Heavy on the Foam: A Presentation of Niemann-pick Disease in a Teenager

Introduction: Many genetic disorders manifest at birth or in early childhood. However certain conditions with milder phenotypes may present in adolescence and should be considered in relevant clinical scenarios. The following case describes an adolescent patient with a constellation of progressive symptoms who was ultimately diagnosed with Niemann-Pick Disease type B.

Case Description: A 17-year-old female with mild intellectual disability presented to the emergency department with worsening generalized abdominal pain. She had been experiencing intermittent abdominal discomfort and fullness, in addition to fatigue, fevers, and extremity pain, over the preceding year. She also reported chest pain and dry cough. The patient’s examination was notable for a tender and distended abdomen with palpable hepatosplenomegaly. She also had short stature and bony tenderness throughout her lower extremities. Diagnostic studies revealed leukopenia (2.7 x 10^9/L), thrombocytopenia (135 x 10^9/L), coagulopathy (PT 14 sec, PTT 73 sec), and elevated liver enzymes (AST 145 IU/L, ALT 204 IU/L). Her lipid profile was abnormal (total cholesterol 449 mg/dL, triglycerides 541 mg/dL). Abdominal imaging showed hepatosplenomegaly and chest imaging demonstrated reticular infiltrates in the lungs. Liver biopsy revealed microvesicular steatosis and foamy macrophages. Foam cells were also detected in the bone marrow. Lysosomal enzyme screening showed low levels of sphingomyelinase activity, and a next-generation sequencing based lysosomal storage disorder panel detected a homozygous pathogenic variant in the gene that encodes sphingomyelin phosphodiesterase 1 (SMPD1). She was subsequently diagnosed with Niemann-Pick Disease (NPD) type B.

Discussion: NPD is an autosomal recessive condition characterized by sphingomyelinase deficiency and resulting accumulation of lipid laden cells in the liver, spleen, lungs and bone marrow. This patient’s clinical features are consistent with NPD type B, which generally presents late in childhood as progressive hypersplenism, liver dysfunction, interstitial lung disease and abnormal skeletal growth. Variable CNS involvement can manifest as intellectual disability. In comparison to NPD type A, the delayed presentation of NPD type B may be related to its association with variants of SMPD1 that yield a small amount of residual enzymatic activity. Genetic and enzymatic testing are required to confirm the diagnosis.

Conclusion: This case describes a teenage patient with progressive abdominal pain who was diagnosed with NPD type B one year after the emergence of her symptoms. Early consideration of NPD type B in adolescents may facilitate more timely diagnoses. Though there is no curative therapy, individuals with NPD type B may benefit from multidisciplinary care to support their survival into adulthood.