Organic Acidurias: An Updated Review

Organic acidurias are an important class of inherited metabolic disorders arising due to defect in intermediary metabolic pathways of carbohydrate, amino acids and fatty acid oxidation. This review summarizes the current knowledge about the important organic acidurias in the Indian population. Specifically, diagnosis and principles of treatment of organic acidurias are covered. The salient features of common organic acidurias as well as their prevalence in various parts of the world are reviewed in some detail.     

Urinary Organic Acids Quantitated in a Healthy North Indian Pediatric Population

Human urine gives evidence of the metabolism in the body and contains numerous organic acids and other compounds at a variety of concentration. The concentration of organic acids in urine varies from population to population due to genotype, food habits and other epigenetic and environmental influences. Knowledge of the reference values for urinary organic acids in a healthy pediatric population is very important for critical evaluation. This study was designed to quantify 16 organic acids in a healthy north Indian pediatric population. Early morning urine samples from healthy pediatric subjects of age 1 day to 16 years who did not have symptoms of any disease were analyzed for organic acid content. The children were not on any supplemental vitamins or drugs and were on a free and unrestricted diet. The creatinine concentration of each sample was determined before organic acid analysis. Organic acids were extracted from urine with ethyl acetate, extracted residue was air dried, converted into trimethylsilyl derivatives and analysed by gas chromatography mass spectrometry. Here we reported the age wise mean values and standard deviations for each compound, adjusted for creatinine content (mmol/mol of creatinine). We found the concentration of most of the metabolites are higher in our population in comparison to other populations. Such data may help to provide a basis for diagnosing metabolic abnormalities in patients in a specific ethnicity.     

Maple syrup urine disease: An uncommon cause for neonatal metabolic distress

Maple Syrup Urine Disease is an autosomal recessive disorder caused by a deficiency in the activity of the branched-chain α-ketoacid dehydrogenase complex. This rare disorder represents one of the causes of acute neonatal illness which results in devastating disturbances of neurological development. On investigation of 1750 infants with neurological impairment for inborn errors of amino acid metabolism, 4 neonates with classical maple syrup urine disease were detected. These otherwise normal neonates presented in the first week after birth with seizures, lethargy and refusal of feeds, hypoglycemia and metabolic acidosis. The plasma and urine concentrations of the branched-chain amino acids were increased and there was ketoaciduria. Two of these neonates expired before specific treatment could be instituted. Routine biochemical screening of neonates with acute illness could unearth many cases of this rare inherited metabolic disease.     

Inborn errors of metabolism: Review and data from a tertiary care center

Inherited metabolic disorders are a heterogeneous group of genetic conditions mostly occurring in childhood. They are individually rare but collectively numerous, causing substantial morbidity and mortality. We have retrospectively reviewed a total of eight hundred and sixty nine cases with different age groups that had been referred from several diagnostic centers and hospitals of India to the Department of Metabolism in Narayana Hrudayalaya, as cases suspected with inborn errors of metabolism. Advanced techniques applied were to diagnose the disorders of inborn errors of metabolism. Data analyzed indicates occurrence of several metabolic disorders in our population. The need to screen for an inborn error of metabolism arises out of the fact that most cases take to irreversible effects as time progress. Emphasis has to be laid on early detection and prompt management, which could help in alleviating symptoms and preventing complications and consequent incapacitation.     

低分子量有机酸在火力发电厂热力系统中分布状况的研究

以离子色谱技术为分析手段,对两个不同的火力发电厂和三种不同的热力学参数的热力发电机组水、汽系统中低分子有机酸和相关的无机阴离子作了测定.结果表明,有机污染源对系统中低分子有机酸的含量和分布状况有极大的影响,文中还研究了低分子有机酸在火力发电厂热力系统中的分布特点及机组添加氧化剂(二甲基酮肟)后系统中低分子有机酸含量的变化。     

A case of vitamin B12 deficiency neurological syndrome in a young adult due to late-onset cobalamin C (CblC) deficiency: a diagnostic challenge

Vitamin B12 deficiency can present with neurologic and psychiatric symptoms without macrocytic anaemia. We describe a case of late-onset cobalamin C deficiency which typically presents with normal serum vitamin B12 concentrations, posing an additional diagnostic challenge. A 23-year-old woman with decreased muscle strength and hallucinations was diagnosed with ‘catatonic depression’ and admitted to a residential mental health facility. She was referred to our hospital for further investigation 3 months later. Heteroanamnesis revealed that the symptoms had been evolving progressively over several months. Magnetic resonance imaging (MRI) of the brain showed diffuse symmetrical white matter lesions in both hemispheres. Routine laboratory tests including vitamin B12 and folic acid were normal except for a slight normocytic, normochromic anaemia. Over the next 6 weeks her symptoms deteriorated, and she became unresponsive to stimuli. A new MRI scan showed progression of the white matter lesions. The neurologist requested plasma homocysteine (Hcys) which was more than 8 times the upper limit of normal. Further testing revealed increased methylmalonic acid and the patient was diagnosed with adult-onset cobalamin C deficiency. This case illustrates that Hcys and/or methylmalonic acid should be determined in patients presenting with neuropsychiatric symptoms suggestive of vitamin B12 deficiency with a normal serum vitamin B12 to rule out a late-onset cobalamin C deficiency.     

A Case of Sanfillippo’s Disease Correlating Clinical and Biochemical Findings

The mucopolysaccharidoses (MPSs) are a heterogeneous group of rare inherited disorders caused by deficiency of lysosomal enzyme necessary to break down mucopolysaccharides or glycosaminoglycans (GAGs). We had combined clinical findings and ophthalmological features. Biochemical test for urine glycosaminoglycans was done for confirmation of diagnosis in the patient. The case of Sanfillippo’s disease was characterized by delayed development, hyperactivity with aggressive behaviour. Coarse facial feature, hirsutism and sleep disorder. Urine GAG tests for MPS was positive in the case. Based on clinical findings and biochemical tests for MPS, this case was diagnosed as a type III mucopolysaccharidoses. Urinary GAG’s electrophoresis is an important screening test for MPS suspected cases.     

Acid base status in chronic obstructive pulmonary disease patients

348 patients of chronic obstructive pulmonary diseases (COPD) were studied for their acid base profile using ABL-3 blood gas analyser (Radiometer, copenhagan). 185 patients (53.1%) had simple disorders (respiratory acidosis—53%, respiratory alkalosis—25.4%, metabolic acidosis—11.3%, metabolic alkalosis—10.2%). Mixed disorders were present in 131 patients (34.9%) (respiratory acidosis and metabolic acidosis—75.2%, respiratory acidosis and metabolic acidosis—14%, metabolic acidosis and metabolic alkalosis—5.7%, metabolic alkalosis and respiratory alkalosis—4.9%). Hypoxemia without other acid base abnormalities was observed in early patients of GOPD (42 patients—12%). Chronic respiratory acidosis was the most common finding in advanced cases of COPD (98%). An almost equal number of such patients had a mixed disorder of respiratory acidosis with metabolic alkalosis (91%). Salt restriction, prolonged use of steriods and hypokalemia were often related to metabolic alkalosis in such patients.     

A Rare Case of Mucopolysaccharidosis

Mucopolysaccharidosis are a group of rare metabolic disorders of the lysosomal storage disease family caused by the absence or malfunctioning of lysosomal enzymes responsible for their breakdown. It encompasses disorders in which undegraded or partly degraded glycosaminoglycans accumulate in the lysosomes of many tissues owing to a deficiency of specific lysosomal enzymes. Here we report a case of a 7 years old child displaying the symptoms of Morquio’s disease (Mucopolysaccharidosis type IV). Urine screening tests were performed which gave contrasting results.     

Multiplex PCR for rapid detection of exonal deletions in patients of duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is the most common X-linked disorder in children affecting 1 in 3500 males. Since, as of now, we have no treatment for DMD, carrier detection and prenatal diagnosis is the most important preventive strategy. Multiplex PCR helps in rapid detection of hot spot exonal deletions (positive in 65% of cases) as many exons can be identified in a single run. 10 children with characterstic clinical features of DMD and chorionic villus samples of 10 antenatal patients with positive family history were studied. We identified a deletion mutation in exon 49 of the dystrophin gene in a 4 yr old boy referred with signs and symptoms suggestive of DMD using primers for exons 45, 48, 49, 43, 44, 19, 3, 8, 13 and muscle promoter, subjected to multiplex polymerase chain reaction (PCR) and agarose/Nu-Sieve gel electrophoresis. These genetic methods aid in prenatal diagnosis of DMD as well as confirmation of diagnosis in children with signs and symptoms suggestive of the disease. Work done as WHO fellow in Deptt. of Genetics, All India Institute of Medical Sciences, New Delhi.     

Alkaptonuric ochronosis: Report of a case and brief review

Alkaptonuria, a metabolic disorder characterized by a triad of homogentisic aciduria, arthritis and ochronosis is one of the first conditions in the charter of group of inborn errors of metabolism proposed to have Mendelian recessive inheritance. It is due to the deficiency of the enzyme homogentisic acid oxidase which catalyzes the conversion of homogentisic acid to maleylacetoacetic acid in the catabolism of tyrosine. Homogentisic acid thus accumulates in cells and body fluids and its oxidized polymers bind to collagen, leading to progressive deposition of grey to bluish black pigment resulting in degenerative changes in cartilage, intervertebral disc and other connective tissues, leading to arthritis which is the only disabling effect in an affected older individual. However the diagnosis can be made in neonates when blackish stain is noticed in an unwashed diaper. Alkaptonuria is treated symptomatically, surgical intervention necessitates in advanced stages, treatment with ascorbic acid (Vitamin C) and dietary restrictions of food containing phenylalanine and tyrosine have proved to be successful in alleviating the symptoms.     

A study of prolonged jaundice screen in healthy term babies

Prolonged jaundice in most of the term babies is associated with breast milk but in some cases it can be a marker for a range of hepatobiliary, hematological, metabolic, endocrine, infectious and genetic disorders that are associated with significant mortality and morbidity if not diagnosed in time. A diagnosis of conjugated hyperbilirubinaemia warrants urgent investigation. Protocols for investigating prolonged jaundice screen vary in complexity and the yield from screen has not been assessed. In order to address these issues, we carried out a study on healthy term babies referred to our day unit with prolonged jaundice. Infants were examined by pediatrician and investigations done as per unit protocol. Prolonged jaundice screen was found to be helpful in excluding biliary atresia and to support the diagnosis of breast milk jaundice. Present study concluded that negative prolonged jaundice screen is reassuring in healthy term babies and further investigations are unwarranted unless otherwise specified.     

HPLC method for amino acids profile in biological fluids and inborn metabolic disorders of aminoacidopathies

Quantification of total and individual amino acids in biological fluids such as plasma, urine and cerebrospinal fluid has an important diagnostic implication in laboratory medicine. The present paper describes protocols for the assay of total amino acids by modified method based on dinitrophenyl and HPLC profile involving pre-column derivatization with o-pthalaldehyde (OPA) derivatization, respectively. The method, based on the alkylation of-SH groups prior to OPA derivatization of amino acids followed by reverse phase high performance liquid chromatography, provide a comprehensive profile of more than twenty amino acids (including-SH group containing) in a single run lasting about 45 minutes. The present study, apart from establishing the normal profile of amino acids in plasma of Indian sub population, also presents HPLC profile for some of the rare amino acidopathies.     

关于儿童过敏性紫癜复发的临床影响因素分析

目的：探讨影响儿童过敏性紫癜（Henoch-Schonlein Purpura,HSP）复发的相关因素,以及采取的预防措施。方法：选取2012年01月至2013年12月在某市级儿童医院住院确诊为HSP,初发病例的患儿作为研究对象,进行回顾性分析。共收集364例患儿,其中失访16例,选择符合诊断标准的患儿348例为研究对象。结果：复发组年龄≥7岁构成比、感染发生率、食物过敏发生率、肾脏受累发生率明显高于未复发组,差异显著（P〈0.05）;复发组男女比例为1.77∶1,未复发组男女比例为1.05∶1,两组男女构成比差异具有统计学意义（P〈0.05）;两组在地区（生活农村、城镇）、发病季节、关节症状、消化道症状、皮疹发生率差异无统计学意义（P〉0.05）。结论：对有上述异常指标患儿应加强随访观察,积极寻找、消除诱因,避免疾病复发与恶化。     

Detection of inherited metabolic diseases in children with mental handicap

Mental Retardation is a condition where complex interactions of intrinsic and extrinsic factors hamper mental and sometimes physical growth of the child during developmental period. This study was carried out to detect cause of Mental Retardation in 2000 cases of developmental delay by a multidisciplinary team comprising of a Pediatrician, Cytogeneticist, Biochemist, Psychologist and Speech and Occupational therapists. The causes for developmental delay are broadly divided into Genetic, Environmental and Idiopathic (no specific cause found) factors. The complete diagnosis was possible in 1192(60%) cases. Genetic factors were found in 477(23.8%) cases and environmental factors covered 692(34.6%) cases as a cause of retardation. The most common genetic cause is chromosomal abnormalities which were found in 355 (17.75%) cases. Another major group comprising of 122 (6.1%) cases was that of the disorders which follow Mendelian inheritance. Autosomal recessive conditions, which covers majority of metabolic disorders, are detected in 48(2.4%) cases. During this screening the most common inherited metabolic condition detected is Mucopolysaccharidosis, a Lysosomal Storage Disorder followed by Amino acid abnormalities like Phenylketonuria, Alkaptonuria and Tyrosinuria.     

微生态制剂治疗肝性脑病的研究进展

肝性脑病（hepatic encephalopathy,HE）是由急、慢性肝功能衰竭或各种门-体分流（porto-systemic venous shunting,PSS）引起的以代谢紊乱为基础的、并排除了其它已知脑病的中枢神经系统失调综合征。常以神经精神症状,如性格改变、行为异常、智力减退等为突出表现,发病机制复杂,但经过合理、及时治疗后,该综合征具有潜在的可逆性。如何选择合理有效的药物预防和防止肝性脑病复发,逆转患者的精神神经系统失调已经成为目前研究热点。笔者针对目前微生态制剂药物组成、作用机制、临床疗效及其对治疗肝性脑病的研究进展做一综述。     

有机茄果类蔬菜质量安全标准研究

文章对提高茄果类蔬菜品质的有机生产措施和质量安全指标的设置进行了探讨,包括产地环境、种子、肥料及施肥、植保产品等生产投入品的选择,并在百色田阳进行5亩基地小试,生产的番茄、辣椒品质良好,按GB／T18406．1-2001检测,番茄中百茵清、六六六等29种农残均为未检出（小于检出限）,铬、汞、镉、砷、铅等重金属含量在〈0．001mg／kg至0．056mg／kg之间,氟为0．10mg／kg,亚硝酸盐〈1mg／kg。在此基础上,制定了有机茄果类蔬菜产品广西地方标准。     

A case report of short-chain acyl-CoA dehydrogenase deficiency (SCADD)

Background

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is a rare inherited mitochondrial fatty acid oxidation disorder associated with variations in the ACADS (Acyl-CoA dehydrogenase, C-2 to C-3 short chain) gene. SCADD has highly variable biochemical, genetic and clinical characteristics. Phenotypes vary from fatal metabolic decompensation to asymptomatic individuals.

Subject and methods

A Romani boy presented at 3 days after birth with hypoglycaemia, hypotonia and respiratory pauses with brief generalized seizures. Afterwards the failure to thrive and developmental delay were present. Organic acids analysis with gas chromatography-mass spectrometry (GS/MS) in urine and acylcarnitines analysis with liquid chromatography-tandem mass spectrometry (LC-MS/MS) in dried blood spot were measured. Deoxyribonucleic acid (DNA) was isolated from blood and polymerase chain reactions (PCRs) were performed for all exons. Sequence analysis of all exons and flanking intron sequences of ACADS gene was performed.

Results

Organic acids analysis revealed increased concentration of ethylmalonic acid. Acylcarnitines analysis showed increase of butyrylcarnitine, C4-carnitine. C4-carnitine was 3.5 times above the reference range (<0.68 µmol/L). Confirmation analysis for organic acids and acylcarnitine profile was performed on the second independent sample and showed the same pattern of increased metabolites. Sequence analysis revealed 3-bp deletion at position 310-312 in homozygous state (c.310_312delGAG). Mutation was previously described as pathogenic in heterozygous state, while it is in homozygous state in our patient.

Conclusions

In our case clinical features of a patient, biochemical parameters and genetic data were consistent and showed definitely SCAD deficiency.Key words: SCAD deficiency, short chain acyl-CoA dehydrogenase deficiency, screening, acylcarnitine, polymorphism, genetic     

中医个性化心理护理在肝硬化腹水患者护理中的应用

目的:探讨中医个性化心理护理对肝硬化腹水患者一般症状,临床疗效,以及生活质量的影响。方法:在广西中医药大学第一附属医院肝病科住院病人70例,随机分为中医个性化心理护理组(38例)和普通护理组(32例)。其中中医个性化心理护理组在常规治疗和护理基础上,仅给予中医个性化心理护理;常规护理组仅进行常规的治疗和护理。分析比较两组干预前后的腹围、尿量、疗效,以及生活质量。结果:中医个性化心理护理可有效降低肝硬化腹水病人腹围、尿量,且中医个性化心理护理组的有效率和生活质量均高于普通护理组(均为P0.05)。结论:针对肝硬化腹水患者给予中医个性化心理护理,可有效提高疗效,提高生活质量,具有重要的临床推广价值。     

Quantitation of proteinuria by spot urine sampling

Few studies have shown that calculation of protein/creatinine ratio in a spot urine sample correlates well with the 24-hour urine collection. A study was conducted to compare the accuracy of a spot urinary protein/creatinine ratio (P/C ratio) and urinary dipstick (albustix) with the 24-hour urine protein (24-HUP). Fifty samples from 26 patients were collected. This included a 24-hour urine sample followed by the next voided spot sample. The protein/creatinine ratio was calculated and dipstick (albustix) was performed on the spot sample. This was compared with the 24-hour urine protein excretion. The correlation between the three samples was statistically highly significant (p=<0.001) for all levels of proteinuria. The normal value of protein/creatinine ratio in Indian children was also estimated on 100 normal children attending the OPD and was calculated to be 0.053 (S.E of mean±0.003).