Objective To explore the clinical characteristics of late-onset ornithine carbamoyltransferase deficiency (OTCD) in order to improve the clinicians' understanding of this disease.Methods The clinical,therapeutic and follow-up data of two patients with late-onset OTCD diagnosed in the Department of Neurology,Qilu Hospital of Shandong University from November 2017 to February 2018 were collected and analyzed.Results Case 1 is a 17-year-old male who was admitted into Qilu Hospital with recurrent dizziness and vomiting for 4 months,sudden mental abnormality and convulsion for 3 days.The liver dysfunction,respiratory alkalosis and hyperammonemia (434 μmol/L) had been found before his admission.His blood ammonia fluctuated obviously from 180 μ mol/L to 2998 μmol/L,though he was given hemodialysis and arginine infusion,and died on the fourth day after admission.Case 2 is a 15-year-old male,complained with recurrent dizziness,vomiting,bluntness and somnolence for 20 days.He was found with hyperammonemia (600 μmol/L) and liver dsyfunction in a local hospital.He was getting better after intravenous administration of arginine and liver protective drugs.After admission,the blood ammonia,liver function and amino acids,acylcarnitine profiling in dried blood spots,and organic acid analysis in urine were normal,and he has not recurred since restriction of protein diet.Brain magnetic resonane imaging of both patients showed cytotoxic edema of bilateral frontal lobe and insular cortex,and their genetic detection both showed c.119G＞A(p.R40H) hemizygous pathogenic mutation of OTC gene inherited from their respective mothers.Conclusion Unexplained hyperammonemia and acute encephalopathy with insular and frontal cortical involvement should be on the alert to the urea cycle disorders,especially OTCD.Early diagnosis and reasonable treatment are the key to changing the prognosis.

Objective To summarize the clinical , pathological and genetic characteristics of three patients with caveolin-3 associated myopathy and review the literatures .Methods The clinical data of three patients with caveolin-3 associated myopathy were investigated .With informed consent , we performed muscle biopsy and genetic analysis of CAV 3 and PTRF genes.Results All the three patients presented with percussion/pressure-induced rapid contraction , percussion-induced muscle mounding and mechanically induced muscle rippling.Besides, case 1 had weakness and atrophy of hand muscles .Case 2, who manifested with muscle hyperexcitability at onset , developed weakness and atrophy of distal part of lower limbs.Case 3 showed normal muscle strength and tone .All of them had myalgia or tenderness .Muscle biopsy revealed mild myogenic changes in two patients and a muscular dystrophic pattern in one . Immunohistochemical staining of caveolin-3 revealed an even deficiency in case 1 and a mosaic deficiency in cases 2 and 3.Gene analysis revealed a missense mutation ( c.80G>A, p.R27Q) in CAV3 gene of case 1. No mutations were identified in cases 2 and 3.Conclusions There is phenotypic variability in patients with caveolin-associated myopathy , including limb-girdle syndrome , rippling muscle disease , distal myopathy , muscle hypertrophy , idiopathic hyperCKemia and cardiomyopathy .Muscle biopsy and caveolin-3 staining should be performed for the above patients with muscle rippling .

Objective:To summarize and discuss the clinical manifestations, muscle pathology and gene mutation characteristics of congenital myopathy with tremor and to improve clinicians′ understanding of the disease.Methods:The clinical data of a patient of congenital myopathy with tremor who visited Qilu Hospital of Shandong University in April 2021 were reported. Enzyme histochemical staining and immunohistochemical staining were performed on the muscle tissues of the patient, and the expression level of slow skeletal myosin binding protein-C (sMyBP-C) and mitochondrial DNA copy numbers were detected by Western blotting and quantitative real-time polymerase chain reaction. The literatures of congenital myopathy with tremor reported previously were reviewed and patients reported were summarized.Results:The proband is a 35 years old male, whose clinical symptoms occurred from childhood, mainly manifested as irregular muscle vibration of the limbs and exercise intolerance, with mild proximal limb muscle weakness. Muscle biopsy showed mild myogenic damage with abnormal mitochondrial changes, and gene detection showed MYBPC1 gene c.788T>G heterozygous mutation. Further detection showed that the expression level of sMyBP-C was significantly reduced, and the number of mitochondrial DNA copies was increased in the patient. The diagnosis of congenital myopathy with tremor was clear, and the symptoms did not progress during long-term follow-up. The clinical characteristics of 26 patients from this family and 10 families previously reported were summarized, and the results indicated that tremor was a prominent clinical manifestation of this disease, combined with mild to moderate muscle weakness, which could be accompanied with varying degrees of myasthenia, delayed gross motor development and skeletal joint malformation. The symptoms usually had no progress or chronic progress. Muscle biopsy usually indicated myogenic damage, including type Ⅰ fiber predominancy, type Ⅰ fiber atrophy and central cores in type Ⅰ fibers, which may be accompanied by mild mitochondrial abnormalities. The c.788T>G mutation in the MYBPC1 gene was a hotspot mutation of congenital myopathy with tremor. Conclusions:For early-onset tremor of unknown reason with muscle weakness, hypotonia, delayed gross motor development and skeletal joint malformation, it is necessary to consider the possibility of congenital myopathy with tremor, and to further perform electromyography, muscle biopsy, and gene detection for a clear diagnosis. Muscle biopsy usually indicates myogenic damage, and the c.788T>G mutation in the MYBPC1 gene is a hotspot mutation of the disease.