Clinical application of proton magnetic resonance spectroscopy in children with idiopathic epilepsy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>This study examined the biochemical metabolism by proton magnetic resonance spectroscopy ('H-MRS) in order to explore the value of 'H-MRS in idiopathic epilepsy in children.</p><p><b>METHODS</b>Thirty-three children with idiopathic epilepsy (14 cases with history of febrile seizures and 19 cases without) and six normal controls experienced MRI of the skull and brain and single-voxel 'H-MRS examinations of the hippocampi-temporal lobe. The signal intensities of N-acetylaspartate (NAA), eatine+phosphocreatine (Cr), choline-containing compounds (Cho) and lactate (Lac) and the ratios of NAA/ (Cho+Cr) and Lac/Cr were compared between the patients and normal controls.</p><p><b>RESULTS</b>MRI examination showed that only one child with epilepsy had myelin dysplasia. 'H-MRS examination showed that the ratio of NAA/ (Cho+Cr) in the epilepsy group was lower than that in the control group (0.64+/-0.07 vs 0.73+/-0.05; P<0.01). The epileptic children with history of febrile seizures had a more decreased ratio of NAA/ (Cho+Cr) compared with those without the history (0.61+/-0.07 vs 0.66+/-0.06; P<0.05). There were no significant differences in the ratio of Lac/Cr between the epilepsy and the control groups.</p><p><b>CONCLUSIONS</b>'H-MRS may provide early information on brain injury sensitively and non-invasively in children with epilepsy. It may be used for diagnosis and prognosis evaluation of epilepsy.</p>

Quantification of phenylalanine in the brain of patients with hyperphenylalaninemia by (1)H magnetic resonance spectroscopy / 中华儿科杂志

<p><b>OBJECTIVE</b>Hyperphenylalaninemia (HPA) is an inborn error of metabolism in which the hydroxylation of phenylalanine (Phe) to tyrosine is disturbed. Accumulation of Phe leads to severe mental and psychomotor retardation. (1)H magnetic resonance spectroscopy ((1)HMRS) is a novel non-invasive method to quantitate the brain metabolites besides Phe concentration in HPA patients. And it could be acquired conveniently on clinical MRI routine scanners. This study aimed to investigate the correlation between blood Phe ([Phe](blood)) and [Phe](brain), the characteristics of blood-brain Phe metabolism and its impacts on mental retardation.</p><p><b>METHOD</b>Totally 32 untreated patients diagnosed with HPA were studied, including 18 boys and 14 girls (age ranging from 33 days to 13 years). The patients were divided into two groups: elder than 4 months old (n = 22) and younger than 4 months old (n = 10). (1)HMRS were performed in all patients. [Phe](brain) were measured by absolute [Phe](brain) using Creatinine as an internal reference. [Phe](blood) were measured and developmental quotient (DQ) or intelligence quotients (IQ) were evaluated.</p><p><b>RESULT</b>(1) [Phe](brain) measured by (1)HMRS ranged from 0.0640 to 0.6296 (M = 0.1542) while the [Phe](blood) was from 0.3804 to 2.5140 mmol/L (M = 1.5210 mmol/L) in all the 32 cases of HPA patients. (2) There was a positive linear correlation (r = 0.6103 (P < 0.01)) between [Phe](blood) and [Phe](brain). And there were interindividual differences in [Phe](brain) in several patients. (3) Variable mental retardation were observed in 23/32 cases in this study. (4) There was a negative correlation between [Phe](blood) and [Phe](brain) to the mental retardation (r(blood) = -0.5045, r(brain) = -0.6471 (P < 0.01)) in 22 cases of the HPA patients older than 4 months. And [Phe](brain) had more significant correlation with mental development than [Phe](blood).</p><p><b>CONCLUSION</b>The [Phe](blood) could correspondingly represent the [Phe](brain) in most HPA patients. The Phe concentration could reflect the degree of mental retardation substantially in 22 cases with HPA older than 4 months. And the [Phe](brain) could more accurately illustrate it. (1)HMRS can be used to quantitate intracerebral Phe concentrations non-invasively in HPA patients. Preliminary findings suggest that interindividual variations in the kinetics of Phe uptake and metabolism do exist. (1)HMRS has great clinical significance in understanding the mechanism of HPA patient's mental retardation, providing proper objective standards for better diagnosis and treatment of HPA patients.</p>

Clinical study of tetrahydrobiopterin responsive phenylalanine hydroxylase deficiency in southern and northern Chinese patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze characteristics of different hyperphenylalaninemia (HPA) and to discuss the clinical difference between southern and northern Chinese patients with tetrahydrobiopterin (BH4) responsive phenylalanine hydroxylase (PAH) deficiency.</p><p><b>METHODS</b>(1)BH4 (20 mg/kg) loading test was performed in all 108 HPA patients. These patients, 63 males and 45 females, were at a mean age of 7.05 months. A combined phenylalanine (Phe) and BH4 loading test was carried out in the patients who had a basic blood Phe concentration less than 600 micromol/L. The urine pterine profile analysis and the dihydropteridine reductase (DHPR) activity in dry blood filter spot were analyzed simultaneously. (2)BH4 responsive patients were divided to southern and northern groups by their parent's native place and geographic boundary determined by Changjiang River. The change of Phe concentration after BH4 loading test was compared between the two groups.</p><p><b>RESULTS</b>(1)Among the 108 HPA cases, 36 patients (33.3%) were BH4 responsive PAH deficiency, 49 (45.4%) were non-BH4 no responsive phenylketonuria (PKU)and 23(21.3%)were BH4 deficiency (BH4D). The Phe concentration of patients with BH4 responsive PAH deficiency decreased by 49.24% and 65.35% at 8 h and 24 h after oral BH4, 23 in southern group and 13 in northern group among 36 patients. (2)The mean Phe concentration at 24 h after loading test in southern and northern groups were (217.02+/-189.03) micromol/L and 458.75+/-342.54 micromol/L respectively (P<0.05), although the decrease percent of plasma Phe concentration at 2 h, 4 h, 8 h, 24 h was no distinct difference between southern and northern groups (P>0.05).</p><p><b>CONCLUSION</b>Most of mild and moderate HPA patients affected by PAH deficiency show plasma Phe concentration decrease >30% in 24 h after oral BH4 20 mg/kg, few are classic PKU. The responsiveness to BH4 is no difference between southern and northern Chinese patients with BH4 responsive PAH deficiency according to the decrease percent of plasma Phe concentration, although the Phe concentration is lower in southern patients than that in northern patients.</p>

Brain white matter lesions of children with phenylketonuria before and after treatment / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To observe brain white matter changes in children with late-treated phenylketonuria (PKU) before and after receiving treatment.</p><p><b>METHODS</b>This study included 19 PKU patients (aged 34-410 weeks) who were administered a low-phenylalanine diet (< 15-50 mg/kg daily) for 8-16 months. The brain MR imaging with spin-echo T1-weighted and T2-weighted sequences in coronal and axial planes was taken before and after treatment. The white matter abnormalities (T2WI high signal intensity) were graded based on the Thompson grading system. Meanwhile the intelligence quotient (IQ) or developmental quotient (DQ) was tested by the Gesell's Intelligence Scale.</p><p><b>RESULTS</b>All 19 PKU patients presented with the brain white matter lesions, manifesting abnormally high T2-signal intensity in the periventricular region around anterior and posterior horns of both lateral ventricles. Different extents of mental retardation were also observed in the 19 patients. The low phenylalanine diet treatment decreased the average grade of abnormal T2-signal intensity from 2.59 to 1.76 (P < 0.05). The mean IQ or DQ improved from 44.8 to 61.6 after treatment (P < 0.05). There was some correlation between the amelioration of brain white matter lesions and IQ or DQ.</p><p><b>CONCLUSIONS</b>The patients with late-treated PKU have a higher occurrence of the brain white matter lesions and mental retardation. A low-phenylalanine diet treatment can partly improve the abnormalities. Brain white matter lesions may play a part in mental retardation.</p>

Delayed Brain Myelination in Children with Phenylketonuria Complicated with Epilepsia / 实用儿科临床杂志

Objective To observe the delayed brain myelination of children with phenylketonuria(PKU)combined with epilepsia,and explore effectiveness of the treatment and provide an objective criteria for patient recovering evaluation.Methods There were 42 PKU patients,aged 3 to 72 months were selected.The concentration of phenylalanine tested by high pressure liquid chromatography was greater than 1.2 mmol/L in blood,diagnosed as PKU.According to electroencephalogram and clinical symptom,21 cases were diagnosed as epilepsy,the other 21 cases were used as control group.All patients were taken MRI before treatment.Myelination in 10 sections(cerebellum,pons,mesencephalon,internal capsule posterior limb,corpus callosum,internal capsule anterior limb,occipital lobe,parietal lobe,temporal lobe,frontal lobe)were evaluated.Results Delayed myelinations were located mainly in the cerebral lobes and corpus callosum,average delayed incidence of the 10 region was 44.8% in epilepsy group and 30.9% in control group.The incidence of the corpus callsum was 80.9% in epilepsy group,52.4% in control group,the number of sections of delayed myelination showed statistically significant between 2 groups(P

Analysis of High Risk Factors for Metabolic Syndrome in Obese Children with Acanthosis Nigricans / 实用儿科临床杂志

Objective To explore the high risk factors of metabolic syndrome(MS) in obese children with acanthosis nigricans.Me-thods Body mass index(BMI),blood lipid including triglyeride(TG) and cholesterol(CHO),low density lipoprotein-cholesterol(LDL-C),blood pressure,the level of fasting blood glucose(FBG) and 2 h after oral glucose tolerance test blood glucose(OGTT 2h BG) and the level of fasting insulin(FINS) and 2 h after oral glucose tolerance test insulin (OGTT 2h INS) and homeostasis model appraisal insulin resis-tance index(HOMA-IR) were measured and compared between 25 obese children with acanthosis nigricans[male 15,female 10;aged 8.4-16.0,mean 10.6 years old,weight (72.11?17.66) kg;height (155?14) cm]and 32 normal healthy children[male 18,female 14;aged 7.6-15.8,mean 9.8 years old]in department of pediatric during 1 year.HOMA-IR were also analyzed.Ultrasonic inspections for liver were performed in those children.Results BMI,TG,LDL-C and blood pressure in the obese group were significantly higher than those in the normal control group(Pa0.05).Eighty-four percent of patients in obese children with acanthosis nigricans were diagnosed adiposis hepatica by ultrasonograph.Conclusions The increasing BMI,insulin resistance,blood lipid disorder and blood pressure increase in obese children with acanthosis nigricans are the high risk factors of MS,the close followed-up and treating this kind of obese children can acquire MS early and be helpful to postpone the progress of diabetesⅡ and cardiovascular diseases.

Clinical Phenotype of Different Hyperphenylalaninemia Patients / 实用儿科临床杂志

Objective To explore clinical characteristics of phenylalanine hydroxylase(PAH) deficiency in differential diagnosis among hyperphenylalaninemia(HPA) patients and compare the responses to diet treatment in HPA patients.Methods Tetrahydrobiopterin(BH4,20 mg/kg) loading test or combined phenylalanine(Phe,100 mg/kg) and BH4 loading test was carried out among 44 HPA patients.The urine pterine profile analysis and dihydropteridine reductase(DHPR) activity in dry blood filter spot were analyzed simultaneously.Electroencephalogram(EEG) and average full scale development quotient(DQ) were performed in all patients.PAH deficiency patients were given low Phe diet treatment to decrease Phe level for 120-360 ?mol/L and followed up their Phe tolerance.Results Twelve BH4 responsive PAH deficiency patients were diagnosed who were 7 males and 5 females,mean age was 7.8 months.Their metabolic phenotype was moderate or mild HPA.Diet control could decrease Phe level among BH4 deficiency patients but not prevent their neural damage and their EEG abnormal rate was higher.BH4 responsive patients had higher DQ than others and their Phe tolerance increased during diet treatment.Conclusions BH4 responsive PAH deficiency patients can obtain better purpose with diet recipe.The differential diagnosis for BH4 deficiency shall be carried out in all patients with HPA as soon as possible.

An eighteen-year study on phenylketonuria / 中国医学科学院学报

A study on phenylketonuria (PKU) has been carried out in China-Japan Friendship Hospital since 1984. The results revealed that: (1) Totally 603 patients with PKU were diagnosed and treated in the hospital from October 1984 to September 2002. Among which 136 cases were identified by neonatal screening and treated within 3 months. One hundred and ninety-five cases were treated when the children were 3-12 months of age. Another 272 PKU children were diagnosed when they were more than 1 year old. All of these late-treated cases had some signs and symptoms of PKU. Mental retardation was found in 467 cases and various patterns of seizures in 119 cases. After treatment with low-phenylalanine diet, the follow-up for early-treated patients revealed that their physical and mental developments were normal. In late-treated patients, abnormal behaviour was significantly improved and their developmental quotient were elevated. Prenatal gene diagnosis of PKU risk foetus in 22 PKU families was successfully performed. (2) Urinary pterins obtained from 369 HPA patients were measured by HPLC. Twenty two patients with BH4 deficiency have been recognized. Six single base mutations were detected in 18 unrelated northern Chinese BH4 deficiency families, and the mutations at nucleotides 259C-->T and 286G-->A were common mutations. Eighteen BH4 deficient patients were treated with BH4, L-dopa and 5-hydroxytryptophan, and the results were satisfactory. (3) The abnormal rate of EEG was high in untreated patients with PKU, mainly showing epileptiform discharges and partly showing background activity abnormality. The most frequent finding was patchy areas of increased signal intensity in white matter on MRI in the brain of PKU patients, while delayed myelination and brain agenesis were often detected. After dietary treatment, follow-ups with EEG and MRI revealed that the abnormalities were decreased significantly. (4) The relationship between genotype and intellectual phenotype was examined in 29 late-treated patients with classical PKU. It was found that the genotype of 22 patients were compatible with intellectual phenotype and not well matched in 7 cases. The result indicate that the genotype was well matched with intellectual phenotype in classical PKU patients.

Clinical Significance of Mycoplasma Pneumoniae Antibodies IgM Positive with High Titers / 实用儿科临床杂志

Objective To explore the clinical significance of mycoplasma pneumoniae(MP) antibody IgM positive with high titers.Methods Two hundred and sixty-seven cases of respiratory tract infections of MP with MP-IgM positive were confirmed in our hospital during Jun.2005 to Aug.2008,of which 63 cases with significantly increased titers of MP-IgM antibodies(MP-IgM≥1:1 280).A prospective observation and later analysis of the clinical manifestations of the 63 cases were carried out.Results 1.Among 63 cases,6 cases were diagnosed as upper respiratory tract infection,12 cases as acute bronchitis and 45 cases as pneumonia,respectively.2.The 63 cases pre-sented mainly with fever and cough,of them 59 cases had fever and 45 cases with paroxysmal cough,39 cases could be found crackles on physical examination.3.Extrapulmonary manifestations could be found in many cases,including heart complications in 21 cases,abnormal liver functions in 35 cases,gastrointestinal manifestations in 22 cases,neurological manifestations in 1 case,dermatological disorders in 7 cases and renal manifestations in 3 cases.4.Patterns of chest X-ray findings of the 63 cases with MP infections were varied,of which 45 cases showed pulmonary abnormality.Chest X-ray findings of the 45 children included 12 cases with interstitial infiltration,6 cases with lobar condensation,15 cases with patch shadows,4 cases with enlarged porta pulmonis and 8 cases with reticulonodular infiltrates.Three cases were complicated with pleural effusion and 2 children with segmental atelectasis.5.The cases were given azithromycin,10 mg/(kg?d),a daily dose for 5 days and intermitted for 4 days.All cases repeated the treatment courses for 1 to 4 times.The mean duration of fever was 6.6 days,cough could last 11.7 days and the crackles on physical examination could not be found 7.5 days later after treatment.The abnormality of chest X-ray findings dissolved in 38 cases 2-3 weeks later after treatment.Conclusions Cases of MP infections with high titers of MP-IgM positive had severe symptoms,of which more than 90% patients presenting with lower respiratory tract infections,mainly with pneumonia.Recovery of chest radiological finding was posterior to clinical improvement,so timely and regular chest X-ray examinations were essential after treatment and could avoid the false ceasing of treatment of the cases.Patients of MP infections with high titers of IgM antibodies positive have good prognosis.

Trend of Disease Constitution of Hospitalized Neonates from 2004 to 2008 / 实用儿科临床杂志

Objective To analyze the trend of disease constitution of hospitalized neonates in China-Japan Friendship Hospital and provide a scientific basis for the focus adjustment of perinatal health.Methods Six hundred and ninety-eight neonates were admitted during Jan.2004 to Dec.2008.Relevant data of all cases were retrospectively collected.The discharge diagnosis of the neonates was counted accor-ding to the year,and the trends of the neonatal disease constitution of the 5 years were analyzed.Results 1.The first 10 diseases of hospita-lized neonates were centralized,and the first 3 diseases including premature infants,neonatal hypoxic-ischemic encephalopathy(HIE) and neonatal hyperbilirubinemia accounted for 42.84% of the neonate diseases.2.The characteristics of neonatal disease constitution were as fo-llows:the disease constitution of premature infants always located within the first 3 diseases;the location of neonatal HIE went ahead from number 8 to number 1 or 2,and its constitution proportion increased from 4.93% to more than 15.00%(P