Canine GM2‐Gangliosidosis Sandhoff Disease Associated with a 3‐Base Pair Deletion in the HEXB Gene

Background

GM2‐gangliosidosis is a fatal neurodegenerative lysosomal storage disease (LSD) caused by deficiency of either β‐hexosaminidase A (Hex‐A) and β‐hexosaminidase B (Hex‐B) together, or the GM2 activator protein. Clinical signs can be variable and are not pathognomonic for the specific, causal deficiency.

Objectives

To characterize the phenotype and genotype of GM2‐gangliosidosis disease in an affected dog.

Animals

One affected Shiba Inu and a clinically healthy dog.

Methods

Clinical and neurologic evaluation, brain magnetic resonance imaging (MRI), assays of lysosomal enzyme activities, and sequencing of all coding regions of HEXA, HEXB, and GM2A genes.

Results

A 14‐month‐old, female Shiba Inu presented with clinical signs resembling GM2‐gangliosidosis in humans and GM1‐gangliosidosis in the Shiba Inu. Magnetic resonance imaging (MRI) of the dog's brain indicated neurodegenerative disease, and evaluation of cerebrospinal fluid (CSF) identified storage granules in leukocytes. Lysosomal enzyme assays of plasma and leukocytes showed deficiencies of Hex‐A and Hex‐B activities in both tissues. Genetic analysis identified a homozygous, 3‐base pair deletion in the HEXB gene (c.618‐620delCCT).

Conclusions and Clinical Importance

Clinical, biochemical, and molecular features are characterized in a Shiba Inu with GM2‐gangliosidosis. The deletion of 3 adjacent base pairs in HEXB predicts the loss of a leucine residue at amino acid position 207 (p.Leu207del) supporting the hypothesis that GM2‐gangliosidosis seen in this dog is the Sandhoff type. Because GM1‐gangliosidosis also exists in this breed with almost identical clinical signs, genetic testing for both GM1‐ and GM2‐gangliosidosis should be considered to make a definitive diagnosis.     

Endogenous lipid pneumonia in cats: 24 cases (1985-1998)

OBJECTIVE: To determine clinical signs, radiographic and histologic abnormalities, and concurrent diseases in cats with endogenous lipid pneumonia (EnLP) and to determine the pathologic importance of EnLP in cats. DESIGN: Retrospective study. ANIMALS: 24 cats. PROCEDURE: Medical records of cats in which EnLP was confirmed by histologic examination of necropsy specimens were reviewed. Information collected from the medical records included signalment, body weight, clinical signs, and results of clinicopathologic tests. Thoracic radiographs were reviewed by a radiologist; histologic specimens were reviewed by a pathologist. RESULTS: All cats had nonspecific clinical abnormalities, such as lethargy, anorexia, or weight loss; 16 had signs of respiratory tract disease. All cats had concurrent systemic diseases, and clinicopathologic abnormalities were reflective of these conditions. Nonspecific abnormalities were detected on thoracic radiographs from 9 of 11 cats. Most cats had macroscopic, multifocal, subpleural lesions; inflammatory infiltrates, cholesterol clefts, and multinucleated giant cells were common. Ten cats had an underlying obstructive pulmonary disease that was the likely cause of EnLP. Lesions of EnLP were not considered to be severe enough or extensive enough to be the cause of death in any of these cats. CONCLUSIONS AND CLINICAL RELEVANCE: EnLP is an uncommon respiratory tract disorder of cats with no pathognomonic clinical, laboratory, or radiographic findings. Although EnLP was not the cause of death in any of these cats, results of the present study do suggest that EnLP may be a marker for potentially severe underlying obstructive pulmonary disease.     

Pulmonary Thromboembolism in 29 Dogs: 1985–1995

Pulmonary thromboembolism (PTE) occurs as a complication to a number of commonly encountered clinical diseases. Antemortem recognition of this life-threatening disorder is hampered by nonspecificity of clinical signs. This retrospective study was performed to analyze clinical features, laboratory findings, imaging abnormalities, and concurrent postmortem diagnoses in 29 dogs with confirmed pulmonary embolism. A variety of clinicopathologic and radiographic abnormalities were noted but there were no pathognomonic findings for PTE. Arterial blood gas analyses were performed in 15 (52%) of 29 dogs; 12 (80%) of 15 exhibited hypoxemia and 15 (100%) of 15 had increased alveolar-arterial oxygen gradients. Response to supplemental O2 was variable and did not correlate with the presence or absence of additional pulmonary pathology on postmortem. At postmortem, 25 (86%) of 29 dogs had grossly visible emboli, 17 (59%) of 29 dogs had multiple disease processes, and 16 (55%) of 29 dogs had additional pulmonary pathology. PTE was suspected antemortem in 11 (38%) of 29 dogs. In dogs with respiratory signs consistent with PTE, the condition was a differential diagnosis in 11 of 17 animals; all had diseases previously reported to be associated with PTE. Neoplasia, systemic bacterial disease, and immune-mediated hemolytic anemia were diagnosed most frequently.     

Clinical and molecular analysis of GM2 gangliosidosis in two apparent littermate kittens of the Japanese domestic cat

This case report documents clinical and molecular findings in two littermate kittens of the Japanese domestic cat with GM2 gangliosidosis variant 0. Analysis included detailed physical, magnetic resonance imaging, biochemical, pathological and genetic examinations. At first, these littermate kittens showed typical cerebellar signs at approximately 2 months of age. About 2 months later, they progressively showed other neurological signs and subsequently died at about 7 months of age. Magnetic resonance imaging just before the death showed an enlarged ventricular system, T1 hyperintensity in the internal capsule, and T2 hyperintensity in the white matter of the whole brain. Histological findings suggested a type of lysosomal storage disease. Biochemical studies demonstrated that the kittens were affected with GM2 gangliosidosis variant 0, and a DNA assay finally demonstrated that these animals were homozygous for the mutation, which the authors had identified in a different family of the Japanese domestic cat. The findings in the present cases provide useful information about GM2 gangliosidosis variant 0 in Japanese domestic cats.     

Clinical differentiation of acute necrotizing from chronic nonsuppurative pancreatitis in cats: 63 cases (1996-2001)

OBJECTIVE: To characterize clinical, clinicopathologic, radiographic, and ultrasonographic findings in cats with histologically confirmed acute necrotizing pancreatitis (ANP) or chronic nonsuppurative pancreatitis (CP) and identify features that may be useful in the antemortem differentiation of these disorders. DESIGN: Retrospective study. ANIMALS: 63 cats with histologically confirmed ANP (n = 30) or CP (33). PROCEDURE: Medical records were reviewed for signalment, clinical signs, concurrent diseases, clinicopathologic findings, and results of radiography and ultrasonography. RESULTS: Cats in both groups had similar nonspecific clinical signs, physical examination findings, and radiographic and ultrasonographic abnormalities. Abdominal ultrasonographic abnormalities, including hypoechoic pancreas, hyperechoic mesentery, and abdominal effusion, were found in cats in both groups and, therefore, were not specific for ANP. Cats with CP were significantly more likely to have concurrent diseases than were cats with ANP (100 and 83%, respectively). Clinicopathologic abnormalities were similar between groups; however, serum alanine aminotransferase and alkaline phosphatase activities were significantly higher in cats with CP. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that ANP and CP in cats cannot be distinguished from each other solely on the basis of history, physical examination findings, results of clinicopathologic testing, radiographic abnormalities, or ultrasonographic abnormalities.     

Familial glomerulonephropathy in the Bullmastiff

Glomerular disease was diagnosed by histopathologic examination in 11 related Bullmastiff dogs, and clinical and laboratory data were collected retrospectively. Four female and seven male dogs between the ages of 2.5 and 11 years were affected. Clinical signs, including lethargy and anorexia, were nonspecific and occurred shortly before death or euthanasia. In five affected dogs serial blood samples were obtained, and dramatically elevated blood urea nitrogen and creatinine levels were demonstrated up to 2.75 years before death. Protein-creatinine ratios were elevated in six of six dogs and were above normal 3.5 years before death in one dog. The kidneys appeared grossly normal to slightly smaller than normal at necropsy. Histologic abnormalities of the kidneys were consistent with chronic glomerulonephropathy with sclerosis. Examination of the pedigrees of related affected dogs yielded evidence supporting an autosomal recessive mode of inheritance.     

Pathology of GM2 gangliosidosis in Jacob sheep

The G(M2) gangliosidoses are a group of lysosomal storage diseases caused by defects in the genes coding for the enzyme hexosaminidase or the G(M2) activator protein. Four Jacob sheep from the same farm were examined over a 3-year period for a progressive neurologic disease. Two lambs were 6-month-old intact males and 2 were 8-month-old females. Clinical findings included ataxia in all 4 limbs, proprioceptive deficits, and cortical blindness. At necropsy, the nervous system appeared grossly normal. Histologically, most neurons within the brain, spinal cord, and peripheral ganglia were enlarged, and the cytoplasm was distended by foamy to granular material that stained positively with Luxol fast blue and Sudan black B stains. Other neuropathologic findings included widespread astrocytosis, microgliosis, and scattered spheroids. Electron microscopy revealed membranous cytoplasmic bodies within the cytoplasm of neurons. Biochemical and molecular genetic studies confirmed the diagnosis of G(M2) gangliosidosis. This form of G(M2) gangliosidosis in Jacob sheep is very similar to human Tay-Sachs disease and is potentially a useful animal model.     

Liver lobe torsion in dogs: 13 cases (1995-2004)

OBJECTIVE: To determine history, results of diagnostic testing, surgical findings, complications, and outcome for dogs with liver lobe torsion (LLT). DESIGN: Retrospective case series. ANIMALS: 12 dogs (1 with 2 episodes). PROCEDURE: Signalment, clinical signs, clinicopathologic findings, radiographic and ultrasonographic findings, surgical and histologic findings, complications, and hospitalization time were evaluated. RESULTS: The most common clinical signs were nonspecific abnormalities (eg, vomiting, lethargy, and anorexia) of acute or chronic duration. All dogs were large-breed dogs (median body weight, 37.2 kg [82 lb]). Biochemical abnormalities included high alanine amino-transferase (n = 12) and aspartate aminotransferase (11) activities. Results of abdominal ultrasonography were supportive of the diagnosis in 5 of 8 cases. Affected lobes included the left medial lobe (n = 4), left lateral lobe (3), papillary process of the caudate lobe (2), caudate lobe (1), and right lateral lobe (1). Exploratory celiotomy and liver lobectomy were performed in 12 of 13 cases, and in 11 of those 12 cases, the dog survived. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that development of nonspecific clinical signs of vomiting, lethargy, and anorexia in conjunction with high serum hepatic enzyme activities and mature neutrophilia in a medium-sized or large-breed dog should increase the index of suspicion for LLT. Abdominal ultrasonography with Doppler assessment may be useful in establishing the diagnosis. The long-term outcome for dogs that survive the hospitalization period is excellent.     

Risk factors associated with outcome in dogs with tetanus: 38 cases (1987-2005)

OBJECTIVE: To assess the clinical course of disease and risk factors associated with outcome in dogs with tetanus. DESIGN: Retrospective case series. ANIMALS: 38 dogs with tetanus. PROCEDURES: Data were collected from medical records of dogs with tetanus, including signalment; wound characteristics; initial clinical signs; severity of worst clinical signs; time to wound management, antimicrobial treatment, and antitoxin administration; and 28-day survival rate. Statistical analyses were performed to evaluate relationships between the potentially predictive variables and disease progression and outcome. RESULTS: The 28-day survival rate was 77% (among 35 uncensored dogs). The most common initial clinical signs in affected dogs were ocular (n = 18) and facial (11) abnormalities. Nineteen dogs progressed to recumbency with severe muscle spasms, and 14 dogs had high or low heart rate or blood pressure values. Eight dogs died or were euthanized because of complications of tetanus. There was a significant association between younger age and development of more severe clinical signs. Furthermore, a significant inverse relationship between development of severe clinical signs and survival was identified. There was no association between earlier initiation of wound management, antimicrobial administration, or antitoxin administration and either progression of signs or 28-day survival rate. Wound type was not associated with 28-day survival rate. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that younger dogs with tetanus may be more likely to develop severe clinical signs. The prognosis for survival in dogs with tetanus is good if abnormalities in heart rate or blood pressure values do not develop.     

Measurement of serum antinuclear antibody titer in dogs with and without systemic lupus erythematosus: 120 cases (1997-2005)

OBJECTIVE: To determine serum antinuclear antibody (ANA) titers in dogs with systemic lupus erythematosus (SLE) and in dogs with related clinical and clinicopathologic findings. DESIGN: Retrospective case series. ANIMALS: 120 dogs. PROCEDURES: Information that was evaluated included signalment, clinical signs, results of routine laboratory testing, ANA titer, and diagnosis. RESULTS: The most common clinical signs were arthralgia, myalgia, and stiffness (n = 41 [34.2%]); the most common clinicopathologic abnormality was thrombocytopenia (30 [25%]). Serum ANA titer was < 160 (seronegative) in 89 dogs (74.2%), 160 in 14 dogs (11.7%), 320 in 5 dogs (4.2%), and > or = 640 in 12 dogs (10%). Immune-mediated disease was confirmed in 40 dogs, 18 of which fulfilled the criteria for a definitive or probable diagnosis of SLE. Only 1 of 47 dogs with no major signs compatible with SLE had immune-mediated disease, compared with 26 of 57 dogs with 1 major sign and 13 of 16 dogs with > or = 2 major signs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that measurement of ANA titer was not a useful diagnostic test in dogs without any major clinical or clinicopathologic abnormalities suggestive of SLE. In contrast, there was a good chance that results of the ANA assay would be positive and that the dog would be found to have immune-mediated disease if at least 2 major signs were evident. Findings suggest that it would be reasonable to limit the use of the ANA assay to those dogs that have at least 1 major sign compatible with a diagnosis of SLE.     

Putative uremic encephalopathy in horses: five cases (1978-1998)

OBJECTIVE: To determine historical, physical examination, clinicopathologic, and postmortem findings in horses with putative uremic encephalopathy. Design-Retrospective study. Animals-5 horses with renal failure and neurologic disease not attributable to abnormalities in any other organ system. PROCEDURE: Medical records from 1978 to 1998 were examined for horses with renal disease and neurologic signs not attributable to primary neurologic, hepatic, or other diseases. Signalment, history, physical examination findings, clinicopathologic data, renal ultrasonographic findings, and postmortem data were reviewed. RESULTS: Of 332 horses with renal disease, 5 met selection criteria. Historical findings, physical examination findings, clinicopathologic data, ultrasonographic data, and postmortem findings were consistent with chronic renal failure. Swollen astrocytes were detected in all 4 horses examined at necropsy. CONCLUSIONS AND CLINICAL RELEVANCE: A single criterion was not determined to be pathognomonic for uremic encephalopathy in horses. Uremic encephalopathy should be considered as a differential diagnosis in horses with evidence of chronic renal failure and encephalopathic neurologic sign not attributable to other causes. Astrocyte swelling, which was common to all 4 horses examined at necropsy, may serve as a microscopic indicator of uremic encephalopathy in horses.     

Neuronal-Visceral GM1 Gangliosidosis in Portuguese Water Dogs

Three female siblings in a litter of seven Portuguese Water dogs (PWDs) showed clinical signs of ataxia and/or lameness at 5 months of age. Signs of cerebellar dysfunction (intention tremors, ataxia, widebased stance, dysmetria, and/or nystagmus) and mild limb weakness developed rapidly. Results of hemograms (three dogs), blood chemistry profiles (two dogs), urinalyses (two dogs), electroencephalograms (two dogs), and radiographs of the limbs or pelvis (three dogs), vertebrae (two dogs), and skull (one dog) were unremarkable except for an absolute lymphocytosis in one dog. Routine cerebrospinal fluid (CSF) analyses were normal in all three dogs. However, the CSF creatine kinase concentration was elevated in the one dog in which it was measured. Mucopolysacchariduria was present in all three dogs. Due to the rapid progression of clinical signs and a poor prognosis, all three dogs were euthanatized between 6 and 7 months of age. Histopathologic and electron microscopic studies showed neuronal cytoplasmic inclusions, vacuolated hepatocytes, and vacuolated renal tubular epithelial cells, compatible with the diagnosis of a storage disease. Beta-galactosidase activities in leukocytes, serum, and brain homogenates were reduced when compared with that in normal dogs and the stored product was identified as GM1 ganglioside, confirming GM1 gangliosidosis.     

Tryptamine alkaloid toxicosis in feedlot sheep

Tryptamine alkaloid toxicosis (Phalaris staggers) was diagnosed in feedlot sheep. Clinical signs of toxicosis, which were exacerbated by excitement, included gait abnormalities, muscular tremors, nystagmus, and convulsions. An estimated 8% of the most severely affected lambs had clinical signs of toxicosis. Gross lesions detected in the brain of affected lambs consisted of focal gray-green discoloration in the brain stem and thalamus; these areas had microscopic evidence of intraneuronal pigment accumulation. Brain specimens obtained at slaughter indicated that 60% of the lambs had lesions consistent with tryptamine alkaloid toxicosis. Tryptamine alkaloids were found in low concentrations in the feed. Lambs exposed to these feeds had higher death losses than those that were not exposed to the feeds. Cobalt concentration in the feed was higher than that previously reported to be associated with Phalaris staggers.     

Clinical, clinicopathologic, pathologic, and toxicologic alterations associated with gossypol toxicosis in feeder lambs

The toxicity of gossypol was studied in 20, 8-week-old feeder lambs that weighed approximately 16 kg. The lambs were allotted to 4 groups (A, B, C, D) and given (orally for 30 days) a daily dosage of gossypol (0, 45, 136, or 409 mg, respectively). Lambs were observed twice daily until they died or were euthanatized on the day the last dose was given. Clinical, electrocardiographic, clinicopathologic, pathologic, and toxicologic findings were recorded. All lambs given 409 mg of gossypol (group D) died before the end of the 30-day study. In this group, clinical signs included sudden death and/or chronic dyspnea syndromes. One group-B lamb had chronic dyspnea, but did not die. Electrocardiographic abnormalities observed in gossypol-treated lambs included increased amplitude of the T wave and decreased duration of the ST segment. Clinicopathologic alterations in group-D lambs included high serum total lactate dehydrogenase and lactate dehydrogenase liver-specific isoenzyme activities. Serum total creatine kinase activity decreased markedly in lambs of all groups treated with gossypol. Hemoglobinuria was detected in 2 group-D lambs. The average daily weight gain was remarkably consistent in lambs of all groups, except in 1 lamb each of groups D and B. Lambs were necropsied when they died or on day 30 of the study. The heart of gossypol-treated lambs weighted more than did that of untreated (control group A) lambs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Water deprivation-sodium chloride intoxication in a group of feeder lambs

Six of a group of 100 feeder lambs that had been deprived of sodium chloride, then more recently deprived of water, developed water deprivation-sodium chloride intoxication soon after water and a mineral supplement containing sodium chloride were reintroduced. The clinical signs included somnolence, intense thirst, and generalized muscle fasciculations. Serum chemical analyses revealed profound hypernatremia and hyperchloremia. Two mildly affected lambs recovered with partial water restriction and 2 severely affected lambs died despite medication to reduce cerebral edema. Postmortem examination of the 2 treated lambs and the 2 lambs found dead revealed microscopic evidence of cerebral edema and cerebrocorticonecrosis.     

GM2 Gangliosidosis in Shiba Inu Dogs with an In‐Frame Deletion in HEXB

Consistent with a tentative diagnosis of neuronal ceroid lipofuscinosis (NCL), autofluorescent cytoplasmic storage bodies were found in neurons from the brains of 2 related Shiba Inu dogs with a young‐adult onset, progressive neurodegenerative disease. Unexpectedly, no potentially causal NCL‐related variants were identified in a whole‐genome sequence generated with DNA from 1 of the affected dogs. Instead, the whole‐genome sequence contained a homozygous 3 base pair (bp) deletion in a coding region of HEXB. The other affected dog also was homozygous for this 3‐bp deletion. Mutations in the human HEXB ortholog cause Sandhoff disease, a type of GM2 gangliosidosis. Thin‐layer chromatography confirmed that GM2 ganglioside had accumulated in an affected Shiba Inu brain. Enzymatic analysis confirmed that the GM2 gangliosidosis resulted from a deficiency in the HEXB encoded protein and not from a deficiency in products from HEXA or GM2A, which are known alternative causes of GM2 gangliosidosis. We conclude that the homozygous 3‐bp deletion in HEXB is the likely cause of the Shiba Inu neurodegenerative disease and that whole‐genome sequencing can lead to the early identification of potentially disease‐causing DNA variants thereby refocusing subsequent diagnostic analyses toward confirming or refuting candidate variant causality.     

Intestinal neoplasia in horses

BACKGROUND: Intestinal neoplasia of horses is inadequately described. HYPOTHESIS: Intestinal neoplasia of horses has characteristic clinicopathologic features. ANIMALS: Thirty-four horses with intestinal neoplasia. METHODS: Retrospective study. RESULTS: Anamnesis, clinical signs, clinicopathologic and pathologic findings in 34 adult horses diagnosed histologically with intestinal neoplasia were reviewed. The horses ranged in age from 2 to 30 years (mean 16.6 years at presentation). The Arabian breed was most represented and there was no sex predisposition. The most common presenting complaints were weight loss, colic, anorexia, and fever. The most consistent clinical signs were poor body condition, tachycardia, tachypnea, fever, and diarrhea. Useful diagnostic tools included rectal examination, routine blood analyses, abdominocentesis, ultrasonographic examination, rectal biopsy, and exploratory laparotomy. Alimentary lymphoma was the most common intestinal neoplasia identified, followed by adenocarcinoma and smooth muscle tumors. The small intestine was the most common segment of intestine affected for all neoplasms. Intestinal neoplasia was diagnosed antemortem in 13 of 34 (38%) horses. The median time from onset of clinical signs to death or euthanasia was 1.9 months. The discharge rate was 15%. Although the longest survival was observed in horses with jejunal adenocarcinoma, all horses were eventually euthanized because of intestinal neoplasia. CONCLUSIONS: Arabian horses were 4.5 times more likely to have intestinal neoplasia diagnosed than were other breeds.     

Clinical, clinicopathologic, radiographic, and ultrasonographic abnormalities in cats with ureteral calculi: 163 cases (1984-2002)

OBJECTIVE: To determine clinical, clinicopathologic, radiographic, and ultrasonographic abnormalities in cats with ureteral calculi. DESIGN: Retrospective study. ANIMALS: 163 client-owned cats. PROCEDURE: Medical records were reviewed, and information on signalment, history, clinical signs, and results of clinicopathologic testing and diagnostic imaging was obtained. RESULTS: The number of cats in which ureterolithiasis was diagnosed each year increased progressively during the study period. Clinical signs tended to be non-specific and included inappetence, vomiting, lethargy, and weight loss. A combination of survey radiography and abdominal ultrasonography revealed ureteral calculi in 66 of 73 (90%) cats in which the diagnosis was confirmed at surgery or necropsy. Ultrasonography revealed that ureteral calculi were causing ureteral obstruction in 143 of 155 (92%) cats. One hundred thirty-four of 162 (83%) cats had azotemia, 84 of 156 (54%) had hyperphosphatemia, and 22 of 152 (14%) had hypercalcemia. Urinary tract infection was documented in 10 of 119 (8%). Fifty-eight of 76 (76%) cats with unilateral ureterolithiasis had azotemia and 33 (43%) had hyperphosphatemia, indicating impairment of renal function in the contralateral kidney or prerenal azotemia. Ultrasonographic imaging of the contralateral kidney in cats with unilateral ureteral calculi suggested that preexisting renal parenchymal disease was common in cats with ureterolithiasis. Ninety-one of 93 (98%) ureteral calculi contained calcium oxalate. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that abdominal imaging should be performed in all cats with chronic nonspecific signs or with acute or chronic renal failure to rule out ureterolithiasis. Preexisting renal disease may be common in cats with ureteral calculi.     

Biochemical and haematological evidence of endotoxic shock in gnotobiotic lambs with watery mouth disease

Eight gnotobiotic lambs deprived of colostrum were infected by mouth when two hours old with nonenterotoxigenic strains of Escherichia coli. All developed clinical signs of watery mouth disease and seven died within 24 hours. The mean concentrations of several blood constituents were determined in samples taken at intervals until 24 hours after infection in infected lambs and in four control lambs. The biochemical and haematological changes observed in the lambs developing watery mouth disease were those characteristic of endotoxic shock.     

Epidermolysis bullosa in German black headed mutton sheep

In three flocks, 13 pure- and 1 crossbred German black headed mutton lambs were ascertained which had clinical signs of epidermolysis bullosa (EB). The three farmers reported of further 20 affected lambs with similar signs in their flocks in the past lambing seasons. The affected lambs were progeny of six rams and 17 ewes. Two rams and six ewes with affected offspring from two farms were used for a breeding trial. In the course of these experimental matings, 21 lambs were born, six of which were affected by EB. All lambs born in this trial underwent clinical and haematological examination and all the affected lambs had to be euthanised due to severe and progressing clinical symptoms. Clinical examinations in 20 affected lambs revealed shedding of claw horn, erosions and ulcers of skin and mucous membranes. Histopathology showed subepidermal splitting and blistering with intact basal keratinocytes. These findings together with the premature death of affected lambs within the first two months of life made a Herlitz type of junctional EB most likely. The results of the test matings demonstrated the genetic transmission and indicated an autosomal recessive mode of inheritance for this lethal condition.