Rationale:
Niemann-Pick type C (NPC) is an autosomal recessive lysosomal storage disease (LSD) caused by mutations in NPC1 or NPC2 genes. Mutations result in abnormal cholesterol trafficking, which is manifested by abnormal cholesterol and glycosphingolipid accumulation in lysosomes of various cells.
Presenting concerns of the patient:
The patient had a history of hyperlipidemia, hypertension, depression, and elevated alkaline phosphatase and initially presented for a workup regarding chronic kidney disease stage G3b/A3 with proteinuria of 1.9 g/day.
Diagnosis:
Kidney biopsy revealed numerous lamellar bodies (LB) in podocytes with differential diagnoses of Fabry disease (FD), nail-patella syndrome (which is associated with LMX1B gene mutations), and drug-induced phospholipidosis per pathology report. Her workup was negative for a galactosidase-alpha (GLA) mutation with normal serum and leukocyte alpha-galactosidase A activity. She was serendipitously discovered to have compound heterozygous mutations in NPC1 genes (one pathogenic and the other a variant of uncertain significance) from the comprehensive lysosomal storage gene panel as part of her genetic workup for FD. Further studies were done to determine the significance of the NPC1 mutation and revealed elevated oxysterols. (The profile was consistent with NPC, with elevated cholestane-3beta,5alpha,6beta-triol and 7-ketocholesterol and normal lyso-sphingomyelin.) Sonogram revealed hepatosplenomegaly (liver measuring 20 cm and spleen 15.8 cm). These findings in conjunction with lysosomal lipid accumulation on kidney biopsy were consistent with NPC.
Interventions:
She was on 2 cationic amphiphilic agents (CAAs), fluoxetine and atorvastatin, both of which were stopped. There was no significant difference in proteinuria 2 months off CAAs. The treatment of NPC remained supportive care and avoiding medications that can induce seizures or excessive salivary secretion.
Novel findings:
The presence of LB is classically described as a feature of FD which is an LSD. Niemann-Pick type C is another example of an LSD and is typically manifested by neurovisceral symptoms and varies by the age of onset. Renal diseases are typically not described as one of the manifestations of NPC. To our knowledge, there is only one report each for Niemann-Pick disease type A/B and NPC with LB on kidney biopsy. The finding reaffirms that the presence of LB indicates lysosomal lipid accumulation from a variety of etiologies and is not a pathognomonic finding of FD. Niemann-Pick type C should be included as one of the diseases capable of causing renal LB.