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Gaucher′s disease (GD) is a lysosomal storage disease, and the etiology of GD is the decreased activity of glucocerebrosidase, which leads to the accumulation of glucocerebroside in the lysosomes of macrophages. Because GD is rare and lacks specific clinical manifestations, it is easy to be misdiagnosed, which delays the best time for treatment. Early diagnosis, clinical evaluation, and regular monitoring of the disease have important clinical significance for enzyme replacement therapy in patients with GD. Recent studies have found that radionuclide imaging is playing an increasingly important role in the diagnosis and treatment of GD. This article introduces the application of radionuclide imaging in the diagnosis and management of GD.
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Objective:To summarizes the diet management of one child with GSD I and severe hyperlipidemia.Methods:Key points of diet management include: making an individual diet plan, correcting parents' dietary misunderstanding, adjusting dietary and keeping following up regularly and keeping a food diary.Results:Following up for 11 months, the children basically formed a stable diet pattern, the blood glucose level was basically maintained between 4~6 mmol/L, the indicators of hyperlipidemia, hyperlactic acid and liver function were significantly improved compared with the previous period, and the height increase was guaranteed, while the weight gain was effectively controlled.Conclusions:It shows that individualized dietary guidance has a significant effect on the maintenance of blood glucose level, improvement of growth and development status and metabolic control in children with GSD I.
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A 44-year-old pregnant woman (G5P3) who had delivered two children with DMD was admitted and underwent prenatal diagnosis at Peking Union Medical College Hospital in 2019. (1) The karyotype of the fetus in 2019 was 47,XXY. The fluorescence in situ hybridization (FISH) result showed a nucish(CSPX×2, CSPY×1)[100] and multiplex ligation-dependent probe amplification (MLPA) suggested sex chromosome abnormality. Based on the above results, the fetus was diagnosed with Klinefelter syndrome. Fetal short tandem repeat (STR) linkage analysis and Sanger sequencing indicated a heterozygous mutation of c.9543delG(p.Trp3181CysfsTer2). (2) Sanger sequencing of the proband found a novel frameshift mutation of c.9543delG(p.Trp3181CysfsTer2 ) in exon 65 of the DMD gene. (3) The male fetus performing prenatal diagnosis in 2008 was found to have the same maternal gene markers as the proband with the same genotype. While the genotype of the fetus in 2009 obtained a different maternal gene marker from the proband and did not detect the same DMD gene mutation. This fetus was delivered at full term and was good during follow-up. (4) The elder brother and cousin of the proband had the same frameshift mutation in exon 65 of the DMD gene as the proband. The mother of the proband was a heterozygous carrier of the mutation.
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Objective To analyze the clinical features of secondary gout in glycogen storage disease type Ⅰ a (GSD Ⅰ a),so as to improve the awareness of this disease.Methods The clinical features,laboratory findings,treatments and prognosis of 5 GSD Ⅰ a patients with secondary gout who had been admitted to the Peking Union Medical College Hospital during 2006 to 2016 were collected and analyzed.GSD Ⅰ a was confirmed by liver biopsy and genotyping.Results Among the 5 patients (median age:27 years),3 were males and 2 were females.The mean age of gout onset was 17 ranging from 10 to 22 years old.The common manifestations of GSD included hepatomegaly since childhood,hypoglycemia,growth retardation,anemia,hyperlactacidemia and hyperlipidemia.All the 5 patients were complicated with gouty tophi and kidney stone.Gouty tophi and kidney stone were identified 3.8 years and 10.2 years after the first occurrence of articular symptoms,respectively.Renal damage occurred in 3 cases.All the patients underwent several therapeutic modalities including lifestyle intervention,allopurinol,and raw corn starch treatment.Conclusions Determination of the presence of primary disease should be performed actively for young-onset gout with early occurrence of gouty tophi.GSD should be suspected if there exist clinical manifestations like hepatomegaly,recurrent hypoglycemia,growth retardation.Early management of hyperuricemia and gout in GSD patients is important to prevent complications and improve prognosis.
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The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.
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Objective To explore the clinical and genetic characteristics of congenital generalized lipodystrophy (CGL). Method The clinical data of one child with CGL caused by BSCL2 gene mutation were analyzed retrospectively and relative literature were reviewed. Results A 2-year-9-month old girl had clinical manifestations of a lack of subcutaneous fat, acanthosis nigricans, hepatolienomegaly and mild hypophrenia. Laboratory examinations showed hypertriglyceridemia, hyperinsulinemia and cardiomyopathy. The peripheral blood from the child and her parents were collected and 4 genes, AGPAT2, BSCL2, CAV1 and PTRF, were sequenced by Sanger. The results showed a heterozygous mutation of BSCL2 gene from maternal frameshift (c.567-568delGA, p.E189EfsX12) and paternal nonsense mutation (c.565G>T,p.E189X) respectively in the child, and both mutations were pathogenic ones. By a literature review, it is known that BSCL2 gene mutation is the most common cause of in Asian. In CGL with BSCL2 gene mutation, the commom clinical manifestations include disappearance of systemic adipose tissue, acathosis nigricans and hepatomegaly, and the incidence of myocardial infarction and mental retardation were 40% and 30% respectively. Conclusion The main clinical manifestations of CGL caused by BSCL2 gene mutation were loss of systemic adipose tissue and metabolic disorder at an early age. It was often accompanied by myocardial lesions and mental retardation. Gene diagnosis analysis should be made as earliest possible time for the children suspected of this disease.
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Objective To investigate the biochemical disturbances,nutritional assessment and nutritional interventions in hospitalized patients with glycogen storage disease (GSD) in a general hospital in Beijing and provide examples of advanced nutritional management for these patients.Methods We retrospectively reviewed 22 consecutive hospitalized patients with GSD diagnosed from January 1,2013 to January 1,2016 in Peking Union Medical College Hospital and analyzed their medical data,nutritional assessments,and interventions.Results These 22 GSD patients included 2 cases with GSD-Ⅰa,3 cases with GSD-Ⅰb,and 17 cases with GSD-Ⅲ.They were composed of 21 children (including a 6-month old infant and a 7-month old infant) and one 18-yearold man.Biochemical abnormalities:hypoglycemia (5/5),hyperlactacidemia (4/5),hyperlipidemia (4/5),hyperuricemia (4/5) were common in GSD-Ⅰ patients,while hypoglycemia (17/17),hyperlactacidemia (5/17),hyperlipidemia (7/17),and hyperuricemia (3/17) were also present among patients with GSD-Ⅲ.Growth and development assessments:among 5 patients with GSD-Ⅰ,the body weight was below the 10th percentile in of 4 patients and the height was below the 3rd percentile in 5 patients;among 17 patients with GSD-Ⅲ,the body weight was below the 10th percentile in 4 patients and the height was below the 10th percentile in 9 patients.Nutritional management condition:all the patients received nutritional assessment,dietary modulation and nutritional support.Twenty children or adolescents were prescribed with raw corn starch (RCS) every 4-6 hours,with a mean initial dose of (1.58±0.28) g and (1.21±0.33) g for patients with GSD-Ⅰ and GSD-Ⅲ,respectively;the other 2 infant aged 6-month old and 7-month old were regularly administered amino acid-based enteral nutritional agents.In addition,all the patients with GSD-Ⅲ were recommended high protein intake of 3 g/(kg · d) and received dietary guidance and modulation.Follow-up condition:5 cases with GSD-Ⅰ and 2 cases with GSD-Ⅲ stayed in track after discharge from our hospital.The mean follow-up duration was (480.40±246.16) d and (373.00± 108.89) d for patients with GSD-Ⅰ and GSD-Ⅲ,respectively.All the patients reported alleviated symptom of hypoglycemia,and the examinations also indicated improved fasting blood glucose,uric acid,lipid profile,and growth status.Conelusions Hypoglycemia,metabolic disturbances,and growth retardation are prevalent in both GSD-Ⅰ and GSD-Ⅲ patients.Potential biochemical abnormalities should not be ignored in GSD-Ⅲ patients,especially in young patients.Comprehensive nutrition assessment,regular administration of RCS,sufficient protein intake,and continuous patient follow-up and surveillance can help to alleviate symptoms,correct metabolic disturbances,and improve growth status of patients with GSD.
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Objectives To analyze SLC37A4 gene mutations in glycogen storage disease type Ⅰb patients and to investigate the correlation between genotype and phenotype. Methods The clinical data and SLC37A4 gene detection results of 3 cases of glycogen storage disease type Ⅰb were analyzed retrospectively. Results Two males and one female aged 6 years, 9 years, and 16 years respectively were presented with hepatomegaly, fasting hypoglycemia, slactic academia, hyperlipidemia, and granulocytopenia. The analysis of 6 alleles in SLC37A4 gene by direct sequencing of peripheral blood DNA found 4 mutations, including 2 missense mutation (p. Leu23Arg and p.Pro191Leu), one shear mutation (c.870+5G>A), and one deletion mutation (c.1042_1043 del CT). The genotypes of these 3 cases were p.Pro191Leu, p.Pro191Leu;p. Leu23Arg, c.870+5G>A;p.Pro191Leu, p.Leu347ValfsX53 respectively. Conclusions There were 4 mutations detected among these 3 cases of glycogen storage disease type Ⅰb. All of those were known mutations. The most common mutation was p.Pro191Leu. It can not be excluded that P.Gly149Glu homozygous mutation is associated with repeated infections.
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Objective To analyze and summarize the clinical characteristics of patients with spontaneous hemor -rhage of hepatic adenoma in glycogen storage disease type Ⅰa.Methods Reporting 1 case in our hospital and making a summary about general situation , category, etiology, diagnosis and treatment of the hemorrhage of hepatic adenoma with glycogen storage disease type Ⅰa through checking literatures .Results The patient was a 27 year old male who had been diagnosed as glycogen storage disease for 14 years, as well as was first found hepatic adeno-ma at the age of 17 .He once was diagnosed as intra-adenoma bleeding with persistent abdominal pain and dizziness and was underwent selective hepatic artery embolization at the age of 22.Hepatic adenoma in glycogen storage dis-ease typeⅠa generally appeared at the age of puberty .One common complication of this disease was hemorrhage of hepatic adenoma , which can be found by ultrasonography and CT .Clinical management includs observation , selec-tive hepatic artery embolization , radiofrequency ablation , surgical resection and liver transplantation .Conclusions Glycogen storage disease type Ⅰa is an autosomal recessive genetic disease with hepatic adenoma as a common complication of GSD Ⅰa, serious liver adenoma's hemorrhage can be life threatening , the radiological examination can be helpful to detect hepatic adenoma .Then appropriate intervention can improve the life quality and prognosis .
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<p><b>OBJECTIVE</b>Schimke immuno-osseous dysplasia (SIOD), is an autosomal recessive inherited disease caused by SMARCAL1 (MIM:20606622) mutations, while in about half of the patients no any mutation in SMARCAL1 could be found. This disease involves multiple systems and is characterized by short and dissymmetric stature with spondyloepiphyseal dysplasia, progressive renal failure, lymphopenia with recurrent infections, and hyperpigmented macules. This study aimed to analyze SMARCAL1 gene of 2 unrelated suspected SIOD children, to make definite diagnosis, and find more SMARCAL1 mutation types of Chinese SIOD.</p><p><b>METHOD</b>Two suspected Chinese Han male SIOD children who visited our hospital from 2008 to 2014, aged 3 y 6 m and 7 y 8 m, both were short and had spondyloepiphyseal dysplasia, progressive renal failure, lymphopenia with recurrent infections. After informed consent, they and their parents's DNA were extracted from blood. PCRs for all 16 exons of SMARCAL1 were performed and PCR products were purified by 2% gel electrophoresis and sequenced directly. Pathogenicity of missense variations was confirmed by SIFT and sequencing SMARCAL1 of fifty normal controls.</p><p><b>RESULT</b>(1) Four gene variations were found in the two children: Two reported missense mutations c.1129G>C, p.Glu377Gln and c.1933C>T, p. Arg645Cys. Two splicing mutations c.1334+1G>A and c.2142-1 G>A were detected. (2) c.1129G>C, p.Glu377Gln were reported as a disease-causing mutations before, but it was an single nucleotide polymorphism (SNP) which was found in 15 of 50 normal controls. (3) Two novel splicing mutations were found in this study: c.1334+1G>A and c.2142-1 G>A.</p><p><b>CONCLUSION</b>(1) We detected 3 disease-causing mutations in 2 SIOD children by SMARCAL1 gene analysis, while 2 splicing mutations were novel mutations. (2) c.1129G>C, p.Glu377Gln was a SNP but not a disease-causing mutation at least in Chinese population.</p>
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Niño , Preescolar , Humanos , Masculino , Arteriosclerosis , Genética , Secuencia de Bases , ADN Helicasas , Genética , Exones , Síndromes de Inmunodeficiencia , Genética , Linfopenia , Mutación , Mutación Missense , Síndrome Nefrótico , Genética , Osteocondrodisplasias , Genética , Polimorfismo de Nucleótido Simple , Embolia Pulmonar , Genética , Insuficiencia RenalRESUMEN
<p><b>OBJECTIVE</b>To investigate the clinical and genetic features of 2 patients with Rubinstein-Taybi syndrome.</p><p><b>METHOD</b>Using next generation sequencing (NGS) the CREBBP and EP300 genes of 2 children who were diagnosed as Rubinstein-Taybi syndrome at Peking Union Medical College Hospital. The mutations identified by NGS were verified by PCR were analyzed.</p><p><b>RESULT</b>The 2 patients at the age of 5 months and 4.5 years manifested short stature (the height were 60 cm and 99 cm respectively), low hairline, thick and dense hair and eyebrows, long lash, epicanthus of both eyes, protruded supercilliary arch, broad and flat thumbs and halluces, and particular facial abnormalities. Patient 2 had language retardation besides. One missense mutation of c.3535A>G, p.Ser1179Gly was found in CREBBP gene in patient 1 and one microdeletion mutation of c.4995_4999delCGCCT, p. Ala1666Pro fs66x was found inpatient 2. Both mutations were reported for the first time.</p><p><b>CONCLUSION</b>Rubinstein-Taybi syndrome is characterized by mental and growth retardation, wide and flat thumbs and first toes, and dysmorphic facial features. CREBBP is one of the causative genes. Mutation detection on CREBBP gene can confirm the diagnosis of Rubinstein-Taybi syndrome.</p>
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Niño , Humanos , Masculino , Proteína de Unión a CREB , Genética , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Genética , Mutación Missense , Síndrome de Rubinstein-Taybi , Diagnóstico , GenéticaRESUMEN
<p><b>OBJECTIVE</b>Blau syndrome (BS), an autosomal dominant inherited autoinflammatory disease, is caused by NOD2 mutations. This study aimed to analyze NOD2 gene of suspected BS patients to make definite diagnosis, find NOD2 mutation types and clinical features of Chinese BS cases, and find some clinical indications to identify BS by comparing BS and non-BS cases.</p><p><b>METHOD</b>Eighteen suspected BS children (7 boys and 11 girls, age of first visit was from 1 y 8 m to 9 y 6 m) who visited Peking Union Medical College Hospital from 2006 to 2014 and their parents's DNA were extracted from 4 ml blood specimens. PCR was performed for exon 4 of NOD2 and PCR products were purified by 2% gel electrophoresis and sequenced directly. Role of novel missense mutations in pathogenicity was analyzed by SIFT and sequencing NOD 2 of fifty normal controls. Clinical data of BS children diagnosed by NOD2 analysis were summarized and compared with the data of non-BS group.</p><p><b>RESULT</b>(1) Twelve of eighteen suspected BS children were diagnosed as BS by NOD2 analysis, and the remaining 6 were excluded. Seven missense mutations were detected, 4 were reported before: c.1000C>T, p. Arg 334Trp; c.1001G>A, p. Arg334Gln; c.1538T>C, p. Met513Thr; c.1759C>T, p. Arg587Cys. Three novel mutations were found: c. 1147 G>C, p.Glu383Gln; c.1471A>T, p. Met491Leu; c.2006A>G, p.His669Arg. (2) Chronic symmetric arthritis and multi-joints periarticular hydatoncus, which were painless with fluctuation, were found in all 12 BS children with NOD2 mutations. Skin rash, chronic symmetric arthritis, and recurrent uveitis were identified in 7 patients. Three patients had no skin rash, while 1 had no uveitis, 1 only had symmetric arthritis and multi-joints periarticular hydatoncus. Four children inherited the disease from father. (3) Compared with other 6 non-BS children, BS children had such different clinical characteristic (P < 0.05): All the BS cases had multiple periarticular hydatoncus, which always had no persistent fever, most had no elevated CRP, while non-BS group always had no hydatoncus, most had persistent fever, all had elevated CRP.</p><p><b>CONCLUSION</b>The 12 BS children were diagnosed by NOD2 analysis; 7 missense mutations were detected, 3 were novel mutations, adding new findings to human NOD2 mutations. Although classic BS was characterized by skin rash, arthritis, and eye involvement, some presented with less than 3 of the classic features. Chronic symmetric arthritis and multi-joints periarticular hydatoncus were the most comment fetures. Comparing with non-BS group, all BS cases had multi hydatoncus surrounding multi-joints, always had no persistent fever, most had no elevated CRP. Those features may distinguish BS in clinical settings.</p>
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Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Artritis , Pueblo Asiatico , Genética , Secuencia de Bases , Estudios de Casos y Controles , Enfermedades de los Nervios Craneales , Genética , Exantema , Exones , Genética , Mutación , Genética , Mutación Missense , Proteína Adaptadora de Señalización NOD2 , Genética , Sinovitis , Genética , Uveítis , GenéticaRESUMEN
A neonatal girl with overextended knees admitted to NICU of our hospital was diagnosed as cri du chat (cat cry) syndrome.We collected 34 cases of cri du chat reported in journals since 2000,the clinical features of total 35 cases were retrospectively analyzed.Among 35 cases 12 were boys and 23 girls.The most common clinical manifestations were characteristic face features(100％),difficult feeding(100％) and typical sound of cry(94％).The main complains at hospital visit were typical cry,difficult feeding and cyanosis in the neonatal period,while in childhood period were recurrent respiratory infection,developmental retardation and other abnormalities.Most cases were diagnosed in the neonatal phase,while 85.3％ were in the first year.The diagnosis was based on karyotype analysis; chromosome 5 short arm deletion (5P-) was the most significant genetic variation and clinical features were associated with the position of deletion.
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Objective To report a case of progressive pseudorheumatoid dysplasia (PPD) with two kinds of WISP3 gene mutation. Methods A case of PPD was reported. Its clinical profile and the process of diagnosis were analyzed, and the related literature were reviewed. Results A 15-years old boy, who developed progressive joint pain and enlargement with spine involvement, was diagnosed as PPD. The erythrocyte sedimentation rate and C-reactive protein were in normal range, rheumatoid factor and anti-CCP antibody were all negative. HLA-B27 was also negative. Gene study discovered two kinds of mutations in Wnt1-inducible signaling pathway protein 3 (WISP3) gene: c.589+2T＞C and c.624dupA. Radiographic studies revealed severe osteoporosis without erosion, platyspondylia, enlargement of metaphysis and scoliosis deformity. The joint space of sacroiliac joint and articulation of pubis were significantly widened. Conclusion PPD is a rare autosomal recessive disorder characterized by cartilage homeostasis. It is associated with WISP3 gene mutations. Gene detection, laboratory examination and typical radiographic features are helpful for the diagnosis. This is the first report of c.589+2T＞C and c.624dupA mutations in patients with PPD in our country.
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Objective To summarize and analyze clinical characteristics of glycogen storage disease (GSD)typeⅠcomplicated with hepatocellular carcinoma to improve clinical recognition to it.Methods First case of GSD type Ia complicated with hepatocellular carcinoma(HCC)in China was reported and another 14 cases with detailed clinical data reported in literatures were reviewed in this paper.Results The case was man at age of 19 with chief complaint of hepatic mass founded casually.For all the 15 cases(other 14 from literature reports),mean age at diagnosis of HCC was 32.3 years and average time interval from diagnosis of GSD to diagnosis of HCC Was 23.1 years,as compared to 23.3 years and 14.6 years,respectively in three cases with both hepatitis B virus(HBV)and hepatitis C virus(HCV)seropositive.Serum level of alpha fetoprotein(AFP)was elevated in six patients.Tumor could be located at all lobes of the liver and mainly in the right lobe(eight of 15 cases),with varied size and solitary or multiple tumor.Conclusions Symptoms in GSD typeⅠcomplicated with HCC Was latent at onset.and AFP measurement was questionable in its diagnosis.It is important that physicians should keep more alert to risk of HCC in patients with GSD for its early diagnosis.
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Objective To study renal involvement in hepatic glycogen storage disease(GSD) in childhood. Methods One hundred and eight patients aged less than 21 years old with type Ⅰa GSD (54 cases), type Ⅲ (29 cases) and uncertain type hepatic GSD (25 cases). Urine analysis, urine albumin, urine protein of 24 h, urine ?_2-MG, BUN, creatinine, Ccr were evaluated. Results Of 108 patients with hepatic GSD, 16 patients (20.8%) had proteinuria proven by urine albumin or urine protein of 24 h, their ages first found proteinuria were 8～15 years. Two 15-year-old patients had proteinuria over 1.0g/24h. Among 72 patients, urine ?_2-MG of 51 cases (70.8%) increased (175～10 623mg/L), and the mean urine ?_2-MG of type Ⅰ a GSD was much higher than that of type Ⅲ GSD, 4138.2 and 1790.1mg/L respectively. Of 91 patients, 10 had renal insufficiency, 1/10 (15-year-old girl) had heavy proteinuria (3.5g/24h), elevated BUN (9.3mmol/L) and Scr(1061 ?mol/L). Five elder patients (11～21 years old) had hematuria with renal colic caused by renal calculus. Conclusions Persistent protenuria, increased urine ?_2-MG, decreased Ccr, and renal stones are common complications of hepatic GSD in childhood. Renal function should be thoroughly evaluated during follow-up.