Objective To explore the diagnosis and treatment of biotinase deficiency (BTD) manifested as encephalomyelopathy.Methods The clinical data of one child with BTD were retrospectively analyzed.The pertinent literatures were reviewed.Results A six-year-old male child suffered from progressive spastic paralysis of lower limbs for 3 months before admission.A similar symptoms occurred after a cold in 3-year-old.It was easy to peel skin on her hands and she had angular stomatitis.Audio visual evoked potential was detected to be abnormal in other hospital.After hospitalizion,the cerebrospinal fluid examination was normal,and MRI showed long T1 long T2 signals bilateral occipital lobe and basal ganglia region.Because the child represented medulla palsy,and so the tracheal intubation ventilator was administrated to assist ventilation.Urine gas chromatography/mass spectrometry (GC/MS) analysis showed increases of lactic acid,3-hydroxy acid,3-tiglyl glycine,methylcitric acid,and ethylene lactic acid.Serum MS/MS analysis showed that the concentrations of propionyl camitine and 3-hydroxyisovaleryl carnitine were increase obviously.The serum biotinase level was significantly decrease to 0.076 pmol/(min·mm3).The diagnosis of BTD was confirmed.After supplementation biotin,40 mg/d,the ventilator was successfully weaned on the third day,the child walked again after 2 weeks,and the rash was vanished.After 3 weeks,the head MRI showed disappearance of the original lesion,and there was no abnormal in spinal cord.The BTD gene detected by PCR direct sequencing showed a heterozygosis mutation of T172T/C in the second exon and a homozygous mutation of T1413C in the fourth exon,which was confirmed as a pathogenic mutation by pedigree verification and database query.After discharge,the oral administration of biotin 20 mg/d continued,and no abnormality was found in 2 years of follow-up.Conclusions The manifestations of BTD are complex and diverse.The analysis of urine GC/MS and serum MS/MS can assist the diagnosis.The determination of biotinase activity and gene detection of BTD can further confirm the diagnosis.Timely biotin supplementation has significant treatment efficacy.

Objective To explore the clinical,radiological and gene mutation features ofERCC8 gene in one patient with Cockayne syndrome.Methods Clinical and radiological data of a girl diagnosed with Cockayne syndrome through gene detection were retrospectively analyzed.Next-generation sequencing was used to detect genetic cause.Sanger sequencing was used to confirm the candidate variants and detect mutations in her parents and sister.ResuRs The patient showed psychomotor retardation,growth failure,special face,and light sensitivity.Neurological examination revealed noticeable developmental delay,motor impairment,spastic paralysis,and cerebellar ataxia.Brain MRI revealed symmetrical demyelination of bilateral centrum semiovale and periventricular white matter.The cerebellum was atrophic.The patient was found to have compound heterozygous mutations of c.397C＞T(p.Q133X) and c.394_398del(p.L132fs).Sanger sequencing showed these two mutations were inherited from her mother and father respectively.Conclusions Next-generation sequencing technology is a useful tool for the detection of mutation in ERCC8 gene,which is valuable for the diagnosis of Cockayne syndrome.These two mutations expanded the mutation spectrum of Cockayne syndrome in Chinese population.

Objective To examine the correlation between the gene of phosphate and tension homology deleted on chromosometen (PTEN gene) polymorphism and schizophrenia (SCZ) associated with the type 2 diabetes mellitus (T2DM ) in Shanghai Han population. Methods The study recruited 591 long-stay schizophrenic inpatients including 304 with and 287 without type 2 diabetes mellitus, 206 patients with the type 2 diabetes mellitus and 205 normal subjects from Shanghai Han population. SNPs of PTEN gene (rs1234225, rs12569998, rs1234223) were genotyped by using Taqman genotyping. The frequency distributions of allele, genotype and haplotype between groups were analyzed. Results There were significant differences in the frequency of rs1234223 genotype (P=0.01) and allele distribution (P=0.02) between the SCZ with type 2 diabetes mellitus group and the SCZ without type 2 diabetes mellitus group. The difference of genotype frequencies remained statistically significant (P=0.03) but the allele distribution was not (P=0.06) after Bonferroni correction. Haplotype analysis showed that TTC haplotype was less common in the SCZ with type 2 diabetes mellitus group than in the SCZ without type 2 diabetes mellitus group (P=0.02). Conclusions PTEN gene may be a susceptibility gene for schizophrenia with type 2 diabetes mellitus in Chinese Han population. The TTC haplotype may be a protective factor for schizophrenia with type 2 diabetes mellitus.