scholarly journals Clinical and mutational spectrum of 4 Chinese families with glutaric aciduria type 1

2019 ◽  
Author(s):  
Xiaorong Shi ◽  
Qiaoyan Shao ◽  
Aidong Zheng ◽  
Wenghuang Xie
Keyword(s):  
Mutational Analysis ◽  
Southern China ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Glutaric Aciduria Type ◽  
Chinese Patients ◽  
Type I ◽  
Glutaric Aciduria Type 1 ◽  
Glutaric Aciduria ◽  
Molecular Aspects

Abstract Background To investigate clinical presentation and molecular aspects of five patients suffered from glutaric aciduria type I (GA-I ), a rare neurometabolic disorder caused by glutaryl-CoA dehydrogenase deficiency due to GCDH gene mutations. Methods All five patients were diagnosed by elevated urinary glutaric acid and GCDH gene analysis. Low protein diet supplemented with special formula, GABA analog and L-carnitine were initialed following laboratory confirmation of diagnosis. The clinical and biochemical features were analyzed, and mutational analysis of GCDH was conducted using Sanger sequencing. Results Clinical manifestations of 5 patients varied from macrocephaly to severe encephalopathy, with notably different phenotype between siblings with the same mutations. Three members present complex heterozygous mutations, while two sisters present homozygous mutations. Among them, four mutations in GCDH were identified (c.1133C>T 、c.1244-2A>C 、c.339delT 、c.406G>T). Of these four mutations, c.1244- 2A>C was found in four patients and c.339delT and c.1133C>T has not yet been reported until now. Conclusions In 5 Chinese patients with GA1, two novel mutations of GCDH gene were identified, which may expand the mutation spectrum of GCDH gene. What we found confirm that there is no correlation between clinical phenotype and genotype in GA-I patients, and c.1244-2A>C may be mutation hotspot in Southern China.

scholarly journals Clinical and Mutational Analysis of theGCDHGene in Malaysian Patients with Glutaric Aciduria Type 1

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Siti Aishah Abdul Wahab ◽  
Yusnita Yakob ◽  
Nor Azimah Abdul Azize ◽  
Zabedah Md Yunus ◽  
Leong Huey Yin ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Splice Site Mutation ◽  
Glutaric Aciduria Type ◽  
Missense Mutations ◽  
Site Mutation ◽  
Glutaric Aciduria Type 1 ◽  
Glutaric Aciduria ◽  
Dehydrogenase Enzyme ◽  
Molecular Aspects

Glutaric aciduria type 1 (GA1) is an autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase enzyme encoded by theGCDHgene. In this study, we presented the clinical and molecular findings of seven GA1 patients in Malaysia. All the patients were symptomatic from infancy and diagnosed clinically from large excretion of glutaric and 3-hydroxyglutaric acids. Bidirectional sequencing of theGCDHgene revealed ten mutations, three of which were novel (Gln76Pro, Glu131Val, and Gly390Trp). The spectrum of mutations included eight missense mutations, a nonsense mutation, and a splice site mutation. Two mutations (Gln76Pro and Arg386Gln) were homozygous in two patients with parental consanguinity. All mutations were predicted to be disease causing by MutationTaster2. In conclusion, this is the first report of both clinical and molecular aspects of GA1 in Malaysian patients. Despite the lack of genotype and phenotype correlation, early diagnosis and timely treatment remained the most important determinant of patient outcome.

Detection of inborn errors of metabolism using GC-MS: over 3 years of experience in southern China

2015 ◽  
Vol 28 (3-4) ◽  
Author(s):  
MinYan Jiang ◽  
Li Liu ◽  
HuiFen Mei ◽  
XiuZhen Li ◽  
Jing Cheng ◽  
...  
Keyword(s):  
Amino Acid ◽  
Inborn Errors Of Metabolism ◽  
Dehydrogenase Deficiency ◽  
Southern China ◽  
Glutaric Aciduria Type ◽  
Type I ◽  
Peroxisomal Disorders ◽  
Inborn Errors ◽  
Glutaric Aciduria ◽  
Chain Acyl

AbstractInborn errors of metabolism (IEM) have been detected worldwide using gas chromatography mass spectrometry (GC-MS) since the 1980s, but few related reports exist on the incidence, spectrum, and clinical presentation features of IEM in southern China.From January 2009 to March 2012, 16,075 urine samples were collected from patients who were highly suspected of having IEM in Guangzhou Women and Children’s Medical Center. The specimens were evaluated using GC-MS.We diagnosed 303 cases of IEM by urine GC-MS analysis, including 197 cases with amino acid disorders, 86 cases with organic acidurias (OAs), 10 cases with fatty acid oxidative (FAO) disorders, and 10 cases with peroxisomal disorders. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) was the most common (153 cases), followed by methylmalonic aciduria (48 cases), urea cycle disorders (21 cases), phenylketonuria (20 cases), propionic aciduria (11 cases), X-linked adrenoleukodystrophy (10 cases), multiple carboxylase deficiency (8 cases), glutaric aciduria type I (7 cases), isovaleric aciduria (6 cases), glutaric aciduria type II (4 cases), short-chain acyl-CoA dehydrogenase deficiency (4 cases), 3-hydroxy-3-methylglutaric aciduria (3 cases), maple syrup urine disease (2 cases), very long-chain acyl-CoA dehydrogenase deficiency (1 case), malonic aciduria (1 case), mevalonic aciduria (1 case), Canavan disease (1 case), lysine protein intolerance (1 case), and medium-chain acyl-CoA dehydrogenase deficiency (1 case). The clinical and laboratory features of IEM are neurologic signs, jaundice, metabolic acidosis, ketotic hypoglycemia, and hyperammonemia.In our study, GC-MS provided a diagnostic clue to OAs, amino acid disorders, FAO, and peroxisomal disorders. Urease pretreatment is useful for the diagnosis of NICCD. In southern China, the majority of IEM were amino acid disorders and organic acid disorders. FAO disorders were relatively rare, which we need to investigate further.

Clinical and molecular investigation in Chinese patients with glutaric aciduria type I

2016 ◽  
Vol 453 ◽  
pp. 75-79 ◽  
Author(s):  
Yanghui Zhang ◽  
Haoxian Li ◽  
Ruiyu Ma ◽  
Libin Mei ◽  
Xianda Wei ◽  
...  
Keyword(s):  
Glutaric Aciduria Type ◽  
Chinese Patients ◽  
Type I ◽  
Glutaric Aciduria ◽  
Glutaric Aciduria Type I ◽  
Molecular Investigation

scholarly journals Glutaric aciduria type 1 in children. Clinical presentation of 46 cases in Russian families

2021 ◽  
Vol 11 (2) ◽  
pp. 61-79
Author(s):  
S. V. Mikhailova ◽  
E. V. Saifullina ◽  
P. V. Baranova ◽  
V. P. Vorontsova ◽  
D.  I. Gribov ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Symptom Relief ◽  
Clinical Manifestations ◽  
Glutaric Aciduria Type ◽  
Chromosomal Microarray ◽  
Chromosomal Microarray Analysis ◽  
Disease Manifestation ◽  
Glutaric Aciduria Type 1 ◽  
Glutaric Aciduria

Background. Glutaric aciduria type 1 is an autosomal recessive disease caused by mutations in the GCDH gene, which encodes the enzyme glutaryl‑CoA dehydrogenase. Metabolic crisis in type 1 glutaric aciduria is an acute life‑threatening condition that requires careful diagnosis with a number of other conditions and the immediate initiation of pathogenetic therapy.Materials and methods. Clinical manifestations, neuroimaging characteristics of the disease were studied in 46 patients with diagnosed glutaric aciduria type 1 confirmed by biochemical and molecular genetic methods. Methods: gas chromatography with mass spectrometry, tandem mass spectrometry, Sanger sequencing, chromosomal microarray analysis of the exon level.Results and discussion. A retrospective analysis of anamnestic and clinical data was carried out, and the nature and age of disease manifestation, provoking factors, a spectrum of clinical manifestations and neuroimaging data were assessed.Conclusion. How initiated treatment prevents progression of neurological symptom relief and patient adaptation. With the help of the goal, it is necessary to inform pediatricians, neurologists and neuroradiologists about this feature of the course of glutaric aciduria type 1 in order to increase the clinical alertness of this disease.

Clinical and mutational spectra of 23 Chinese patients with glutaric aciduria type 1

2014 ◽  
Vol 36 (9) ◽  
pp. 813-822 ◽  
Author(s):  
Qiao Wang ◽  
Xiyuan Li ◽  
Yuan Ding ◽  
Yupeng Liu ◽  
Jinqing Song ◽  
...  
Keyword(s):  
Glutaric Aciduria Type ◽  
Chinese Patients ◽  
Glutaric Aciduria Type 1 ◽  
Glutaric Aciduria ◽  
Mutational Spectra

Hand tremor and orofacial dyskinesia: Clinical manifestations of glutaric aciduria type I in a young girl

2003 ◽  
Vol 18 (9) ◽  
pp. 1076-1079 ◽  
Author(s):  
Emilio Fernández-Álvarez ◽  
Angeles García-Cazorla ◽  
Anna Sans ◽  
Cristina Boix ◽  
María Antonia Vilaseca ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Glutaric Aciduria Type ◽  
Young Girl ◽  
Type I ◽  
Orofacial Dyskinesia ◽  
Hand Tremor ◽  
Glutaric Aciduria ◽  
Glutaric Aciduria Type I

scholarly journals Evaluation of the Clinical, Biochemical, Neurological, and Genetic Presentations of Glutaric Aciduria Type 1 in Patients From China

2021 ◽  
Vol 12 ◽  
Author(s):  
Huishu E. ◽  
Lili Liang ◽  
Huiwen Zhang ◽  
Wenjuan Qiu ◽  
Jun Ye ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Screening Program ◽  
Brain Mri ◽  
Clinical Intervention ◽  
Glutaric Aciduria Type ◽  
Chinese Patients ◽  
Common Symptom ◽  
Glutaric Aciduria Type 1 ◽  
Glutaric Aciduria

PurposeTo characterize the phenotypic and genotypic variations associated with Glutaric aciduria type 1 (GA1) in Chinese patients.MethodsWe analyzed the clinical, neuroradiological, biochemical, and genetic information from 101 GA1 patients in mainland China.Results20 patients were diagnosed by newborn screening and the remaining 81 cases were identified following clinical intervention. Macrocephaly was the most common presentation, followed by movement disorders and seizures. A total of 59 patients were evaluated by brain MRI and 58 patients presented with abnormalities, with widening of the sylvian fissures being the most common symptom. The concentration of glutarylcarnitine in the blood, glutarylcarnitine/capryloylcarnitine ratio, and urine levels of glutaric acid were increased in GA1 patients and were shown to decrease following intervention. A total of 88 patient samples were available for genotyping and 74 variants within the GCDH gene, including 23 novel variants, were identified. The most common variant was c.1244-2A > C (18.4%) and there were no significant differences in the biochemical or clinical phenotypes described for patients with the four most common variants: c.1244-2A > C, c.1064G > A, c.533G > A, and c.1147C > T. Patients identified by newborn screening had better outcomes than clinical patients.ConclusionOur findings expand the spectrum of phenotypes and genotypes for GA1 in Chinese populations and suggest that an expanded newborn screening program using tandem mass spectrometry may facilitate the early diagnosis and treatment of this disease, improving clinical outcomes for patients in China.

scholarly journals A Case of Mistaken Identity: Glutaric Aciduria Type I Masquerading as Postmeningitic Hydrocephalus

2018 ◽  
Vol 8 ◽  
pp. 50
Author(s):  
Heena Rajani ◽  
Shabnam Bhandari Grover ◽  
Neha Antil ◽  
Amit Katyan
Keyword(s):  
Neurological Diseases ◽  
Glutaric Aciduria Type ◽  
Periventricular White Matter ◽  
Type I ◽  
Imaging Features ◽  
Glutaric Aciduria Type 1 ◽  
Glutaric Aciduria ◽  
Mistaken Identity ◽  
Diffuse Brain

We report the characteristic neuroimaging features of a rare metabolic leukodystrophy in an 8-year-old boy, born of consanguineous parenthood. The child presented with macrocrania, regression of milestones, and dystonia. The patient was referred for magnetic resonance imaging with a clinical diagnosis of postmeningitic hydrocephalus. Imaging revealed ventriculomegaly, diffuse brain atrophy, bilaterally symmetric widened sylvian fissure with temporal lobe hypoplasia, periventricular white-matter hyperintensities, and atrophy with hyperintensity in bilateral basal ganglia was also seen. These imaging features were signatory to arrive at a diagnosis of glutaric aciduria type 1. This disorder may mimic other neurological diseases such as postmeningitic hydrocephalus, which delays the diagnosis. Since early diagnosis and treatment can arrest progression, increased awareness about this condition among radiologists will certainly prevent erroneous diagnosis as had occurred in our patient.

scholarly journals A rare case of type i glutaric aciduria in an early child

2020 ◽  
Vol 11 (4) ◽  
pp. 84-91
Author(s):  
A. A. Lebedenko ◽  
S. B. Berezhanskay ◽  
A. S. Todorova ◽  
N. N. Vostrykh ◽  
E. Y. Kaushanskay ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Late Onset ◽  
Clinical Manifestations ◽  
Glutaric Aciduria Type ◽  
Organic Aciduria ◽  
Type I ◽  
Gene Encoding ◽  
Glutaric Aciduria ◽  
Phenotypic Spectrum ◽  
Rare Autosomal Recessive Disease

Glutaric aciduria type I (deficiency of glutaryl-COA dehydrogenase, glutaric acidemia type I) is a rare autosomal recessive disease caused by mutations in the gene encoding the enzyme glutaryl – COA - dehydrogenase (GCDH). Cerebral organic aciduria, caused by a deficiency of glutaryl-COA - dehydrogenase, is generally considered a neurological disorder.The phenotypic spectrum of untreated GA-1 varies from a more common and pronounced form (a disease with infancy) to a low-symptom and less common form. In people with the same genotype, the clinical manifestations and depth of CNS damage can vary widely depending on the age of manifestation of acute encephalopathic crises. It is assumed that with early detection and treatment of “asymptomatic” newborns (in the context of screening for this disease), most people who would have developed manifestations of GA-1 with childhood or late onset will remain asymptomatic. 

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