Abnormal Newborn Screening Resembling Carnitine Palmitoyltransferase 1a Deficiency in Three Patients With COASY...

COASY protein associated neurodegeneration is a rare, progressive autosomal recessive neuroferritinopathy due to pathogenic mutations in the COASY gene, coding for the mitochondrial located coenzyme A synthase. Clinical manifestations include seizures, progressive spasticity, dystonia, neuropathy, cognitive decline and neuropsychiatric abnormalities. Both foetal and childhood onset phenotypes are described. We report three patients with COASY protein associated neurodegeneration who were identified on newborn screening with a dried bloodspot acylcarnitine pattern consistent with carnitine palmitoyltransferase 1a deficiency, that is, an elevated ratio of free carnitine (C0) to the sum of palmitoylcarnitine (C16) and octanoylcarnitine (C18):[C0/(C16+C18)]. Two siblings, who died in infancy, displayed neurological features from birth, with magnetic resonance imaging of the brain displaying immature cortical sulcation, parenchymal atrophy and pontocerebellar hypoplasia. The third patient presented with global developmental delay, pyramidal signs and seizures with brain magnetic resonance imaging at age 15 months demonstrating a thin corpus callosum, symmetric diffusion restriction throughout the basal ganglia and evidence of deposition in the globus pallidus. This report demonstrates that phenotypes of COASY protein associated neurodegeneration should be included in the differential diagnosis of dried blood spot acylcarnitine pattern suggestive of carnitine palmitoyltransferase 1a deficiency and may represent new potential for early diagnosis.