[Paroxysmal crying and motor regression for more than two months in an infant].

The patient was a male who was found to be abnormal at the age of 4.5 months. He presented with irritability, motor regression and opisthotonus. Brain MRI revealed bilateral abnormality in the lentiform nucleus, thalamus, deutocerebrum and cerebellar hemispheres. Novel compound heterozygous mutations of SLC19A3 gene, c.950G>A(p.G317E) and c.962C>T(p.A321V), were found in the patient. Further study showed that c.950G>A was inherited from his father and c.962C>T came from his mother. Using bioinformatics software analysis, both of the mutations were found to be harmful. His symptoms were improved remarkably after biotin, thiamine and "cocktail" therapy. One month later a brain MRI revealed that the lesions in basal ganglia and cerebellar hemispheres were improved. The patient was definitely diagnosed with biotin-thiamine responsive basal ganglia disease (BTBGD). BTBGD is a treatable autosomal recessive disease and early administration of biotin and thiamine may lead to clinical improvement.

Levetiracetam administration is correlated with lower mortality in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes: a retrospective study.

BACKGROUND: Studies on the relationship between antiepileptic drug (AED) administration and clinical outcomes in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) remain scarce. Levetiracetam (LEV) is an AED that is neuroprotective in various neurologic disorders. This study aimed to determine the impact of LEV on the outcome of MELAS. METHODS: A retrospective, single-center study was performed based on a large cohort of patients with MELAS with a history of seizures (n = 102). Decisions on antiepileptic therapies were made empirically. Patients were followed up for 1 to 8 years (median, 4 years) and divided into 2 groups based on whether LEV was administered (LEV or non-LEV). The modified Rankin scale (mRS) scores and mortality risks were analyzed in all patients. RESULTS: LEV, carbamazepine, benzodiazepines, topiramate, oxcarbazepine, valproate, and lamotrigine were administered in 48, 37, 18, 13, 11, 9, and 9 patients, singly or in combination, respectively. The mean mRS score of the LEV group (n = 48) was lower than that of the non-LEV group (n = 54; mean ±â€Šstandard deviation, 2.79 ±â€Š1.47 vs. 3.83 ±â€Š1.93, P = 0.006) up to the end of the study. Nevertheless, there was no difference in the proportion of subjects without disability (mRS ranging 0-1) between the groups (P = 0.37). The multivariate regressions revealed that LEV treatment was associated with lower mRS scores (odds ratio 0.32, 95% confidence interval [CI] 0.15-0.68, P = 0.003) and mortality rates (hazard ratio 0.24, 95% CI 0.08-0.74, P = 0.013). There was a significant difference in the Kaplan-Meier survival curves between the groups (χ = 4.29, P = 0.04). CONCLUSIONS: The LEV administration is associated with lower mortality in patients with MELAS in this retrospective study. Further laboratory research and prospective cohort studies are needed to confirm whether LEV has neuroprotective effects on patients with mitochondrial diseases.

Analyses of Genotypes and Phenotypes of Ten Chinese Patients with Wolf-Hirschhorn Syndrome by Multiplex Ligation-dependent Probe Amplification and Array Comparative Genomic Hybridization.

BACKGROUND: Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome that is typically caused by a deletion of the distal portion of the short arm of chromosome 4. However, there are few reports about the features of Chinese WHS patients. This study aimed to characterize the clinical and molecular cytogenetic features of Chinese WHS patients using the combination of multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (array CGH). METHODS: Clinical information was collected from ten patients with WHS. Genomic DNA was extracted from the peripheral blood of the patients. The deletions were analyzed by MLPA and array CGH. RESULTS: All patients exhibited the core clinical symptoms of WHS, including severe growth delay, a Greek warrior helmet facial appearance, differing degrees of intellectual disability, and epilepsy or electroencephalogram anomalies. The 4p deletions ranged from 2.62 Mb to 17.25 Mb in size and included LETM1, WHSC1, and FGFR3. CONCLUSIONS: The combined use of MLPA and array CGH is an effective and specific means to diagnose WHS and allows for the precise identification of the breakpoints and sizes of deletions. The deletion of genes in the WHS candidate region is closely correlated with the core WHS phenotype.

[Myoclonus epilepsy with ragged-red fibers: a case report and literature review].

To demonstrate the clinical manifestation, diagnosis and treatment of myoclonus epilepsy with ragged-red-fibers (MERRF), a case of MERRF was presented with review of the literature. A 4-year-7-month-old girl was diagnosed with MERRF. She had tremor, fatigue and developmental delay for more than 2 years. Laboratory tests showed that the serum and urine lactic acid and pyruvic acid increased significantly. Electroencephalogram showed diffuse and focal spike slow wave and slow wave in right central and parietal regions. Electromyogram showed neurological damage. Gene mutational analysis showed mtDNA 8344 A>G mutation. The mutational rate was 78%. Mitochondrial disease MERRF syndrome was diagnosed. Cocktails therapy with vitamins B1, B6, B12, L-carnitine, and coenzyme Q10 was administrated to the patient. MERRF is a rare disease. The diagnosis can be made by gene mutational analysis. Cocktail therapy may slow down the deterioration of the disease. Gene therapy is still experimental.

[STXBP1 gene mutation in newborns with refractory seizures].

OBJECTIVE: To study the relationship between STXBP1 gene mutations and refractory seizures with unknown causes in newborns. METHODS: The coding region of STXBP1 gene was detected using direct Sanger sequencing in 11 newborns with refractory seizures of unknown causes. RESULTS: STXBP1 gene mutation was found in 1 out of 11 patients. It was a missense mutation: c.1439C>T (p.P480L). CONCLUSIONS: STXBP1 gene mutation can be found in neonatal refractory seizures of unknown causes, suggesting a new approach of further research of this disease.

[Long-term outcome and related factors of epileptic seizures in children].

OBJECTIVE: To analyze the Long-term outcome of seizures, and to explore the effects of related factors, including the age at onset, types of epileptic syndromes, and etiological factors, etc. METHODS: The clinical data were retrospectively surveyed from 265 children with regular follow-ups for over 1 year at Peking University First Hospital (Jan. 2003 to Dec. 2006). The seizure-free rate was calculated as an at least one-year non-occurrence of seizures. The Long-term outcome of seizures was analyzed in association with factors including the age at onset, types of epileptic syndromes, and etiology. RESULTS: (1) Seizure types were clarified in all the cases, with combined types of seizures in 17. Epileptic syndromes were identified in 163/265 cases (61.5%). With regular antiepileptic drug therapy, 57.9% children with epilepsy could be seizure-free. (2) Seizure-free was demonstrated in 142/265 cases with a seizure-free rate of 53.6% in this group. (3) The age at onset was youngest in the non-efficacy group. (4) The seizure-free rate was different by syndrome types of epilepsies, with a higher seizure-free rate in idiopathic generalized epilepsy (72.4%) and benign epilepsy in children with centro-temporal spikes (65.5%), whereas a lowest rate (21.7%) in infantile spasms. (5) A significant difference of seizure-free rates was revealed in different etiological groups. Children with idiopathic epilepsy achieved higher seizure-free rate (69.2%) than those with symptomatic and cryptogenic epilepsy (45.4%). CONCLUSION: The epilepsy children with regular antiepileptic drug therapy had generally satisfactory outcome of seizures, with over half cases of seizure-free. The prognosis was demonstrated to be closely related with the etiological factors, syndrome types and age at onset.

[Clinical and genetic characteristics of glucose transporter type 1 deficiency syndrome].

OBJECTIVE: To analyze the clinical and SLC2A1 gene mutation characteristics of glucose transporter type 1 deficiency syndrome. METHOD: The detailed clinical manifestations of six cases were recorded. The laboratory tests including EEG, MRI, blood chemistry, and lumbar puncture were performed. SLC2A1 gene mutations were analyzed by PCR, DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). RESULT: Patient 1, 2 and 3 had classical clinical symptoms including infantile onset seizures, development delay. Patient 4, 5 and 6 had non-classical clinical symptoms including paroxysmal behavior disturbance, weakness, ataxia, lethargy, especially after fasting or exercise, without severe seizures. The plasma glucose levels were normal. The CSF glucose levels decreased in all the six cases, ranged from 1.10 mmol/L to 2.45 mmol/L, the mean level was 1.68 mmol/L. The CSF glucose/plasma glucose ratios decreased, ranged from 0.16 to 0.51, the mean ratio was 0.34. Four patients had normal EEG. Two patients had focal and diffuse epileptiform discharge, and one of them also had paroxysmal occipital or generalized high-amplitude slow waves during awake and sleep time. MRI abnormalities were found in three patients, patient 1 with mild brain atrophy, patient 3 with bilateral ventricle plump, and patient 4 with high signals in T2 in the frontal and occipital white matter, interpreted as hypomyelination. SLC2A1 gene mutations were found in six cases. Patient 1 has large scale deletion in exon 2. In patient 2 to 6, the mutations were c.741 G>A (E247K), 599delA, 761delA, c.1148 C>A (P383H), c.1198 C>T (R400C) respectively. Two patients were treated with ketogenic diet. The seizures disappeared and development became normal. Three patients responded to frequent meals with snacks. One patient refused any treatments, the symptoms continued to exist. CONCLUSION: The clinical manifestations of glucose transporter type 1 deficiency syndrome are varied. The common symptoms included infantile onset seizures and various paroxysmal events. These neurologic symptoms generally fluctuated and were influenced by factors such as fasting or fatigue. This feature could be a very important clue for the diagnosis of GLUT1-DS. Lumbar puncture is recommended in patients with episodic CNS symptoms especially after fasting. GLUT1-DS is a treatable neurometabolic disorder, early diagnosis and treatment may improve the prognosis of the patients.

[Clinical, pathological and molecular biological characteristics of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode in children].

OBJECTIVE: To delineate the characteristics of the clinical manifestation, pathology of skeletal muscle and gene mutations of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode (MELAS) in children. METHOD: The clinical manifestation, laboratorial data, brain images, muscle pathology and mitochondrial gene mutations were analyzed in 24 patients with MELAS who were diagnosed in Department of Pediatrics, Peking University First Hospital. Their prognosis was evaluated by following up. RESULT: Symptoms of central nervous system such as stroke-like episodes, vomiting, convulsion and headache were present in all the 24 cases. Nine cases had the symptoms of myopathy. Twenty cases had developmental delay. Short stature, being thin and hairy was very common in these cases. Serum lactate level increased in all the cases, pyruvate increased in 17 cases. Elevated CSF lactate was found in 2 cases. Magnetic resonance imaging (MRI) was performed on 24 cases, out of them 23 were abnormal. The lesions mainly involved cerebral lobes. Occipital lobe was the most common site of lesions. Computed tomography (CT) was performed on 13 cases, low density lesions were present in 10 cases, basal ganglia calcifications in 5 cases. Muscle biopsy was performed on 8 cases, ragged-red fibers (RRF) were found in 4/8 cases, and abnormal accumulation of mitochondria were found in 3/8 cases. The mtDNA gene mutational analysis showed A3243G mutation in these patients. The mutation rates varied from 11.6% to 75.0%. The same mutation were found in 4/5 mothers who had the genetic tests, and the mutation rates of the mothers varied from 15.0% to 23.6%. The clinical information of 11 cases was available through recent following up. Three cases died, the others had some degrees of mental retardation. CONCLUSION: Children with MELAS had various clinical manifestations. Central nervous system and skeletal muscle were usually involved. Short stature and hypertrichosis were common signs. The prognosis of this disease was disappointing. mtDNA A3243G was the most common mutation in MELAS. Fully understanding the characteristics of its clinical manifestation, laboratory tests, brain image, muscle pathology and molecular features can be helpful to the early diagnosis and treatment.

Caring for a child with severe intellectual disability in China: the example of Rett syndrome.

PURPOSE: Rett syndrome is one of several genetic disorders known to cause severe intellectual and physical disability, mostly in girls. Girls affected by Rett syndrome appear to develop normally in the first 6 months of life, after which the usual clinical presentation comprises regression of communication and hand skills, the appearance of hand stereotypies and impaired gait. Intellectual disability affects more than 1.5% of the population of children in developing countries yet we know little about the daily lives and support services available for them and their caregivers. METHOD: This qualitative study explored the daily experiences of 14 mothers and one grandmother caring for a child with Rett syndrome in China via telephone interviews. RESULTS: Participants reported a lack of education, rehabilitation and support services available to them. Limited access to information reduced families' capacity to adequately meet the needs of their child. These gaps were further exacerbated by discrimination and perceived stigma from some members of the community. CONCLUSIONS: Additional support services and educational programs at the governmental level can improve the quality of life of persons with an intellectual disability and their families and programs involving community participation in the care of people with disabilities may help to address discrimination.

Genotype/phenotype of 6 Chinese cases with Niemann-Pick disease type C.

UNLABELLED: Niemann-Pick disease type C (NP-C), caused by mutations of either NPC1 or NPC2 gene, is an inherited lysosomal lipid storage disorder that is difficult to be diagnosed and treated. NP-C is rarely reported in China and so far very few literatures are available for Chinese clinical workers. To better characterize this disease in China and improve genetic counseling, mutational analyses of NPC1 gene were carried out in 6 unrelated Chinese patients. METHODS: Clinical data of the probands from 2007 to 2010 were collected and analyzed. All exons of NPC1 were analyzed by direct sequencing. RESULTS: The six cases, four males and two females, included three cases of late infantile subtype and three cases of juvenile subtype. Case one and case six had siblings who suffered from the same disease. The onset of clinical symptoms varied from three to ten years old, and they included progressive cognitive and language impairment, and motion retrogradation. All were caught by focal or generalized seizures from one to four years after the onset. Vertical supranuclear gaze palsy, dysarthria, dysphagia, internal rotation and adduction of bilateral hands and splenomegaly occurred gradually during the disease progression. Five patients had laughter-cataplexy. MRI indicated mild brain atrophy. Sea blue cells and Niemann-Pick cells were presented in bone marrow smears. Activity of acid sphingomyelinase was normal or only slightly lower than controls. Supporting and symptomatic treatments could improve some of the clinical signs. We identified 10 different NPC1 mutations were identified in 12/12 alleles, 3 of which are described for the first time. All mutations were missense mutations, which located throughout the gene with five clustering in the cysteine-rich luminal domain. Homozygous mutation of S865L correlated with a relatively severe juvenile neurological form. CONCLUSIONS: NP-C is a rare autosomal recessive lysosomal storage disease that affects intellectual development of children, causing dementia, vegetative state and eventual death. The awareness of NP-C should be raised in the Chinese population. The typical clinical features of this disease include vertical supranuclear gaze palsy, seizures and cataplexy. Laboratory features include the presence of sea blue cells and Niemann-Pick cells in bone marrow smears. NPC1 mutation can be identified in most of these patients and most of them are missense mutations.

[Valproic acid-induced idiosyncratic liver injury in 4 cases].

OBJECTIVE: Children with refractory epilepsy who suffered from severe liver function impairment during valproic acid (VPA) treatment at routine dosage were studied. The clinical manifestations and therapeutic approaches were investigated in order to improve its diagnosis and management. METHOD: Clinical information as well as features and management of 4 inpatients who were suffered from intractable epilepsy with severe liver function impairment induced by VPA since 2006 were collected and analyzed, including age of onset of epilepsy, VPA using age and the time when liver injury occurred, clinical manifestations, auxiliary examinations and management. RESULT: Among the 4 cases, three were male and one was female. The admitted age ranged from 1 - 9 years and 1 month. The course of disease was 25 d - 6 months. They manifested as refractory epilepsy of epilepsia partialis continua which was difficult to control. After using VPA for 62 d (50 - 76 d), all developed severe impairment of liver synthetic function which was not related to the concentration of VPA. One was diagnosed with Alpers syndrome, two were suspicious of Alpers syndrome, and the other was diagnosed gliocytoma after brain biopsy. VPA was stopped immediately and symptomatic therapies were used. Other than that, intravenous injection of L-carnitine in 3 cases recovered the liver function. CONCLUSION: VPA-associated severe hepatotoxicity can manifest first as impaired liver synthetic function. Besides alanin transaminase and aspartate transaminase, the liver synthetic function test is more important than monitoring of liver enzymatic functions in monitoring for the hepatotoxicity. Intravenous injection of L-carnitine in early stage showed good treatment effect.

Barriers to diagnosis of a rare neurological disorder in China--lived experiences of Rett syndrome families.

Rett syndrome is a rare neurological disorder affecting girls and usually caused by a mutation on the MECP2 gene. It is estimated that approximately 1,000 girls are born every year in China with Rett syndrome but far fewer have received a diagnosis. Fourteen of 74 Chinese families known to the International Rett Syndrome Phenotype Database participated in this qualitative study. Telephone interviews were conducted in Mandarin to explore pathways to a diagnosis of Rett syndrome in China and associated barriers. Families consulted multiple clinical centers and eventually received a diagnosis at a centrally located hospital. Over the course of this pathway, families encountered lack of knowledge and diagnostic expertise for Rett syndrome at local levels and a heavily over-burdened hospital system. There was a paucity of information available to guide management of this rare disorder after the diagnosis had been received. Our study suggests that the frustrations experienced by families could in part be addressed by the provision of information, education, and training related to Rett syndrome for clinicians, additional resources to allow clinicians to request genetic testing for confirmation of the clinical diagnosis and for information and support services for families.

Niemann-Pick disease type C: analysis of 7 patients.

BACKGROUND: Niemann-Pick disease type C (NP-C), derived from mutation of the NPC1 or NPC2 gene, is one of the recessive lysosomal lipid storage disorders that are difficult to diagnose and treat. Since NP-C has been rarely reported in China, we reviewed 7 patients with NP-C. METHODS: The 7 patients had been diagnosed with NP-C from 2007 to 2010 at our department and their laboratory and clinical data were analyzed. RESULTS: The 7 patients, 5 males and 2 females, included 4 patients of late infantile subtype and 3 patients of juvenile subtype, in which patients 2 and 3 were siblings. Their clinical symptoms occurred from 4 to 10 years of age, exhibiting as progressive cognitive and language impairment as well as motor retrogression. Six patients were caught by focal or generalized seizures from 1 to 4 years after the onset of the disease. Vertical supranuclear gaze palsy, dysarthria, dysphagia, internal rotation and adduction of bilateral hands and splenomegaly occurred following the progress of clinical symptoms. Five patients had laughter-cataplexy. MRI showed mild brain atrophy in 6 patients. Reduction of total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol occurred in 6 patients. Sea-blue cells and Niemann-Pick cells were found in bone marrow smears. The activity of acid sphingomyelin enzyme was normal or only slightly lower. Supporting or symptomatic treatment improved common clinical symptoms. CONCLUSIONS: NP-C is a rare autosomal recessive inherited lysosomal storage disease that affects the intellectual development of children and may lead to dementia, vegetative state or death. Clinical features of this disease include vertical supranuclear gaze palsy, seizures and cataplexy. Laboratory features include abnormal plasma cholesterol level, and sea-blue cells and Niemann-Pick cells in bone marrow smears. The treatments of the disease include supporting or symptomatic administration.

[Electroclinical features of myoclonic-atonic epilepsy].

OBJECTIVE: To summarize the electroclinical characteristics of myoclonic atonic epilepsy (MAE) in children. METHOD: The clinical data, video electroencephalogram (EEG) and simultaneous electromyography (EMG) of MAE patients were analyzed. The treatment and its effects were followed up. RESULT: In 47 MAE patients, 25 had a history of febrile seizures (FS), 20 had a family history of FS or epilepsy. All patients had a normal development before the illness. The age of afebrile seizure onset was between 1.4 years to 5.8 years. The first seizure was generalized tonic-clonic seizure (GTCS) in 41 patients (87.2%). All patients had multiple seizure types, including 47 GTCS (97.9%), 34 myoclonic atonic seizures (72.3%), 47 myoclonic seizures (100%), 32 atonic seizures (68.1%), 36 atypical absences (76.6%) and 3 tonic seizures (6.4%). EEG backgrounds were slow or parietal θ rhythm, interictal EEG showed 1-4 Hz (predominant 2-3 Hz) generalized spike and wave or poly spike and wave discharges in all cases. Seizures were controlled by antiepileptic drugs (AEDs) in 41 patients (87.2%). Valproate was used in 37. Lamotrigine was used in 26. Mild mental retardation was observed in 10 children after the onset of the illness. CONCLUSION: The clinical features of MAE included the following: the development was normal before the onset of the illness; the onset of seizure type was often GTCS. All patients had multiple generalized seizure types. Myoclonic atonic seizure was its characteristic seizure type. EEG showed generalized discharges. Early diagnosis and rational choice of AEDs are important for getting a better prognosis.

[Association of genetic polymorphisms in methionine metabolism genes with X-linked adrenoleukodystrophy].

OBJECTIVE: To investigate the association of the polymorphisms of methionine metabolism genes and the phenotype of X-linked adrenoleukodystrophy (X-ALD) and clinical severity. METHODS: The clinical information of 120 X-ALD patients were analyzed and three genetic variants involved in the methionine metabolism, including cystathionine beta-synthase (CBS) c.844_855ins68, 5-methyltetrahydrofolate-homocysteine-S-methyltransferase (MTR) c.2756A to G, and transcobalamin 2 (TC2) c.776 C to G were analyzed by polymerase chain reaction and sequencing. The association between these polymorphisms and phenotype of X-ALD was studied. RESULTS: The frequency of GG genotype of the TC2 c.776 C/G was higher in patients with central nervous system(CNS) demyelination than in controls (P= 0.012). However, the other two polymorphisms did not show any significant associations with the phenotypes. CONCLUSION: The GG genotype of TC2 c.776 C/G may contribute to X-ALD phenotype.

[Clinical characteristics and follow-up management of 135 children with myasthenia gravis].

OBJECTIVE: To investigate and analyze the clinical manifestations, classification, therapeutic approaches and follow-up of myasthenia gravis (MG) in children in order to improve its management and prognosis. METHODS: Clinical information of 135 children with MG, who were diagnosed between January 1993 to January 2008, were collected and retrospectively analyzed. And prospective following-up of these patients were conducted. RESULTS: Among the 135 cases, 59 were males and 76 females, giving the ratio of M/F around 1:1.3. Totally, 115 cases (85.2%) were type I MG (ocular type), of which only 4.2% developed to generalized type during the subsequent clinical course. Type II MG (generalized type)was found in 18 cases (13.4%) and type III MG in two cases(1.5%). The onset age ranged from 5 month to 15 years, with 50.3% before three years and 80.7% before seven years. Upper respiratory tract infection was presented in 26.7% (36/135) of the sick children before the onset of MG. Among the 106 children being followed up, recurrence of the disease identified in 50.9% and the number of relapse ranged from 1 to 9. Altogether, 40.19% (43/106) of the cases were positive for anti-acetylcholine receptor antibodies (AchR-Ab) on the initial examination, and the AchR-Ab postitive rate showed no difference among different clinical subtypes and states. However, during the follow-up, 53% (9/17) of the recurrent cases, who were negative at the first onset, turned to be positive, and 37.97% (30/79) were positive for repetitive nerve stimulation in electromyogram test. There were 71 % (45/63) of all the cases showed reduced levels of CD4+ and/or CD3+ and/or CD8+. Thymus proliferation was found in 5.93% (8/135) through CT scan and thymoma in 1.48% (2/135). Steroids and anti-cholinesterase administration were effective in most cases with good prognosis. CONCLUSION: Childhood MG, mainly type I, is relatively common in China, with specific characteristics which are different from western patients or adult MG in morbidity, sex distribution, progress, laboratory examination and treatment. The prevalence of myasthenia gravis crisis and mortality rate in MG children is low, and few are accompanied with thymoma. Most MG cases have a satisfied prognosis and few have neuropsychic sequela.

[Clinical characteristics of Huntington disease in two pedigrees and analysis of expanded CAG trinucleotide repeat].

OBJECTIVE: To understand the clinical and genetic features of Huntington disease (HD). METHODS: The clinical data of HD cases from 2 Chinese families were analyzed and trinucleotide repeat in the IT15 gene were investigated in 9 of the two families by polymerase chain reaction and GeneScan. RESULTS: Among the two pedigrees, 6 cases were ascertained as HD by genetic test. Genotypes of IT15 were heterozygous in these HD patients. CAG repeat of the patients in the HD chromosome were 40-78. In the two pedigrees, the onset age was earlier in the subsequent generations than that of their fathers. In pedigree 2, the onset age was inversely correlated with CAG repeat number. One out of the 6 cases was juvenile-onset type of Huntington disease, whose clinical symptoms were different from those of the adult-onset cases, especially the hypertonic manifestation. CONCLUSION: HD is an autosomal dominant neurodegenerative disorder with genetic anticipation caused by enlargement of CAG repeat in IT15 gene. The clinical manifestation is different between the juvenile-onset and the adult-onset. The number of CAG repeat is inversely correlated with the onset age and clinical severity.

[Value of latex agglutination test in the diagnosis and treatment of cryptococcal meningitis in children].

OBJECTIVE: To evaluate the value of cryptococcal latex agglutination test in the diagnosis and treatment of cryptococcal meningitis in children. METHODS: The clinical data of 10 children with cryptococcal meningitis were retrospectively studied. Cryptococcal meningitis was confirmed based on clinical manifestations, India ink stain, cryptococcal latex agglutination test or cryptococcal culture. The outcome of antifungal treatment and the changes of latex agglutination test titer were followed up for 2 to 4 years. RESULTS: Latex agglutination test and/or India ink stain were positive (titer 1 : 64-1 : 1024) in 8 patients in the first examination of cerebrospinal fluid. In the other 2 patients, latex agglutination test was positive (titer 1 : 256) in the fourth examination of cerebrospinal fluid in one, and India ink stain was positive in the eleventh examination in the other. After antifungal treatment, six patients were cured, two patients died, and two patients were lost to follow-up. The positive cryptococcal latex agglutination test (titer 1 : 2-1 : 16) was seen respectively in six, three, two and one cured patients 6 months, 1 year, 2 years and 4 years later. CONCLUSIONS: The cryptococcal latex agglutination test of cerebrospinal fluid is valuable for the quick and early diagnosis of cryptococcal meningitis; however, the decision of withdrawal of antifungal treatment should not rely on the results of the test.

Molecular characterization of SMN copy number derived from carrier screening and from core families with SMA in a Chinese population.

Screening for carriers of spinal muscular atrophy (SMA) is necessary for effective clinical/prenatal diagnosis and genetic counseling. However, a population-based study of SMA prevalence in mainland China has not yet been conducted. In this study, the copy number of survival motor neuron (SMN) genes was determined in 1712 newborn cord blood samples collected from southern China and from 25 core families, which included 26 SMA patients and 44 parents, to identify SMA carriers. The results presented 13 groups with different SMN1/SMN2 ratios among 1712 newborn individuals, which corresponded to 1535 subjects with two copies of SMN1, 119 with three copies of SMN1, 17 with four copies of SMN1, and 41 with a heterozygous deletion of SMN1 exon 7. Simultaneously, two '2+0' genotypes and two point mutations were found among the 44 obligate carriers in the core families, including a novel SMN1 splice-site mutation that was identified in the junction between intron 6 and exon 7 (c. 835-1G>A). These results indicated that the carrier frequency is 1/42 in the general Chinese population and that duplicated SMN1 alleles and de novo deletion mutations are present in a small number of SMA carriers. In addition, we developed and validated a new alternative screening method using a reverse dot blot assay for rapid genotyping of deletional SMA. Our research elucidated the genetic load and SMN gene variants that are present in the Chinese population, and could serve as the basis for a nationwide program of genetic counseling and clinical/prenatal diagnosis to prevent SMA in China.

[Analysis of the parental origin of MECP2 mutations in patients with Rett syndrome].

OBJECTIVE: To identify the parental origin of methyl-CpG-binding protein 2 (MECP2) gene mutations in Chinese patients with Rett syndrome. METHODS: Single nucleotide polymorphisms (SNPs) in intron 3 of the MECP2 gene were analyzed by PCR and sequencing in 115 patients with Rett syndrome. Then sequencing of the SNP region was performed for the fathers of the patients who had at least one SNP, to determine which allele was from the father. Then allele-specific PCR was performed and the products were sequenced to see whether the allele from father or mother harbored the mutation. RESULTS: Seventy-six of the 115 patients had at least one SNP. Three hot SNPs were found in these patients. They were: IVS3+22C >G, IVS3+266C >T and IVS3+683C>T. Among the 76 cases, 73 had a paternal origin of MECP2 mutations, and the other 3 had a maternal origin. There were multiple types of MECP2 mutation of the paternal origin, including 4 frame shift, 2 deletion and 67 point (56C >T, 6C >G, 2A >G, 2G >T and 1A >T) mutations. The mutation types of the 3 patients with maternal origin included 2 frame shift and 1 point (C >T) mutation. CONCLUSION: In Chinese RTT patients, the MECP2 mutations are mostly of paternal origin.