Case Report: Niemann-Pick Disease Type C (NPC) due to E20X variant in NPC2: First Case Report in Latin America

NPC2 is a rare, progressive, debilitating, and irreversible disease caused by neurovisceral lysosomal storage with the accumulation of unesterified cholesterol, sphingosine, and glycosphingolipids. It can be caused by variants in one of two genes, NPC1 or NPC2. The latter is compromised only in 5% of cases, with only about 16 cases reported with onset in early childhood and only 6 of them with the c.58GT(p.E20X) variant. The first case of a patient in Latin America (LA) with this variant is described.

Case:

4-month-old female born to consanguineous parents in Bogotá with a maternal history of four abortions but no other pre or perinatal risks.

Findings:

History of hepatocellular jaundice from the 5th day of life and progressive hepatomegaly with nonspecific liver biopsy. Persistent respiratory symptoms with ground-glass opacities in relation to alveolar proteinosis began at 3 months of age. A storage disease, specifically NPC2, was suspected so the patient was referred to neurology with hypotonia mild muscle hypotrophy, without developmental delay or other neurological signs.

Timeline:

STORCH, as well as many other IEMs, were ruled out due to the liver condition. Bronchoalveolar lavage was performed by pulmonology with confirmation of alveolar cholesterol infiltrates. Increased lysosphingomyelin-509 was found: 14,980 nMol/L (837-3,321). NGS of the NPC1/NPC2 genes confirmed a pathogenic homozygous variant in exon 1 c.58GT(p.Glu20Ter) in NPC2 confirming the disease.

Symptoms related to visceromegaly, failure to thrive, and respiratory symptoms predominated. The course was rapidly progressive, with evolution to respiratory failure and death at 6 months of age.

This first case in LA of early infantile NPC2 by c.58GT(p.E20X) had a catastrophic course in which hepatic and pulmonary compromise predominated, with little neurological compromise. NPC has a variable clinical presentation but includes mainly neurological and visceral symptoms. This case illustrates the importance of early suspicion of the condition in patients with unclear hepatomegaly and visceral symptoms, even in the absence of neurological compromise. A small number of patients present with symptoms in early childhood, almost always dying within the first year of life.