PP03.10 – 2967: Niemann-Pick C disease: Diagnostic challenge

Abstract

Introduction Niemann-Pick C Disease (NPCD) is an autosomal recessive storage lipidosis due to a disorder of cholesterol esterification leading to the accumulation of sphingomyelin and cholesterol in the brain, liver and spleen. The heterogeneous clinical presentation of NPCD makes diagnosis difficult. We report a case of late-infantile NPCD in a child with prolonged neonatal jaundice followed by psychomotor regression at the age of 2 and white matter abnormalities. Clinical case We present a 4-year-old boy with progressive neurological regression. He was born by caesarean at term to a consanguineous family. Apgar was normal. During the neonatal period, a severe jaundice was treated by several exsanguinous transfusions. He presented a mild motor and language delay, but experienced a severe neurological regression at the age of 2. At presentation, the child had axial hypotonia, spastic quadriplegia, strabismus, failure to thrive with swallowing disorder and dysmorphic features. He subsequently developed seizures. Sequential brain MRI's showed progressive white matter involvement with a decrease in volume and signal hyperintensity on T2-weighted images, a thinning of corpus callosum and a large pituitary gland. Abdominal ultrasound detected a globular spleen without liver or spleen enlargement. Routine laboratory biochemistry profiles showed elevated aspartate aminotransferase (ASAT) activity. Nerve conduction velocities displayed a demyelinating polyneuropathy. Bone-marrow examination revealed the presence of foam cells, suggestive of NPCD. The culture of skin fibroblasts in lipid-deficient medium, using filipin stain, showed the presence of dark punctate granules, confirming the diagnosis of NPCD. Sequencing analysis showed a homozygous mutation c.1340A>G in NPC-1 gene. Conclusions This case illustrates a late-onset infantile form of Niemann-Pick C disease. We should consider NPCD as a diagnosis possibility in any patient with neonatal jaundice and psychomotor regression, especially if there is white matter involvement. Careful clinical history and bone marrow analysis were helpful to the diagnosis.