Feline Niemann-Pick Disease With a Novel Mutation of SMPD1 Gene

Abstract

<jats:p> A 4-month-old female mixed-breed cat showed gait disturbance and eventual dysstasia with intention tremor and died at 14 months of age. Postmortem histological analysis revealed degeneration of neuronal cells, alveolar epithelial cells, hepatocytes, and renal tubular epithelial cells. Infiltration of macrophages was observed in the nervous system and visceral organs. The cytoplasm of neuronal cells was filled with Luxol fast blue (LFB)-negative and periodic acid-Schiff (PAS)-negative granules, and the cytoplasm of macrophages was LFB-positive and PAS-negative. Ultrastructurally, concentric deposits were observed in the brain and visceral organs. Genetic and biochemical analysis revealed a nonsense mutation (c.1017G&gt;A) in the SMPD1 gene, a decrease of SMPD1 mRNA expression, and reduced acid sphingomyelinase immunoreactivity. Therefore, this cat was diagnosed as having Niemann-Pick disease with a mutation in the SMPD1 gene, a syndrome analogous to human Niemann-Pick disease type A. </jats:p>

Novel Mutation in the Feline NPC2 Gene in Cats with Niemann–Pick Disease

“…Sequence data were obtained from the two affected cats and four clinically healthy JD cats. Before analyzing NPC1 and NPC2 in the two cats, we confirmed the absence of the SMPD1:c.1017G>A (p.W339*) mutation, which causes NP type A [20].…”

“…Postmortem, the disease proved to be neurovisceral NP with an accumulation of sphingomyelin and cholesterol based on lipid analysis, histopathology, and electron microscopy [19]. The clinical, biochemical, and histopathological characteristics of these two cats with NP were similar to those of NPC rather than those of NP type A. Consequently, we analyzed the feline NPC1 and NPC2 genes after confirming the absence of the SMPD1:c.1017G>A (p.W339*) mutation that was recently reported in a Siamese cat with NP type A [20].…”

“…In Japan, a Siamese cat and a Japanese domestic (JD) cat suspected of having NPC were described in 1989 [16][17][18] and 1998 [19], respectively. Recently, another Siamese cat was diagnosed with NP and proven to be affected by NP type A because the cat was homozygous for a novel nonsense mutation (SMPD1:c.1017G>A (p.W339*)) [20]. The first two cases were diagnosed as NP based on clinical manifestations and histopathological, ultrastructural, and tissue biochemical analyses, which were very similar to those of human and feline NPC cases [16][17][18].…”