An unusual case of Cardiobacterium valvarum causing aortic endograft infection and osteomyelitis.

BACKGROUND: HACEK (Haemophilus spp., Aggregatibacter spp., Cardiobacterium spp., Eikenella corrodens, and Kingella spp.) group organisms are responsible for 0.8% to 6% of all infective endocarditis cases, with Cardiobacterium spp. being the third most commonly implicated HACEK microorganism. Within this genus is Cardiobacterium valvarum (C. valvarum), a novel organism described in 2004. To date, only 15 cases of C. valvarum infection have been reported in the English-language literature, and have primarily been cases of infective endocarditis in patients with valvular disease. C. valvarum has not been reported to cause infections spreading to the surrounding bone. CASE PRESENTATION: We present a case of a 57-year-old man with a history of aortic dissection followed by aortic endograft replacement who presented with back pain. He was found to have radiographic evidence of an infected aortic endograft, along with vertebral osteomyelitis, discitis, and epidural phlegmon. Blood cultures identified C. valvarum as the causative organism. The patient was treated with ceftriaxone and surgical intervention was deferred due to the patient's complex anatomy. His course was complicated by septic cerebral emboli resulting in cerebrovascular accident. CONCLUSIONS: This case report highlights C. valvarum, a rare and emerging HACEK group microorganism that warrants consideration in high-risk patients with evidence of subacute infection and disseminated disease. While C. valvarum classically presents as infective endocarditis, extra-cardiac manifestations have also been described. As demonstrated in this case, endograft involvement and osteomyelitis may occur in rare circumstances.

Inheritance of lysosomal acid beta-galactosidase activity and gangliosides in crosses of DBA/2J and knockout mice.

GM1 gangliosidosis is a progressive neurodegenerative disease caused by deficiencies in lysosomal acid beta-galactosidase (beta-gal) and involves accumulation and storage of ganglioside GM1 and its asialo form (GA1) in brain and visceral tissues. Similar to the infantile/juvenile human disease forms, B6/129Sv beta-gal knockout (ko) mice express residual tissue beta-gal activity and significant elevations of brain GM1, GA1, and total gangliosides. Previous studies suggested that inbred DBA/2J (D2) mice may model a mild form of the human disease since total brain ganglioside and GM1 concentration is higher while beta-gal specific activity is lower (by 70-80%) in D2 mice than in inbred C57BL/6J (B6) mice and other mouse strains. A developmental genetic analysis was conducted to determine if the genes encoding beta-gal (Bgl) in the D2 and the ko mice were functionally allelic and if the reduced brain beta-gal activity in D2 mice could account for elevations in total brain gangliosides and GM1. Crosses were made between D2 mice homozygous for the Bgld allele (d/d), and either B6/129Sv mice heterozygous for the Bgl+ allele (+/-) or homozygous for the ko Bgl- allele (-/-) to generate d/+ and d/- mice. Specific beta-gal activity (nmol/mg protein/h) showed additive inheritance in brain, liver, and kidney at juvenile (21 days) and adult (255 days) ages with the d/- mice having only about 16% of the beta-gal activity as that in the +/+ mice. These results indicate that the Bgl genes in the D2 and the ko mice are noncomplementing functional alleles. However, the d/- mice did not express GA1 and had total brain ganglioside and GM1 concentrations similar to those in the d/+ and +/+ mice. These results suggest that the reduced brain beta-gal activity alone cannot account for the elevation of total brain gangliosides and GM1 in the D2 mice.

N-butyldeoxygalactonojirimycin reduces neonatal brain ganglioside content in a mouse model of GM1 gangliosidosis.

GM1 gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid beta-galactosidase (beta-gal), the enzyme that catabolyzes GM1 within lysosomes. Accumulation of GM1 and its asialo form (GA1) occurs primarily in the brain, leading to progressive neurodegeneration and brain dysfunction. Substrate reduction therapy aims to decrease the rate of GSL biosynthesis to counterbalance the impaired rate of catabolism. The imino sugar N-butyldeoxygalactonojirimycin (NB-DGJ) is a competitive inhibitor of the ceramide-specific glucosyltransferase that catalyzes the first step in GSL biosynthesis. Neonatal C57BL/6J (B6) and beta-gal knockout (-/-) mice were injected daily from post-natal day 2 (p-2) to p-5 with either vehicle or NB-DGJ at 600 mg or 1200 mg/kg body weight. These drug concentrations significantly reduced total brain ganglioside and GM1 content in the B6 and the beta-gal (-/-) mice. Drug treatment had no significant effect on viability, body weight, brain weight, or brain water content in the B6 and beta-gal (-/-) mice. Significant elevations in neutral lipids (GA1, ceramide, and sphingomyelin) were observed in the NB-DGJ-treated beta-gal (-/-) mice, but were not associated with adverse effects. Also, NB-DGJ treatment of B6 and beta-gal (-/-) mice from p-2 to p-5 had no subsequent effect on brain ganglioside content at p-21. Our results show that NB-DGJ is effective in reducing total brain ganglioside and GM1 content at early neonatal ages. These findings suggest that substrate reduction therapy using NB-DGJ may be an effective early intervention for GM1 gangliosidosis and possibly other GSL lysosomal storage diseases.