Four female Shetland Sheepdogs with hypertonic paroxysmal dyskinesia, mainly triggered by exercise and stress, were investigated in a retrospective multi-center investigation aiming to characterize the clinical phenotype and its underlying molecular etiology. Three dogs were closely related and their pedigree suggested autosomal dominant inheritance. Laboratory diagnostic findings included mild lactic acidosis and lactaturia, mild intermittent serum creatine kinase (CK) elevation and hypoglycemia. Electrophysiological tests and magnetic resonance imaging of the brain were unremarkable. A muscle/nerve biopsy revealed a mild type II fiber predominant muscle atrophy. While treatment with phenobarbital, diazepam or levetiracetam did not alter the clinical course, treatment with a gluten-free, home-made fresh meat diet in three dogs or a tryptophan-rich, gluten-free, seafood-based diet, stress-reduction, and acetazolamide or zonisamide in the fourth dog correlated with a partial reduction in, or even a complete absence of, dystonic episodes. The genomes of two cases were sequenced and compared to 654 control genomes. The analysis revealed a case-specific missense variant, c.1658G>A or p.Arg553Gln, in the PCK2 gene encoding the mitochondrial phosphoenolpyruvate carboxykinase 2. Sanger sequencing confirmed that all four cases carried the mutant allele in a heterozygous state. The mutant allele was not found in 117 Shetland Sheepdog controls and more than 500 additionally genotyped dogs from various other breeds. The p.Arg553Gln substitution affects a highly conserved residue in close proximity to the GTP-binding site of PCK2. Taken together, we describe a new form of paroxysmal exercise-induced dyskinesia (PED) in dogs. The genetic findings suggest that PCK2:p.Arg553Gln should be further investigated as putative candidate causal variant.

Dietary phosphorus frequently exceeds age-specific requirements and pig manure often contains high phosphorus load which causes environmental burden at regional scales. Therefore, feeding strategies towards improved phosphorus efficiency and reduced environmental phosphorus load have to be developed. A 5-week feeding trial was conducted: piglets received medium, lower (−25%), or higher (+25%) amounts of phosphorus and calcium. Dietary responses were reflected by performance parameters, bone characteristics, and molecular data retrieved from serum, intestinal mucosa, and kidney cortex (p < 0.05). Transcripts associated with vitamin D hydroxylation (Cyp24A1, Cyp27A1, Cyp27B1) were regulated by diet at local tissue sites. Low-fed animals showed attempts to maintain mineral homoeostasis via intrinsic mechanisms, whereas the high-fed animals adapted at the expense of growth and development. Results suggest that a diet containing low phosphorus and calcium levels might be useful to improve resource efficiency and to reduce phosphorus losses along the agricultural value chain.

Sufficient supply of pigs with calcium (Ca) and phosphorus (P) is essential for animal health and welfare during the growth period. However, the P content in animal manure is considered as a cause of massive environmental problems in soil and aquatic ecosystems. To complement previous findings, the objective of this study is the investigation of effects of a reduced and increased Ca and P supplementation on bone mineralization and bone structure compared with the current dietary recommendation. Another aim is to find possible serum markers that would allow the assessment of adequacy of P supply for bone health during growth. The result validated that the recommended Ca and P supply is sufficient, without the addition of microbial phytases. However, addition of P has no further beneficial effects on bone stability, while P supplementation below the recommended level affects bone development and growth performance. Reduced P levels have consequences for cancellous bone density and trabecular architecture. Further fine‐tuning of the P supply in conjunction with an appropriate Ca supply will contribute to a reduction in P waste and associated environmental impact while maintaining animal health and welfare.

Purpose: New aspects like acetabular overcoverage, acetabular retroversion and proximal femoral head-neck dysplasia have been detected as a main cause of osteoarthritis. The study addresses the detection of reasons for osteoarthritis requiring THA in young adults. We wanted to prove the hypothesis that idiopathic reasons play an overestimated role in osteoarthritis in young patients. Materials and Methods: 228 total hip arthroplasties in patients aged ≤ 60 years were performed at our institution. After the detection of the primary reasons for osteoarthritis of the hip, the radiographic pictures of all other patients were analyzed for radiographic signs of hip dysplasia or femoroacetabular impingement. For interobserver quality testing, this was done by two different observers. Results: 132 patients were initially classified as having idiopathic osteoarthritis of the hip. There was no pathological radiographic finding in only 5 patients. 80 patients presented a reduced head-neck offset as a sign of CAM impingement with a mean head ratio of 1.52 ± 0.35 and an alpha angle of 62.8 ± 9.28°. 21 patients presented a figure-8 sign as an indicator for acetabular retroversion. 68 patients presented at least one radiographic finding for “dysplasia” and 60 patients at least one radiographic finding for excessive “overcoverage”. The Bland-Altman Plot for testing interobserver reliability demonstrated good interobserver agreement. Conclusion: Idiopathic OA in young adults is rare if you look hard enough for the underlying pathology. If treated, patients might benefit and THA could be postponed for several years. Ziel: Eine übermäßige Überdachung, acetabuläre Retroversion und Störungen im Übergangsbereich von Hüftkopf zum Schenkelhals werden als eine wesentliche Ursache für eine Hüftarthrose gesehen. Diese Arbeit setzt sich mit der Erkennung von Ursachen einer frühen Arthrose des Hüftgelenks auseinander. Es soll die Hypothese untersucht werden, dass idiopathische Ursachen eine untergeordnete Rolle spielen. Material und Methoden: 228 Hüftgelenkstotalendoprothesen wurden in Patienten implantiert, die zum Operationszeitpunkt jünger als 60 Jahre waren. Nachdem primäre Ursachen für eine Hüftgelenksarthrose ausgeschlossen wurden, wurden die radiologischen Bilder der restlichen Patienten auf Zeichen von Dysplasie und femoroacetabulärem Impingement untersucht. Um die Übereinstimmung zu bestimmen, wurde dies von zwei Auswertern vorgenommen. Ergebnisse: Bei 132 Patienten wurde initial die Diagnose einer idiopathischen Arthrose des Hüftgelenks gestellt. Nur in 5 Fällen waren die radiologischen Bilder unauffällig. 80 Patienten hatten ein vermindertes Head-Neck Offset als Zeichen für ein CAM-Impingement mit einer durchschnittlichen Head-Ratio von 1,52 ± 0,35 und einem Alpha-Winkel von 62,8 ± 9,28°. 21 Patienten zeigten ein Figure-8-Sign als Hinweis für eine acetabuläre Retroversion. 68 Patienten hatten zumindest ein radiologisches Zeichen als Hinweis auf „Hüftdysplasie“ und 60 Patienten zeigten Zeichen für eine übermäßige Überdachung des Hüftkopfs. Mithilfe des Bland-Altman-Plots konnte eine gute Übereinstimmung zwischen den beiden Auswertern nachgewiesen werden. Schlussfolgerung: Idiopathische Arthrose spielt in jungen Erwachsenen nur eine untergeordnete Rolle, wenn man genau auf die zugrunde liegende Pathologie achtet. Falls diese Patienten behandelt werden, könnte die Implantation einer Hüftgelenkstotalendoprothese um Jahre hinausgezögert werden.

Phosphorus (P) is an important element of various metabolic and signalling processes, including bone metabolism and immune function. To elucidate the routes of P homeostasis and utilization, a five-week feeding study was conducted with weaned piglets receiving a diet with recommended amounts of P and Ca (M), or a diet with lower (L) or higher (H) P values and a constant Ca:P ratio. Routes of P utilization were deduced via bone characteristics (MicroCT), genome-wide transcriptomic profiles of peripheral blood mononuclear cells (PBMCs), and serum mineral levels. MicroCT revealed significantly lower bone mineral density, trabecular number, and mechanical fracture load in (L). Gene expression analyses showed transcripts of 276 and 115 annotated genes with higher or lower abundance in (H) than (L) that were related to basic cellular and metabolic processes as well as response to stimuli, developmental processes and immune system processes. This study shows the many molecular routes involved in P homeostasis that should be considered to improve endogenous mechanisms of P utilization.

Sodium/phosphate co-transporters are considered to be important mediators of phosphorus (P) homeostasis. The expression of specific sodium/phosphate co-transporters is routinely used as an immediate response to dietary interventions in different species. However, a general understanding of their tissue-specificity is required to elucidate their particular contribution to P homeostasis. In this study, the tissue-wide gene expression status of all currently annotated sodium/phosphate co-transporters were investigated in two pig trials focusing on a standard commercial diet (trial 1) or divergent P-containing diets (trial 2). A wide range of tissues including the gastrointestinal tract (stomach, duodenum, jejunum, ileum, caecum, and colon), kidney, liver, bone, muscle, lung, and aorta were analyzed. Both trials showed consistent patterns in the overall tissue-specific expression of P transporters. While SLC34A2 was considered as the most important intestinal P transporter in other species including humans, SLC34A3 appeared to be the most prominent intestinal P transporter in pigs. In addition, the P transporters of the SLC17 family showed basal expression in the pig intestine and might have a contribution to P homeostasis. The expression patterns observed in the distal colon provide evidence that the large intestine may also be relevant for intestinal P absorption. A low dietary P supply induced higher expressions of SLC20A1, SLC20A2, SLC34A1, and SLC34A3 in the kidney cortex. The results suggest that the expression of genes encoding transcellular P transporters is tissue-specific and responsive to dietary P supply, while underlying regulatory mechanisms require further analyses.