West Natalie, Matiasek Kaspar, Rusbridge Clare
Fitzpatrick Referrals, Guildford, UK.
Section of Clinical and Comparative Neuropathology, Centre for Clinical Veterinary Medicine, LMU Munich, Munich, Germany.
JFMS Open Rep. 2021 Oct 6;7(2):20551169211037899. doi: 10.1177/20551169211037899. eCollection 2021 Jul-Dec.
A rescue charity-owned 6-month-old neutered female domestic shorthair cat was presented with progressive tetraparesis, increased extensor muscle tone and signs of spinocerebellar ataxia, including hypermetria. The cat's male sibling, with similar progressive neurological signs, had been euthanased 2 months previously. An inherited metabolic disorder was suspected. Urine for determination of organic acid concentration was obtained and the cat was prescribed carnitine and taurine supplementation. The cat was euthanased 3 months later following progressive neurological signs, including ataxia, tetraparesis, tendency to fall, bilateral absent menace response and intention tremor. A selective post-mortem examination was obtained, taking samples from the brain, cervical spinal cord, tibial branch of the sciatic nerve, muscle, liver and kidneys. Organic acid analysis results received after euthanasia revealed a marked elevation of 3-hydroxy-3-methylglutaric acid (45 mmol/mol creatine [normal range 0-2]) and isovalerylglycine (27 mmol/mol creatinine [normal range 0-2]). 3-Hydroxy-3-methylglutaric acid was deemed clinically relevant as it is a metabolite of 3-hydroxy-3-methylglutaryl-CoA lyase, the enzyme involved in the final step of leucine degradation. Post-mortem examination revealed diffuse, chronic-active, severe olivoponto-(spino)-cerebellar degeneration.
This is the first report of 3-hydroxy-3-methylglutaric aciduria in the veterinary literature and the first description of the neuropathology of this disorder in any species. 3-Hydroxy-3-methylglutaric aciduria in humans occurs rarely and is due to a deficiency in 3-hydroxy-3-methylglutaryl-coenzyme A lyase.
一只6个月大、已绝育的雌性家养短毛猫，归一家救援慈善机构所有，出现进行性四肢轻瘫、伸肌肌张力增加以及脊髓小脑性共济失调的症状，包括辨距不良。这只猫的雄性同胞有类似的进行性神经症状，已于2个月前实施安乐死。怀疑是遗传性代谢紊乱。采集尿液以测定有机酸浓度，并给这只猫开了补充肉碱和牛磺酸的药方。3个月后，这只猫因出现包括共济失调、四肢轻瘫、跌倒倾向、双侧威胁反应消失和意向性震颤在内的进行性神经症状而实施安乐死。进行了选择性尸检，从大脑、颈脊髓、坐骨神经胫支、肌肉、肝脏和肾脏采集样本。安乐死后收到的有机酸分析结果显示，3-羟基-3-甲基戊二酸（45 mmol/mol肌酸[正常范围0 - 2]）和异戊酰甘氨酸（27 mmol/mol肌酐[正常范围0 - 2]）显著升高。3-羟基-3-甲基戊二酸被认为具有临床相关性，因为它是3-羟基-3-甲基戊二酰辅酶A裂解酶的代谢产物，该酶参与亮氨酸降解的最后一步。尸检显示弥漫性、慢性活动性、严重的橄榄脑桥（脊髓）小脑变性。
这是兽医文献中关于3-羟基-3-甲基戊二酸尿症的首次报告，也是该疾病在任何物种中的神经病理学首次描述。人类的3-羟基-3-甲基戊二酸尿症很少见，是由于3-羟基-3-甲基戊二酰辅酶A裂解酶缺乏所致。
