Hiperwarburgismo: la "hipoglucemia feliz" de los pacientes oncológicos: Revisión narrativa / Hyperwarburgism: the "Happy hypoglycemia" of cancer patients: Case report and review of literature

Introducción: La glucosa es el combustible energético cerebral, esta relación es establecida de manera integral en la inmensa mayoría de revisiones, debido al ávido consumo -y casi exclusivo - glucósico por parte del tejido neuronal. En esta esfera, la hipoglucemia se traduce por defecto en un conjunto de síntomas neurológicos, resultado del estado neuroglucopénico. Cuando la caída de estos niveles glicémicos es pronunciada desencadena alteraciones del estado sensorial, pudiendo llegar al coma con daños irreversibles de sostenerse en el tiempo. Propósito de la revisión: El objetivo de la revisión es presentar un caso de hipoglucemia severa sin sintomatología neuroglucopénica. Recientes hallazgos: Al ausencia de sintomatología neurológica se da debido al consumo del lactato ­ tradicionalmente producto anaerobiótico ­ como una vía metabólica energética alternativa al consumo de glucosa. La hipoglucemia puede ser compensada a nivel neurológico con sistemas lanzadores de lactato en el tejido neuronal, este puede sustituir a la glucosa como sustrato energético del cerebro. Conclusiones: La hipoglicemia sin síntomas adrenérgicos o neuroglucopénicos es un tema vinculado a pacientes oncológicos, y propone al lactato como combustible del tejido nervioso adicional a la glucosa. Por otra parte, la asociación lactato = hipoperfusión, es otra entidad que debe ser revisada y reanalizada por todo lo que implica el lactato dentro de la vía fisiopatológica metabólica corporal.

Introduction: Glucose is the cerebral energy fuel; this relationship is fully established in most re-views due to neuronal tissue's avid and almost exclusive glucose consumption. In this sphere, hypoglycemia is translated by default into a set of neurological symptoms resulting from the neuroglycopenic state. When the drop in these glycemic levels is pronounced, it triggers alterations in the sensory state, being able to reach a coma with irreversible damage if sustained over time. Purpose of the review: The objective is to present a case of severe hypoglycemia without neu-roglycopenic symptoms. Recent findings: The absence of neurological symptoms is due to the consumption of lactate ­ traditionally an anaerobic product ­ as an alternative energy metabolic pathway to glucosa consumption. Hypoglycemia can be compensated at the neurological level with lactate launching systems in neuronal tissue, replacing glucose as the brain's energy substrate. Conclusions: Hypoglycemia without adrenergic or neuroglycopenic symptoms is an issue linked to cancer patients, and lactate is proposed as fuel for nervous tissue in addition to glucose. On the other hand, the lactate-hypoperfusion association is another entity that must be reviewed and reanalyzed for everything that lactate implies within the body's metabolic pathophysiological pathway.

Analysis of GCDH gene variant in a child with Glutaric aciduria type I / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a neonate affected with Glutaric aciduria type I (GA-I).@*METHODS@#Targeted capture and high-throughput sequencing was carried out for the proband and her parents. Candidate variants were verified by Sanger sequencing.@*RESULTS@#The proband was found to harbor compound heterozygous variants of the GCDH gene, namely c.523G>A and c.1190T>C, which was derived from her father and mother, respectively.@*CONCLUSION@#The compound heterozygous variants of the GCDH gene probably underlay the GA-I in the patient.

Aciduria L-2-hidroxiglutárica. A propósito de un caso / L-2-hydroxyglutaric aciduria. A case report

L-2-hydroxyglutaric aciduria (AL2HG) is a rare autosomal recessive neurometabolic disorder. It is characterized by elevated of L-2-hydroxyglutarate and lysine in urine, cerebrospinal fluid and plasma. Patients usually have neurological manifestations including mild to moderate psychomotor developmental delay, cerebellar ataxia, macrocephaly and epilepsy. Magnetic resonance imaging (MRI) has shown abnormalities in the signal intensity of the subcortical cerebral white matter, putamen and dentate nucleus. This article reports a case to demonstrate the classically described imaging findings.

La aciduria L-2-hidroxiglutárica (AL2HG) es un raro trastorno neurometabólico de tipo autosómico recesivo. Se caracteriza por niveles elevados de L-2-hidroxiglutarato y lisina en orina, líquido cefalorraquídeo y plasma. Los pacientes suelen tener manifestaciones neurológicas que incluyen retraso en el desarrollo psicomotor de leve a moderado, ataxia cerebelosa, macrocefalia y epilepsia. En resonancia magnética (RM) se han descrito anormalidades en la intensidad de señal de la sustancia blanca cerebral subcortical, el putamen y el núcleo dentado. En este artículo se presenta un caso para demostrar los hallazgos por imagen que se describen clásicamente.

¿Encefalopatía o encefalitis por varicela-zóster? Una paciente con una punción lumbar engañosa / ENCEPHALOPATHY OR VARICELLA-ZOSTER ENCEPHALITIS? A PATIENT WITH A TRICKY LUMBAR PUNCTURE

La encefalopatía es un cuadro clínico característico de múltiples procesos neurológicos y sistémicos que no hay que confundir con la encefalitis, que es una inflamación cerebral, normalmente causadas por infecciones virales. Se presenta el caso de una mujer de 58 años con enfermedad renal crónica en diálisis peritoneal, que ingresa por sepsis de origen peritoneal con clínica de encefalopatía y crisis epilépticas parciales. La paciente presenta lesiones de herpes zóster en zona lumbar y se practica punción lumbar, con resultado del líquido cefalorraquídeo positivo para virus varicela-zóster, por lo que completa tratamiento con aciclovir. En la resonancia magnética no presenta ninguna alteración, y una segunda punción lumbar tras mejoría de las lesiones cutáneas es negativa. El curso de la paciente es fluctuante durante el ingreso, con mejoría significativa tras antibióticos, hemodiálisis y tratamiento antiepiléptico, y no respondiendo al aciclovir. La etiología sospechada es la debida al contexto infeccioso y metabólico de la paciente. Probablemente el resultado del líquido fue contaminado por la proximidad de las lesiones herpéticas, ya que además no es frecuente encontrar encefalitis infecciosas agudas sin alteraciones en las pruebas de imagen. La mejoría final fue debida tanto a la medicación antiepiléptica como al inicio de hemodiálisis

Encefalopathy is a clinical syndrome ocurring in multiple neurologic and systemic diseases which must not be mistaken with encephalitis, that is a cerebral inflammatory process, often caused by viral infections. We present the case of a 58-year-old woman with chronic renal failure receiving peritoneal dyalisis, who was admitted into hospital for sepsis secondary to infectious peritonitis, with encefalopathy and epileptic partial seizures. The patient presented lumbar herpetic cutaneous lesions and a lumbar punction is practiced, with a positive result in the cerebrospinal fluid for varicella-zoster virus. Treatment with aciclovir was completed. Her cerebral magnetic resonance was absolutely normal, and a second lumbar puncture when herpetic lesions got better was negative. The course is fluctuating during the stay, and a significant clinical improvement occurs after antibiotics, hemodyalisis and antiepileptic treatment. The patient did not respond to aciclovir. The suspected ethiology is the infectious and metabolic context. Positivity for the virus is thought to be a contamination from the nearby herpetic lesions. Also, it is rare for an infectious acute encephalitis to present with normal radiologic imaging. The final clinical improvement was probably due to hemodyalisis initiation and the antiepileptic treatment.

Analysis of CGDH gene variants and clinical features in three patients with glutaric aciduria type Ⅰ / 中华医学遗传学杂志

OBJECTIVE@#To screen for potential variants of GCDH gene in 3 patients clinically diagnosed as glutaric aciduria type Ⅰ.@*METHODS@#GCDH gene variants was detected by Sanger sequencing among the three children and their family members.@*RESULTS@#Sanger sequencing showed that patient 1 carried compound heterozygosity variants of c.532G>A (p.Gly178Arg) and c.655G>A (p.Ala219Thr) of the GCDH gene, while his father and mother respectively carried heterozygous c.532G>A(p.Gly178Arg) and c.655G>A (p.Ala219Thr) variants. Patient 2 carried c.532G>A (p.Gly178Arg) and a novel c.1060G>T (p.Gly354Cys) compound heterozygous variant, while his father and mother respectively carried heterozygous c.532G>A (p.Gly178Arg) and c.1060G>T (p.Gly354Cys) variant. Patient 3 carried homozygous c.532G>A (p.Gly178Arg) variant of the GCDH gene, for which both of his parents were heterozygous carriers.@*CONCLUSION@#The GCDH gene variant probably underlie the glutaric aciduria type Ⅰ among the 3 patients. Identifcation of the novel variant has enriched the spectrum of GCDH gene variants.

Clinical phenotype and novel mutation in one of twins with glutaric acidemia type I / 中华医学遗传学杂志

OBJECTIVE@#To review the clinical features of a male twin affected with glutaric academia type I (GA-I) and analyze the variations of glutaryl-CoA dehydrogenase (GCDH) gene.@*METHODS@#Clinical data of the pair of twins and their parents were collected. Genomic DNA was extracted from peripheral blood samples, and variants of GCDH genes were detected by capture sequencing using a customized panel. Variants of the twins and their parents were verified by Sanger sequencing.@*RESULTS@#The level of glutaric acyl carnitine (C5DC + C6OH) was 3.26 μmol/L in the male twin. The relative level of glutaric acid in urine was 547.51 by gas chromatography mass spectrometry analysis. Cerebral ultrasonography showed that the patient had subependymal hemorrhage, but no serious clinical manifestation was noted. After treating with special formula milk powder and L-carnitine, the boy showed good growth and development. Two heterozygous variants of the GCDH gene were detected in the patient, among which c.416C>G was suspected to be pathogenic, while c.109_110delCA was unreported. The variants were respectively inherited from his parents. The twin girl only carried the c.416C>G variant.@*CONCLUSION@#GA-I can be diagnosed by mass spectrometry, urine gas chromatographic mass spectrometry, imaging as well as genetic diagnosis. Early diagnosis and intervention is important.

Clinical and variation analysis of three Chinese families affected with glutaric acidemia type 1 / 中华医学遗传学杂志

OBJECTIVE@#To detect potential variation in glutaryl-CoA dehydrogenase (GCDH) gene among three Chinese families affected with glutaric acidemia type Ⅰ(GA-1) and correlate the genotypes with phenotypes.@*METHODS@#Genomic DNA was extracted from peripheral blood samples derived from three patients with GA-1 and their family members. The coding regions of the GCDH gene were amplified with PCR and subjected to Sanger sequencing.@*RESULTS@#The clinical manifestation of the patients varied from macrocephaly to severe encephalopathy, with notable phenotypic difference between siblings carrying the same variation. In pedigrees 1 and 2, the probands have carried compound heterozygous variations c.1133C>T(p.Ala378Val) and c.1244-2A>C, which were derived their fathers and mothers, respectively. In pedigree 3, the proband has carried compound heterozygous variation c.339delT (p.Tyr113) and c.406G>T (p.Gly136Cys). Among these, variations c.339delT and c.1133C>T were verified as novel by retrieval of dsSNP, HGMD and 1000 genome database. Bioinformatic analysis suggested that above variations can affect protein function and are probably pathogenic.@*CONCLUSION@#Above discovery has expanded the mutation spectrum of the GCDH gene. No correlation was found between the clinical phenotype and genotype of GA-1 patients.

Encefalopatía hiperamoniémica secundaria a infección urinaria por germen productor de ureasa: Caso clínico pediátrico / Hyperammonemic encephalopathy due to urinary tract infection by urea splitting bacteria: A pediatric case report

El incremento del amonio en sangre, hiperamoniemia, es pasible de provocar compromiso neurológico al atravesar la barrera hematoencefálica. La causa más frecuente y conocida de hiperamoniemia es la alteración en la función hepática. Sin embargo, se deben considerar otras patologías, de menor frecuencia y poco conocidas. La infección del tracto urinario por gérmenes productores de ureasa debe ser contemplada a pesar de ser infrecuente en pediatría. Se reporta el caso de un niño con encefalopatía aguda grave, con niveles elevados de amonio en sangre, en quien, luego de descartar otros diagnósticos diferenciales, se asumió el cuadro como hiperamoniemia secundaria a infección del tracto urinario por Corynebacterium riegelii, un germen productor de ureasa. Se implementaron medidas generales de tratamiento para la encefalopatía hiperamoniémica y tratamiento antibiótico específico, con buena evolución el paciente.

Elevated level of ammonia in the blood, defined as hyperammonemia, is feasible to cause neurological symptoms when crossing the blood-brain barrier. The most frequent and studied cause of hyperammonemia is liver failure. Nevertheless, other less frequent and known etiologies must be considered. Urinary tract infection caused by urea-splitting bacteria, despite being unusual in pediatric patients, must be taken into account. We report a pediatric patient with severe acute encephalopathy and high levels of ammonia in blood. After ruling out other causes of hyperammonemia, it was assumed secondary to urinary tract infection by Corynebacterium riegelii, a ureasplitting bacteria. General treatment for hyperammonemic encephalopathy was established, as well as specific treatment with antibiotics. The patient evolved favorably.

Neurological Complications Resulting from Non-Oral Occupational Methanol Poisoning

Methanol poisoning results in neurological complications including visual disturbances, bilateral putaminal hemorrhagic necrosis, parkinsonism, cerebral edema, coma, or seizures. Almost all reported cases of methanol poisoning are caused by oral ingestion of methanol. However, recently there was an outbreak of methanol poisoning via non-oral exposure that resulted in severe neurological complications to a few workers at industrial sites in Korea. We present 3 patients who had severe neurological complications resulting from non-oral occupational methanol poisoning. Even though initial metabolic acidosis and mental changes were improved with hemodialysis, all of the 3 patients presented optic atrophy and ataxia or parkinsonism as neurological complications resulting from methanol poisoning. In order to manage it adequately, as well as to prevent it, physicians should recognize that methanol poisoning by non-oral exposure can cause neurologic complications.

Effect of glutaryl-CoA dehydrogenase gene silencing and high-concentration lysine on the viability of BRL hepatocytes / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of glutaryl-CoA dehydrogenase (GCDH) gene silencing and accumulation of lysine metabolites on the viability of hepatocytes.</p><p><b>METHODS</b>BRL cells were divided into normal control group, negative control group, and GCDH silencing group. The shRNA lentiviral vector for silencing GCDH gene was constructed, and the BRL hepatocytes in the GCDH silencing group and the negative control group were infected with this lentivirus and negative control virus respectively, and then cultured in a medium containing 5 mmol/L lysine. Immunofluorescence assay was used to measure the infection efficiency of lentivirus. Western blot was used to measure the expression of GCDH protein. MTT assay was used to evaluate cell viability. Hoechest33342 staining was used to measure cell apoptosis. Western blot was used to measure the expression of Caspase-3, an index of cell apoptosis.</p><p><b>RESULTS</b>The lentivirus constructed effectively silenced the GCDH gene in hepatocytes (P<0.01). MTT assay and Hoechest 33342 staining showed no significant differences in cell viability and apoptosis between groups (P>0.05). There was also no significant difference in the expression of Caspase-3 protein between groups (P>0.05).</p><p><b>CONCLUSIONS</b>GCDH gene silencing and accumulation of lysine metabolites may not cause marked hepatocyte injury.</p>

Metronidazole-induced encephalopathy in a patient with Crohn's disease

Metronidazole is a widely used antibiotic for the treatment of anaerobic bacterial infections. Metronidazole-induced encephalopathy (MIEP) is a rare but potentially reversible disease. The mechanism of MIEP remains unclear, and differences in the neurotoxic effects of oral versus intravenous (IV) metronidazole administration have not yet been determined. We report the case of a Crohn's disease (CD) patient who experienced encephalopathy immediately after a single IV dose of metronidazole following long-term exposure to the oral form of the drug. The 64-year-old man with intractable CD experienced a sudden change in mental status, aphasia, and muscle weakness after IV administration of metronidazole. He had previously taken metronidazole orally for 13 years and received intermittent IV metronidazole treatments for CD exacerbation. Brain magnetic resonance imaging (MRI) showed high-intensity signals in the bilateral medial thalamus and the midbrain and pontine tegmentum on fluid-attenuated inversion recovery images. After discontinuation of metronidazole, the high-intensity brain MRI signals resolved and the patient's mental status dramatically improved; however, the patient exhibited mild cognitive dysfunction 2 months after the onset of encephalopathy.

Clinical Characteristics of Transplant-associated Encephalopathy in Children

We aimed to analyze characteristics of encephalopathy after both hematopoietic stem cell and solid organ pediatric transplantation. We retrospectively reviewed medical records of 662 pediatric transplant recipients (201 with liver transplantation [LT], 55 with heart transplantation [HT], and 67 with kidney transplantation [KT], 339 with allogeneic hematopoietic stem cell transplantation [HSCT]) who received their graft organs at Asan Medical Center between January 2000 and July 2014. Of the 662 patients, 50 (7.6%) experienced encephalopathy after transplantation. The incidence of encephalopathy was significantly different according to the type of organ transplant: LT, 16/201 (8.0%), HT, 13/55 (23.6%), KT, 5/67 (7.5%), and HSCT, 16/339 (4.7%) (P < 0.001). Drug-induced encephalopathy (n = 14) was the most common encephalopathy for all transplant types, but particularly after HSCT. Hypertensive encephalopathy was the most common after KT and HT, whereas metabolic encephalopathy was the most common after LT. The median time to encephalopathy onset also differed according to the transplant type: 5 days after KT (range 0–491 days), 10 days after HT (1–296 days), 49.5 days after HSCT (9–1,405 days), and 39 days after LT (1–1,092 days) (P = 0.018). The mortality rate among patients with encephalopathy was 42.0% (n = 21/50). Only 5 patients died of neurologic complications. Transplant-associated encephalopathy presented different characteristics according to the type of transplant. Specialized diagnostic approach for neurologic complications specific to the type of transplant may improve survival and quality of life in children after transplantation.

Limb torsion and developmental regression for one month after hand, foot and mouth disease in an infant / 中国当代儿科杂志

A one-year-old girl visited the hospital due to limb torsion and developmental regression for one month after hand, foot and mouth disease. At the age of 11 months, she visited a local hospital due to fever for 5 days and skin rash with frequent convulsions for 2 days and was diagnosed with severe hand, foot and mouth disease, viral encephalitis, and status epilepticus. Brain MRI revealed symmetric abnormal signals in the bilateral basal ganglia, bilateral thalamus, cerebral peduncle, bilateral cortex, and hippocampus. She was given immunoglobulin, antiviral drugs, and anticonvulsant drugs for 2 weeks, and the effect was poor. Blood and urine screening for inherited metabolic diseases were performed to clarify the etiology. The analysis of urine organic acids showed significant increases in glutaric acid and 3-hydroxyglutaric acid, which suggested glutaric aciduria type 1, but her blood glutarylcarnitine was normal, and free carnitine significantly decreased. After the treatment with low-lysine diets, L-carnitine, and baclofen for 1 month, the patient showed a significant improvement in symptoms. Hand, foot and mouth disease is a common viral infectious disease in children, and children with underlying diseases such as inherited metabolic diseases and immunodeficiency may experience serious complications. For children with hand, foot and mouth disease and unexplained encephalopathy, inherited metabolic diseases should be considered.

Complex heterogeneity phenotypes and genotypes of glutaric aciduria type 1 / 中国当代儿科杂志

Glutaric aciduria type 1 is a rare autosomal recessive disorder. GCDH gene mutations cause glutaryl-CoA dehydrogenase deficiency and accumulation of glutaric acid and 3-hydroxyglutaric acid, resulting in damage of striatum and other brain nucleus and neurodegeneration. Patients with glutaric aciduria type 1 present with complex heterogeneous phenotypes and genotypes. The symptoms are extremely variable. The ages of the clinical onset of the patients range from the fetus period to adulthood. The patients with mild glutaric aciduria type 1 are almost asymptomatic before onset, however, severe glutaric aciduria type 1 may cause death or disability due to acute encephalopathy. Acute metabolic crisis in patients with underlying glutaric aciduria type 1 is often triggered by febrile illnesses, trauma, hunger, high-protein foods and vaccination during a vulnerable period of brain development in infancy or early childhood. The early-onset patients usually have a poor prognosis. Urinary organic acids analysis, blood acylcarnitines analysis and GCDH study are important for the diagnosis of this disorder. Neonatal screening is essential for the early diagnosis and the improvement of prognosis.

Acute hyperammonemic encephalopathy after 5-fluorouracil based chemotherapy

5-Fluorouracil (5-FU) based chemotherapy has been commonly used to treat metastatic or advanced colon cancer as an adjuvant chemotherapy. Although the side effects of 5-FU such as gastrointestinal problems and neutropenia and thrombocytopenia are common, not many cases of 5-FU related encephalopathy are reported. Hyperammonemic encephalopathy is a rare central nervous system toxicity following 5-FU chemotherapy manifesting as altered mental status with elevated ammonia levels with no radiologic abnormality. We report one case of 5-FU induced hyperammonemic encephalopathy occurring after Folfox4 (oxaliplatin, folinic acid and 5-fluorouracil) chemotherapy in a colon cancer patient who presented with confused mental status soon after the chemotherapy and review the 5-FU related encephalopathy.

Perioperative management of a patient with glutaric aciduria: a case report and literature review

Glutaric aciduria type-1 [GA-1] is an autosomal recessive metabolic disorder due to the deficiency of the enzyme glutaryl-CoA dehydrogenase. The enzymatic defect leads to secondary damage to the central nervous system due to the accumulation of glutaric acid. Progressive neurologic effects with spasticity and orthopedic deformities necessitate frequent surgical and anesthetic care. We present a 13-year-old girl with glutaric academia type-1 who required anesthetic care for posterior spinal fusion. Previous reports of anesthetic care for these patients are reviewed, the end-organ involvement discussed, and options for anesthetic care presented

Mutation analysis of GCDH gene in four patients with glutaric academia type I / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To report on clinical features of four patients with glutaric academia type Ⅰ (GA-1) and mutations identified in the glutaryl-CoA dehydrogenase (GCDH) gene.</p><p><b>METHODS</b>All of the patients underwent magnetic resonance imaging (MRI) analysis. Blood acylcarnitine and urine organic acid were analyzed with tandem mass spectrometry and gas chromatographic mass spectrometry. Genomic DNA was extracted from peripheral blood samples. The 11 exons and flanking sequences of the GCDH gene were amplified with PCR and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>Mutations of the GCDH gene were identified in all of the patients. Three had homozygous mutations. A recurrent mutation, IVS10-2A>C, was found in the four unrelated families, while the mutation of c.245G>C (p.Arg82Pro) was novel.</p><p><b>CONCLUSION</b>IVS10-2A>C is likely a founder mutation for Chinese population in Wenzhou.</p>

Clinical and laboratory studies on 28 patients with glutaric aciduria type 1 / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical, biochemical and genetic profiles of 28 Chinese patients with glutaric aciduria type 1.</p><p><b>METHOD</b>Twenty-eight patients with glutaric aciduria type 1 seen in the Department of Pediatrics, Peking University First Hospital from July 2003 to October 2013 were studied. The data of clinical course, laboratory examinations, cranial MRI and GCDH gene mutations of the patients were analyzed.</p><p><b>RESULT</b>(1) Three cases were detected by newborn screening, and the other patients were diagnosed at the age of 2 months to 17 years. (2) 22 patients (79%) were infant onset cases with psychomotor retardation, dystonia, seizures, athetosis, recurrent vomiting, drowsiness or feeding difficulty. Only two of the 22 patients with infant onset got normal intelligence and movement after treatment. Twenty of them were improved slowly with delayed development, dystonia and other neurological problems. Three patients (11%) had late onset. They had motor regression, headache and seizure at the age of 8, 9 and 17 years, respectively. Rapid improvement was observed after treatment. (3) Cranial MRI has been checked in 23 patients; 22 of them showed characteristic widening of the Sylvian fissure, abnormalities of the basal ganglia, leukoencephalopathy and brain atrophy. Thirty-five mutations in GCDH gene of the patients were identified; c.148T>C (p.W50R) was the most common mutation with the frequency of 7.7%; 6 mutations (c.628A>G, c.700C>T, c.731G>T, c.963G>C, c.1031C>T and c.1109T>C) were novel.</p><p><b>CONCLUSION</b>Glutaric aciduria type 1 usually induced neurological deterioration resulting in severe psychomotor retardation and dystonia. Most of our patients were clinically diagnosed. Patients with early onset usually remained having neurological damage. Phenotype and genotype correlation has not been found in the patients. Neonatal screening for organic acidurias should be expanded in China.</p>

Clinical investigation and genetic analysis of a Chinese family with glutaric acidemia type I / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To review the clinical features of a families affected with glutaric acidemia type I (GA-1) and screen potential mutations in glutaryl-CoA dehydrogenase (GCDH) gene.</p><p><b>METHODS</b>Clinical data of the patients and their family members was analyzed. Genomic DNA was extracted from peripheral blood samples. The 11 exons and flanking sequences of the GCDH gene were amplified with PCR and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>Two patients have manifested macrocephaly. Imaging analysis revealed arachnoid cyst and subdural effusion. The elder sister had encephalopathy crisis. The younger sister had significantly raised glutaric acid, whilst the elder sister was normal during the non-acute phase. Genetic analysis has revealed a homozygous c.1244-2A> C mutation of the GCDH gene in both patients.</p><p><b>CONCLUSION</b>The clinical features and mutation of the GCDH gene have been delineated in a Chinese family affected with GA-1. The c.1244-2A> C mutation may be particularly common in the Chinese population.</p>