Mevalonic acidemia: First case of Japan

Summary Mevalonic acidemia is a rare metabolic disorder due to mevalonate kinase deficiency which affects the biosynthesis of cholesterol and nonsterol isoprenes. We report the first case of Japan. The clinical course is characterized by intrauterine growth retardation, postnatal growth failure, intractable diarrhea, liver dysfunctions and death at three months of age. Dysmorphic features including triangular face, protrusion of forehead, hypertelorism, low set ears and micrognathism were noted. High mevalonic acid level was found by GC/MS.     

菏泽地区新生儿甲基丙二酸血症的 筛查及基因突变分析

目的 分析甲基丙二酸血症(MMA)患儿的临床表型、基因突变类型以及不同类型治疗效果,为该病的产前诊断提供科学依据。方法 利用串联质谱技术对菏泽市2015年5月-2019年12月出生的210 319名新生儿进行筛查,结合尿气相色谱质谱检测及二代测序技术,将确诊的88例患儿分为单纯型MMA患儿和MMA合并同型半胱氨酸血症,进行相应治疗,并采用配对样本t检验对患儿治疗前后进行比较分析。结果 88例MMA患儿中79例为MMA合并同型半胱氨酸血症,9例为单纯型MMA,49例患儿行基因测序,其中MUT基因突变位点13个,包括3个未报道突变:c.389G>A:1963C>T、c.2009G>T、c.1233_1235delCAT;MMACHA基因突变位点20个,包括5个未报道突变:c.481C>T、c.568dupT、c.57delT、c.471G>A、c.IVS2+149C>T。78例MMA合并同型半胱氨酸血症患儿治疗后较治疗前血中丙酰肉碱(C3)值和尿中甲基丙二酸值显著下降,差异有统计学意义(P<0.05)。结论 新生儿遗传代谢病筛查能对MMA早发现、早诊断、早治疗,并降低其死亡率和致残率。基因检测有助于MMA分型诊治,不同基因型的临床表型以及对治疗反应不同。新发突变位点,不仅丰富了我国MMA患儿基因突变谱,而且为先证者家系提供产前诊断。     

Long-term clinical outcomes of cochlear implantation in children with symptomatic epilepsy

ObjectivesTo describe long-term clinical outcomes of cochlear implantation in deaf children with symptomatic epilepsy.Materials and methodsA retrospective data analysis review of patients implanted at the Cochlear Implant Center of the University of Parma, Italy, was performed, searching for implanted children with a confirmed diagnosis of symptomatic epilepsy. Clinical data, imaging findings, pre- and post-operative epilepsy pattern and EEG traces were analyzed; communicative skills were assessed using the Profile of Actual Linguistic Skills.ResultsSearch retrieved two patients affected by profound bilateral sensorineural hearing loss and symptomatic epilepsy (associated respectively with methylmalonic acidemia and cerebral palsy). After careful parental counselling both patients were offered and underwent cochlear implantation. Activation and use of cochlear implant did not determine substantial changes of pre-existing seizure pattern and EEG traces. Both patients showed substantial development of their communicative abilities.ConclusionsCochlear implantation in children with symptomatic epilepsy did not determine variations in seizure pattern or EEG traces. Both patients experienced substantial benefit from cochlear implantation.     

Methylmalonic acidemia mimicking diabetic ketoacidosis and septic shock in infants

Methylmalonic acidemia (MMA) is most common inherited type of organic acidemia. It has diverse presentation in older infants without any initial apparent symptoms. MMA sometimes present with sudden metabolic decompensation, which may mimics common emergencies like septic shock and diabetic ketoacidosis (DKA) without early recognition can be fatal. In born error of metabolism especially organic acidemia should be suspected in any infant presented with severe high anion gap metabolic acidosis. We report two cases of MMA in infants presented acutely mimicking DKA and septic shock.     

Reversal of cardiomyopathy in propionic acidemia after liver transplantation: a 10‐year follow‐up

Cardiomyopathy is a frequent complication in propionic acidemia. It is mostly rapidly fatal and independent of the metabolic control or medical intervention. Here, we present the reversal of a severe cardiomyopathy after liver transplantation in a patient with propionic acidemia and the long‐term stability after ten years. Liver transplantation in patients with propionic acidemia may be considered a valid and long‐lasting treatment when cardiomyopathy is progressive and unresponsive to medical therapy.     

因预防接种诱发急性脑病的甲基丙二酸尿症cblA型一例

目的 报道1例因预防接种诱发急性脑病的中国甲基丙二酸尿症的cblA型病例.方法 就病例临床、血液酯酰肉碱谱、尿有机酸、甲基丙二酸尿症相关基因等特点进行分析.结果 患儿男,1岁3个月时因“间断呕吐、酸中毒、发育落后8个月”就诊.患儿生后7个月内发育正常,7个月时接种乙肝疫苗后lh出现呕吐、昏迷.临床诊断“中度脱水,电解质紊乱,代谢性酸中毒”,经补液等治疗后好转.此后,患儿发育落后,间断呕吐.1岁3个月时接种百白破疫苗,接种3h后再次出现呕吐,嗜睡,静脉补液后未见好转,7d后喘憋、呼吸困难、昏迷.患儿血液丙酰肉碱16.3μmol/L(参考值1.0 ～ 5.0μmol/L)、丙酰肉碱/游离肉碱0.27(参考值0.03 ～0.25)增高,尿甲基丙二酸(388.21 mmol/mol肌酐,参考值0.2～3.6 mmol/mol肌酐)及其代谢产物浓度显著增高,血浆总同型半胱氨酸浓度正常,符合单纯型甲基丙二酸血症,MMAA基因存在c.650 T＞A(p.L217X)和c.742 C＞T(p.Q248X)复合杂合突变,确诊为cblA型.经羟钴铵肌内注射、左卡尼汀、低蛋白饮食及特殊配方奶粉治疗后,患儿病情逐渐好转.患儿现2岁7个月,智力运动正常.结论 报道我国首例因预防接种诱发急性脑病的cblA型甲基丙二酸尿症.对疑似遗传代谢病患儿,预防接种前的代谢筛查是减少意外的关键.     

二甲双胍对2型糖尿病患者维生素B12、甲基丙二酸水平和神经病变的影响

目的 探讨二甲双胍对2型糖尿病患者维生素B12（Vit B₁₂）、甲基丙二酸（MMA）水平和神经病变的影响。方法 纳入2型糖尿病患者60例,按治疗方法分为观察组30例,对照组30例。两组均按入组前的剂量继续使用胰岛素治疗,此外,观察组给予二甲双胍治疗,对照组给予安慰剂治疗。两组疗程均为3年,通过定期门诊对患者进行随访,比较两组治疗前后空腹血糖（FPG）、餐后2 h血糖（PPPG）、糖化血红蛋白（HbA1c）、Vit B₁₂、MMA和神经病变评分的变化。结果 两组治疗后FPG、PPPG、HbA1c均显著下降,同组治疗前后比较差异有统计学意义（P<0.05）,且观察组显著低于对照组,组间差异有统计学意义（P<0.05）。两组治疗后肾小球滤过率（eGFR）均下降,同组治疗前后比较差异有统计学意义（P<0.05）;但组间无显著差异。治疗后,两组MMA均显著上升,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组更明显,组间差异有统计学意义（P<0.05）;VitB₁₂均显著下降,且观察组更明显（P<0.05）;两组神经病变评分有所上升,但组间无显著差异。结论 二甲双胍不仅会降低血浆VitB₁₂水平,还导致血浆MMA显著增加,血浆MMA增加与神经病变评分相关,提示临床应用二甲双胍时应监测Vit B₁₂。