[P1-172] A girl with methylmalonic aciduria and Niemann-Pick disease type B
[Objective] Both of methylmalonic aciduria and Niemann-Pick didsease are rare inherited metabolic diseases. In this study, two rare diseases were found in a Chinese girl. [Method] The patient presented with feeding difficulty, development retardation from neonatal period. Isolated methylmalonic aciduria was diagnosed at the age of 3 years by urine organic acid analysis. After treatment by vitamin B12 and L-carnitine, significantly clinical improvement was observed, indicating the diagnosis of vitamin B12-responsive methylmalonic aciduria. For the genetic study, next generation gene sequencing was performed at the age of 3 years and 2months of the patient. [Results] On her MUT gene, two mutations (c.1540C>A and c.323G>A) were identified, supporting the diagnosis of methylmalonyl CoA mutase deficient methylmalonic aciduria. But surprisingly, two mutations (c.1144C>T and c.1675G>T) on the SMPD1 gene were found in the patient. Markedly reduced peripheral blood leucocytes lysosomal acid sphingomyelinase activity (80.8 nmol/g/min vs normal control 216.1 to 950.9 nmol/g/min) confirmed the diagnosis of Niemann-Pick disease. Moderate splenomegaly and typical"sea-blue histiocytes" in her bone marrow were also observed. [Conclusion] Although most of the inherited metabolic disorders are rare, two or more disorders occurred simultaneously in some cases. In this study, a girl with two rare diseases of methylmalonic aciduria and Niemann-Pick disease type B was diagnosed by biochemical assay and next generation gene sequencing. Carefully clinical and laboratory studies are keys to reach the precision medcine.