Clinical Phenotype of X‐Linked Myotubular Myopathy in Labrador Retriever Puppies

Background

Seven male Labrador Retriever puppies from 3 different litters, born to clinically normal dams and sires, were evaluated for progressive weakness and muscle atrophy. Muscle biopsies identified a congenital myopathy with pathologic features consistent with myotubular myopathy. Further investigations identified a pathogenic mutation in the myotubularin gene, confirming that these puppies had X‐linked myotubular myopathy (XLMTM).

Objective

To review the clinical phenotype, electrodiagnostic and laboratory features of XLMTM in this cohort of Labrador Retrievers.

Results

Male puppies with XLMTM were small and thin compared with their normal littermates. Generalized weakness and muscle atrophy were present by 7 weeks of age in some puppies and evident to most owners by 14 weeks of age. Affected puppies stood with an arched spine and low head carriage, and walked with a short, choppy stride. Muscle atrophy was severe and progressive. Patellar reflexes were absent. Laryngeal and esophageal dysfunction, and weakness of the masticatory muscles occurred in puppies surviving beyond 4 months of age. Serum creatine kinase activity was normal or only mildly increased. EMG findings were nonspecific and included positive sharp waves and fibrillation potentials. Clinical signs progressed rapidly, with most affected puppies unable to walk within 3–4 weeks after clinical signs were first noticed.

Conclusions and Clinical Importance

Although initial clinical signs of XLMTM are similar to the phenotypically milder centronuclear myopathy in Labrador Retrievers, XLMTM is a rapidly progressive and fatal myopathy. Clinicians should be aware of these 2 distinct myopathies with similar clinical presentations in the Labrador retriever breed.     

Fanconi Syndrome in a Labrador Retriever

A 2-year-old male Labrador Retriever was presented to the University of Missouri Veterinary Teaching Hospital with the primary complaints of polydipsia, polyuria, and joint or muscle pain. Low blood urea nitrogen concentration, hyperchloremia, and marked proteinuria were the only abnormalities in a serum biochemical profile and urinalysis. Decreased creatinine clearance and increased renal fractional excretion of sodium, potassium, calcium, and phosphorus were detected by renal clearance studies. Increased excretion of most amino acids was found by amino acid analysis of urine, but not all amino acids were lost with equal magnitude. Amino acids with secondary amino groups or basic side chains were lost at increased rates, whereas those with acidic side chains were not. These differences could be related to defects in specific renal amino acid transport mechanisms. Identification of these transport mechanisms may allow for pharmacologic intervention at the point of renal loss to alleviate clinical signs of disease.     

Neuronal ceroid-lipofuscinosis in a Labrador Retriever.

An 8-year-old Labrador Retriever with an 11-month history of progressive partial seizures and necropsy examination findings characteristic of the lamellar form of canine neuronal ceroid-lipofuscinosis (NCL) is presented. The clinical, light microscopic, and ultrastructural features of this case most closely resemble human adult-onset NCL (Kufs disease). This is the first report of NCL occurring in the Labrador Retriever breed.     

Congenital Tremor With Spongy Degeneration of the Central Nervous System in Two Puppies

Two crossbred puppies exhibited a generalized tremor that was accentuated by excitement or voluntary movement. Hypermetria was also present. Neurohistologic examination showed a bilaterally symmetric spongy condition, predominantly of the gray matter in the brain and spinal cord. These two dogs were different, both in their clinical presentation and histologic appearance, from other reported cases of spongy degeneration. The clinicopathologic correlation between spongy degeneration and tremor is unclear. Spongy degeneration should be included in the differential diagnosis of tremor syndromes in puppies.     

Penetrating ocular gunshot injury in a Labrador Retriever

A 3½‐year‐old, female (spayed) working black Labrador Retriever was referred to the Unit of Comparative Ophthalmology at the Animal Health Trust after a penetrating lead gunshot injury to the right eye. Clinical examination revealed penetrating injuries to the right cornea, left lateral canthus, and left forelimb. Radiography revealed the presence of multiple metallic foreign bodies in the head and one in the left forelimb. B‐mode ocular ultrasonography confirmed the presence of an intraocular metallic foreign body within the posterior tunics of the right eye. Medical treatment of the right eye over a period of 1 month resulted in a comfortable, visual eye. Long‐term follow‐up over 4½ years revealed a slow deterioration in vision because of progressive lens opacification and the presence of a localized area of chorioretinopathy.     

Association between Aortoseptal Angle in Golden Retriever Puppies and Subaortic Stenosis in Adulthood

Background

Predicting subaortic stenosis (SAS) in adult Golden Retriever dogs (GRs) by evaluating them as puppies is hampered by the progressive expression of the SAS phenotype in youth. In some children who develop SAS as adults, an abnormal aortoseptal angle (AoSA) precedes development of stenosis.

Objectives

To determine the normal AoSA in young adult GRs using echocardiography; to assess the value of AoSA in GR puppies for predicting development of the SAS phenotype.

Animals

Forty‐eight 2‐ to 6‐month‐old GR puppies.

Methods

Prospective study. Puppies were recruited from clients and breeders. Puppies were evaluated with a physical examination and an echocardiogram, and this evaluation was repeated when they were 12–18‐month‐old adults. Puppies were classified as unaffected (WNL) or affected (SAS) retroactively, based on their results as adults.

Results

In WNL young adult GRs, mean ± SD AoSA was 152.3 ± 6.5°. Mean ± SD AoSA in SAS puppies (144.9 ± 8.6°) was significantly different from mean AoSA in WNL puppies (155.7 ± 8.8°, P < .01). No puppy with AoSA >160° had the SAS phenotype as a young adult; 93% (75.7–99.1%) of puppies with AoSA <145° had the SAS phenotype as young adults. Peak LVOT velocity increased significantly between evaluations (P < .0001) whereas AoSA did not (P = .45).

Conclusion and Clinical Significance

A steep AoSA in GR puppies is associated with the SAS phenotype in young adulthood. Some GR puppies have an abnormal AoSA that persists in young adulthood and is detectable before peak LVOT velocity reaches levels consistent with SAS.     

Primary conjunctival mast cell tumor in a Labrador Retriever

A 4-year-old, intact male Labrador Retriever with a rapidly progressive conjunctival mass was evaluated. Ocular examination showed a 2-cm elongated mass arising from the superior bulbar conjunctiva of the left eye. The mass resulted in distortion of the palpebral fissure and contacted the superior aspect of the cornea without modifying its structure; no adhesion to the sclera was detected. The superior palpebral conjunctiva was unaffected, and the remaining ocular examination was normal. The initial diagnostic work-up included CBC, serum biochemical analysis, urinalysis, and fine needle biopsy of the mass. A poorly differentiated mast cell tumor was diagnosed by cytology. Immunocytochemistry was performed to evaluate Ki-67 proliferation index, and 54/1000 tumoral nuclei showed a dark red staining. After a complete clinical staging, the mass was excised and identified histologically as a grade-II mast cell tumor. An adjuvant treatment with prednisone and vinblastine was instituted because of the limited excisional margins. No evidence of local recurrence or metastasis has been apparent during the 29-month follow-up period. This report contributes to the current literature pertaining to canine conjunctival mast cell tumors; unfortunately, the paucity of case reports and the absence of large studies regarding this tumor make conclusions regarding its biologic behavior impossible.     

Endoscopic transcervical intrauterine artificial insemination in Labrador Retriever bitches

Besides post-thawing reduced semen quality, there are some difficulties in the execution of the endoscopic transcervical intrauterine artificial insemination (AI) with frozen-thawed semen in bitches. Therefore, the aims of the present study were to evaluate behavioral and reproductive parameters (i.e., vaginal cytology and serum progesterone level) to determine time of insemination and to investigate the particularities and difficulties of this technique in bitches using fresh semen. Ten Labrador Retriever bitches were submitted to three endoscopic transcervical intrauterine AIs (with 48 h intervals). Oestrus and ovulation period were established by behaviour evaluation, progesterone assays and vaginal cytology, enabling optimal timing for AI during oestrus. During AI, the following aspects were evaluated: cervical os catheterization difficulty, semen deposition resistance, occurrence of semen backflow, and time required to perform the AI. In this study, it was possible to catheterize the cervical os in all bitches, with different degrees of difficulty, by manipulating the equipment to allow cervical visualization and catheter introduction in the cervical canal. Serial serum progesterone assays enabled estimation of LH surge day, and thus of ovulation. The pregnancy rate was 90%, with a litter size of 5.0 ± 2.6 puppies per bitch. It was concluded that the difficulties in the execution of the endoscopic transcervical intrauterine AI technique in Labrador Retriever bitches were minimized by the equipment manipulation and practical experience.     

Change in intraocular pressure during maturation in Labrador Retriever dogs

Objective To measure intraocular pressure (IOP) in a group of dogs as puppies and young adults to determine if there is any change during maturation. Animals studied Thirty‐two healthy Labrador Retriever dogs. Procedures Intraocular pressure was measured using a Tonopen XL initially at approximately 6 weeks of age (T1), then again approximately 1 year later (T2). Exact ages were known based on whelp date. Results The dogs had marginally higher IOP OU at T2 (mean = 14.9 mmHg) compared to T1 (mean = 13.4 mmHg). However, the difference was not statistically significant. No differences were seen based on sex and litter. Intraocular pressure OD was statistically greater than OS at T1 but not at T2. Conclusions Normal values for intraocular pressure are the same in puppies and adults. The results of this study do not support the previously suggested theory that younger dogs have sustained increased IOP as a requirement to drive growth of the globe. However, it does not rule out the possibility that a dynamic relationship between intraocular pressure and expansion of the globe may exist.     

Granulomatous lymphadenitis caused by Talaromyces helicus in a Labrador Retriever

A 3-year-old spayed female Labrador Retriever was presented for right prescapular lymphadenomegaly. Examination of fine-needle aspirates and impression smears of the node revealed many short hyphal structures found within macrophages and extracellularly. Hyphae were approximately 3 μm in diameter, were irregularly septate with nonparallel walls, and had a small clear halo surrounding a partially stained basophilic internal structure. Hyphae were tapered on one end and had oval to pyriform swellings of 7-10 μm on the other, resulting in a bulbous appearance. Fungal elements stained positively with Gomori methenamine silver and Periodic acid-Schiff stains. The dog was euthanized at the owner's request, and necropsy revealed marked peripheral and visceral lymphadenomegaly. Histopathologic examination of lymph nodes confirmed granulomatous lymphadenitis with many fungal hyphae. Fungal culture yielded pure cultures of organisms that failed to produce ascospores or conidia precluding morphologic identification. PCR was performed using pan-fungal primers, ITS-1 and ITS-2, to amplify the intergenic spacer regions of ribosomal RNA; the PCR product was sequenced and a BLAST search of the GenBank databases at NCBI revealed 100% identity of the organism with Talaromyces helicus, the sexual form of Penicillium helicum. Talaromyces helicus has not previously been reported to cause disease in people or animals.     

Primary cardiac fibrosarcoma with pulmonary metastasis in a Labrador Retriever

A 6-year-old, neutered male Labrador Retriever was diagnosed with congestive heart failure, and an echocardiogram revealed a large mass inside the pericardial sac associated with the left ventricle. At necropsy, the dog had marked ascites, mild hydrothorax, marked hydropericardium, and an 11.0 x 7.0 x 6.0 cm, tan and red, firm, well-demarcated mass attached to the left ventricular free wall. The mass was diagnosed as a fibrosarcoma based on the morphologic appearance and supportive immunohistochemical staining. To our knowledge, this is the first case report of a primary fibrosarcoma involving the left ventricular free wall myocardium, epicardium, and pericardium with a pulmonary metastasis in a dog.     

Salmonella dublin Septicemia in Two Puppies

Two eight week old purebred female Bull Terrier puppies died within 24 hours of each other as a result of a septicemia caused by Salmonella dublin. The salient clinical features were: temperature of 41°C; rapid breathing; fluid, blood-stained stools; prostration and death. Pathological findings included embolic pneumonia, splenitis, myocarditis, nephritis and meningoencephalitis. Salmonella dublin was isolated from the spleen, lung and kidneys of both puppies.     

Iatrogenic,sulfonamide‐induced hypothyroid crisis in a Labrador Retriever

This case report describes a sulfonamide‐induced hypothyroid crisis in a 4‐year‐old Labrador Retriever bitch. Empirical therapy with high‐dose trimethoprim‐sulfamethoxazole for 10 days produced signs of weakness, ataxia and mental depression and the clinicopathological results supported hypothyroid‐induced central nervous system depression. Short‐term levothyroxine sodium therapy led to complete resolution of all clinical signs and follow‐up thyroid hormone assays ruled out underlying thyroid pathology. This case report is the first to highlight this potentially life‐threatening manifestation of sulfonamide‐induced hypothyroidism. Sulfonamide combinations are widely used antimicrobials in veterinary medicine and early recognition of this syndrome is critical.