showing a 5-Mb region (chr7:95629078-100679007) including the asparagine synthetase gene. The molecular analysis of this gene led to identification of a novel homozygous missense mutation, c.761G>T(p.Gly254Val), in our patient. The peculiar electroclinical phenotype may lead to diagnostic suspicion and molecular analysis which may benefit genetic counselling. [Published with video sequence].

Acute psychosis in an adolescent with undiagnosed homocystinuria.

Homocystinuria due to cystathionine-ß-synthase deficiency (CBS deficiency) usually presents with ectopia lentis, myopia, intellectual disability, skeletal anomalies resembling Marfan syndrome, and thromboembolic events. Whereas neurodevelopment impairments have been often described in untreated homocystinuria adult patients, acute psychosis has rarely been reported as a presenting symptom of the disease. Here, we describe a 17-year-old girl affected by CBS deficiency presenting acute onset of visual hallucinations, behavioral perseverance, psychomotor hyperactivity, and affective inappropriateness. Ectopia lentis, diagnosed several years before, didn't have been considered as possible sign of a metabolic disorder. Psychotic symptoms were unresponsive to the conventional antipsychotic drugs and relieved after pyridoxine and folic acid treatment. CONCLUSION: A diagnosis of homocystinuria due to CBS deficiency should be considered in patients presenting, as target signs, ectopia lentis with or without learning difficulties, and should also be taken into account as a potentially treatable cause of acute psychosis in childhood and adolescence. WHAT IS KNOWN: • Homocystinuria frequently present with ectopia lentis, myopia, cognitive impairment, Marfan-like phenotype, osteoporosis, cerebrovascular, or cardiac thrombosis. • Acute psychosis has rarely been reported as a presenting symptom of the disease. WHAT IS NEW: • The complete psychotic symptoms' remission with pharmacological doses of pyridoxine and folic acid, without antipsychotic drugs.