Mucopolysaccharidosis type VI in a Miniature Poodle-type dog caused by a deletion in the arylsulphatase B gene

Abstract

AIM: To investigate and characterise an inborn error of metabolism in a dog with skeletal and ocular abnormalities.

METHODS: A 2.5-year-old small male Miniature Poodle-like dog was presented with gross joint laxity and bilateral corneal opacities. Clinical examination was augmented by routine haematology, serum chemistry, radiographs, pathology, enzymology and molecular genetic studies. Euthanasia was requested when the dog was 3 years of age because of progressively decreasing quality of life.

RESULTS: Radiology revealed generalised epiphyseal dysplasia, malformed vertebral bodies, luxation/subluxation of appendicular and lumbosacral joints with hypoplasia of the odontoid process and hyoid apparatus. These clinical and radiographic findings, together with a positive urinary Berry spot test for mucopolysaccharides, and metachromatic granules in leucocytes, were indicative of a mucopolysaccharidosis (MPS), a lysosomal storage disease. Histological lesions included vacuolation of stromal cells of the cornea, fibroblasts, chondrocytes, macrophages and renal cells. The brain was essentially normal except for moderate secondary Wallerian-type degeneration in motor and sensory tracts of the hind brain. Dermatan sulphate-uria was present and enzymology revealed negligible activity of N-acetylgalactosamine-4-sulphatase, also known as arylsulphatase B, in cultured fibroblasts and liver tissue. A novel homozygous 22 base pair (bp) deletion in exon 1 of this enzyme's gene was identified (c.103_124del), which caused aframe-shift and subsequent premature stop codon. The “Wisdom pure breed-mixed breed” test reported the dog as a cross between a Miniature and Toy Poodle.

CONCLUSIONS: The clinicopathological features are similar to those of MPS type VI as previously described in dogs, cats and other species, and this clinical diagnosis was confirmed by enzymology and molecular genetic studies. This is an autosomal recessively inherited lysosomal storage disease.

CLINICAL RELEVANCE: The prevalence of MPS VI in Miniature or Toy Poodles in New Zealand and elsewhere is currently unknown. Due to the congenital nature of the disorder, malformed pups may be subject to euthanasia without investigation and the potential genetic problem in the breed may not be fully recognised. The establishment of a molecular genetic test now permits screening for this mutation as a basis to an informed breeding policy.     

Descriptive epidemiological study of the use of antimicrobial drugs by companion animal veterinarians in New Zealand

Abstract

AIM: To describe the patterns of use of antimicrobial drugs by veterinary surgeons treating commonly presented bacterial infections in companion animals in New Zealand.

METHODS: A postal survey of 800 randomly selected companion animal veterinarians practicing in New Zealand was conducted between August and December 2008. Data were collected regarding the antimicrobials prescribed for recent cases of skin, ear and urinary tract infections; the use of culture and susceptibility testing; and veterinarian characteristics such as proportion of time spent treating companion animals and recent attendance at continuing professional development (CPD) events. Potential associations within the data were explored using extended mosaic plots and multivariable regression models.

RESULTS:Completed surveys from 393 respondents were available for analysis, providing data on systemic antimicrobial drug use for 1,799 cases of presumptive bacterial infections. The most frequently prescribed drugs were amoxicillin-clavulanic acid (864 cases, 48%), cephalexin (558, 31%), and fluoroquinolones (198, 11%). Of 359 cases of canine superficial pyoderma, 157 (44%) were treated with amoxicillin-clavulanic acid and 155 (43%) were treated with cephalexin with median reported treatment durations of 7 and 10 days, for these two drugs respectively. Culture and susceptibility tests had been used in 376 of 1,984 (19%) of all reported cases and 160 (43%) of these were suspected urinary tract infections. Practitioners that spent 100% of their time treating companion animals and who had attended a CPD course related to companion animals within the 12 months prior to completing the survey were more likely to submit a sample for culture and susceptibility testing and to prescribe longer courses of antimicrobials for the treatment of canine pyoderma than practitioners who spent less than 100% of their time treating companion animals and had not attended a CPD course in the last 12 months.

CONCLUSIONS: Broad-spectrum drugs considered by the World Health Organisation to be critically important for human health, such as fluoroquinolones and amoxicillin-clavulanic acid, are amongst the most frequently prescribed antimicrobials in companion animal medicine, and these drugs are often prescribed without submitting a sample for culture and susceptibility testing.

CLINICAL RELEVANCE: Many cases of superficial pyoderma were treated for less than the recommended duration of 21 days, which may contribute to a higher rate of recurrent pyoderma and the development of drug resistance within the causal bacteria. Veterinarians should be aware that the use of fluoroquinolones, in particular, should be based upon the results of a culture and susceptibility test.     

Prostaglandin Endoperoxide Synthase 2 (PTGS2) and Prostaglandins F2α and E2 Synthases (PGFS and PGES) Expression and Prostaglandin F2α and E2 Secretion Following Oestrogen and/or Progesterone Stimulation of the Feline Endometrium

Sex steroids in synergy with prostaglandins (PG) are involved in the regulation of cyclic ovarian function. In this study, we investigated the mRNA expression of three genes involved in arachidonic acid (AA) metabolism and hence PG production in domestic cats: PG‐endoperoxide synthase (PTGS2), PGF_2α synthase (PGFS) and PGE₂ synthase (PGES). Feline endometria (n = 16) were collected at oestrus and mid and late phases of pseudopregnancy. In addition, the effects of E₂ and/or P₄ on PG secretion and gene expression on endometrial explants were studied in an in vitro culture system. Expression levels of all examined genes were up‐regulated at the mid phase of pseudopregnancy. The effects of E₂ and/or P₄ treatment on both PG secretion and expression of the genes were observed after 12 h of culture. Expression of PGES was significantly up‐regulated by E₂ plus P₄ at oestrus and the mid phase of pseudopregnancy and was also up‐regulated by a single treatment with P₄ at late pseudopregnancy (p < 0.05). Simultaneous incubation with E₂ and P₄ up‐regulated PTGS2 gene expression at oestrus and mid‐luteal phase (p < 0.05). Progesterone plus E₂ significantly increased PGE₂ secretion at oestrus and the mid phase of pseudopregnancy. However, treatment with E₂ and/or P₄ affected neither PGF_2α secretion nor PGFS expression at any phase after 12 h of culture. The overall findings indicate that genes involved in PG synthesis are up‐regulated at the mid phase of pseudopregnancy. An increase in PGE₂ secretion and up‐regulation of PGES and PTGS2 are the main responses of the endometrium to treatment with E₂ and P₄ at oestrus and the mid phase of pseudopregnancy in the cat. These data support the hypothesis that ovarian sex steroids via endometrial PGE₂ are involved in endocrine homoeostasis, especially at oestrus and the mid, but not the late, phase of pseudopregnancy in cats.     

A Case of Successful Pregnancy in a Ewe with Uterus Didelphys

Uterus didelphys is a rare congenital abnormality of the reproductive tract. Although it occurs in various species, there are no published reports describing pregnancy outcome in association with this abnormality. Herein we describe a case of successful unilateral singleton pregnancy in a ewe incidentally found to have uterus didelphys during the course of a biomedical research study. The pregnancy was established using assisted reproductive techniques and interrupted in late gestation, at which point the abnormality was identified. Serial ultrasound assessment of foetal biometry revealed a normal foetal growth trajectory. Despite a 45% reduction in placentome number, total placentome weight was near normal secondary to compensatory placentome growth and development. To our knowledge, this is the first detailed report of normal foetal growth in an animal with uterus didelphys and illustrates the ability of the ovine placenta to adapt to a reduced number of placentomes and maintain foetal nutrient supply.     

Lactose Synthase Components in Milk: Concentrations of α-Lactalbumin and β1,4-Galactosyltransferase in Milk of Cows from Several Breeds at Various Stages of Lactation

It is believed that milk production is determined by the number and activity of mammary secretory cells. Secretory activity, as assessed by milk volume, depends on secretion of the major osmole in milk, lactose, which is produced by lactose synthase. The amount of either of the two proteins in lactose synthase may regulate milk production. The objective of this study was to determine whether the concentrations in milk of the two components of lactose synthase, α‐lactalbumin (α‐LA) and β1,4‐galactosyltransferase (B4GALT), were related to genetic background, stage of lactation, breed or parity of dairy cows. α‐Lactalbumin and B4GALT concentrations were measured by ELISA and by enzyme assays, respectively, from single milk samples. Two herds with a total of 279 cows were used in the analysis. One herd contained Ayrshire, Brown Swiss, Holstein and Jersey cows; the second herd contained two groups of cows; Holsteins selected for high milk production and Holsteins with 1960s genetics. The α‐LA concentration in milk was greater in Jerseys and Ayrshires than in Holsteins and Brown Swiss. However, no difference in α‐LA concentration was observed in milk from high and low genetic merit cows in the Minnesota herd or among different genetic backgrounds in the Illinois herd. β1,4‐Galactosyltransferase concentrations were similar for all groups that were analyzed. α‐Lactalbumin concentrations were positively correlated with milk protein concentration, milk fat concentration and lactose concentration. β1,4‐Galactosyltransferase concentration in milk exhibited a strong positive correlation with number of days in milk. Although the concentration of B4GALT increased as lactation progressed, the values did not show any correlation with persistency of lactation or late lactation milk production. In conclusion, this survey shows that the two components of lactose synthase are each correlated to protein concentration and individually correlated to the concentration of other milk components and stage of lactation.