1 - Pediatrics Resident, Hospital Dona Estefânia, CHLC, Lisboa, Portugal
2 - Gastroenterology Unit. Hospital Dona Estefânia, CHLC, Lisboa, Portugal
3 - Neuropediatric Service, Hospital Dona Estefânia, CHLC, Lisboa, Portugal
4 - Neonatal Screening, Metabolism and Genetics Unit, INSA-Porto, Porto, Portugal
5 - Metabolic Diseases Reference Center, CHLC, Lisboa, Portugal
- 14º Simposio Internacional da Sociedade Portuguesa de Doenças Metabólicas (Poster). Porto, 15 a 17 de Março de 2018
Resumo:
Introduction: Niemann-Pick disease type C (NP-C) is a rare, neurovisceral lysosomal disorder caused by autosomal recessive mutations in NPC1 or NPC2 gene, which leads to a disturbance in the intracellular transport of non-esterified cholesterol and subsequent accumulation. Filipin staining of cultured skin fibroblasts has been the traditional diagnostic method. However, given the slowness and complexity in its interpretation, other biomarkers such as oxysterols, lysosphingomyelin (LysoSM) and lysosphingomyelin-509 (LysoSM-509) have been investigated and used more often in the diagnosis and follow-up of NPC patients. Miglustat is the only approved treatment and prognosis depends on the age of onset of neurological symptoms.
Case Report: A 21-month-old girl, born after 35 weeks gestation, was referred due to psychomotor development delay, alanine aminotransferase elevation and splenomegaly (probably from birth). She had slightly coarse facies, hypertrichosis, limitation in elbow and knees extension, kyphosis, difficulty in walking and recurrent otitis. In the following months she lost some language and motor skills, started with choking episodes, loss of tone with laughter and febrile seizures. Vertical supranuclear gaze palsy was difficult to assess. Extensive investigation included: normal urinary mucopolysaccharides and oligosaccharides, β-D-quitotriosidase moderately high and normal sphingomyelinase. Plasma oxysterols analysis showed an increase in cholestane-3b,5a,6b-triol and 7-ketocholesterol leading to the diagnosis of NP-C disease, confirmed later on by the presence of a mutation in homozygosity in the NPC1 gene. After initiation of therapy with miglustat, 8 months ago, it was observed stabilization in neurologic progression and some improvement in language and muscle tone.
Comments: The determination of oxysterols in plasma allowed a faster diagnosis and a more rapid initiation of therapy with miglustat, along with the possibility of follow-up. In spite of this, prognosis is poor in this patient due to early onset of neurologic symptoms.