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Methylmalonic acidemia(MMA) is one of the common diseases in hereditary organic acid metabolism disorder. The disorder is mainly treated by using vitamin B12 which comes in various forms.The use of the methylcobalamin and adenosylcobalamin in China cannot meet the needs of children with MMA. Parenteral use of hydroxocobalamin of high concentration has significant advantages in the treatment of MMA. But, the accessibility to hydroxocobalamin is challenging now.Through the supervision and adjustment of hydroxocobalamin, we explored the strategy of using the drugs. Meanwhile, we are considering the oral use of the hydroxocobalamin as supplement to treatment. Solving the challenges of the hydrococobalamin is helpful to meet the treatment of MMA and to provide a new possibility for the use of medication for rare diseases. The improvement in policy and supervision measures will facilitate the development, involvement, and production of hydroxocobalamin, so that the patients will have a good chance of access to the treatment.
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Objective:To observe the clinical features of eyes in children with methylmalonic acidemia (MMA).Methods:A retrospective clinical case study. From June 2019 to June 2022, 13 children with MMA visited on the Department of Ophthalmology of Henan Children's Hospital were included in the study. The anterior segment and fundus were examined under surface or general anesthesia. Best corrected visual acuity (BCVA) and refraction were performed in 9 cases; fluorescein fundus angiography (FFA) was performed in 3 cases; flash electroretinogram (FERG) was performed in 6 cases; flash visual evoked potential (FVEP) was detected in 6 cases; optical coherence tomography (OCT) was performed in 3 cases.Results:Among the 13 pediatric patients with methylmalonic acidemia, 6 cases were male and 7 cases were female. The average age at first visit was 45 months. All cases suffered from hyperhomocysteinemia; 9 cases were with epilepsy; 2 cases were with infantile spasms; 11 cases were with stunting, 13 cases were with repeated pulmonary infection during growth period; 4 cases were with hydrocephalus; 1 cases was with hypertension and renal insufficiency. Genetic dectection results of 8 cases were recorded, MMACHC:c.609G>A:p.W203* mutation site was found in all cases. One case was accompanied by corneal ulcer. There were 10 cases with nystagmus, 4 cases with macular degeneration, 3 cases with hyperopic refractive error and esotropia. Nine cases underwent BCVA examination, BCVA was light perception-0.6. In OCT, 2 cases of 3 cases showed retinal thinning and photoreceptor cell layer atrophy in the macular area. In FFA, 2 cases of 3 cases showed circular transparent fluorescence in the macular area. Five cases of 6 cases who with FVEP had different degrees of P100 peak time delay and decreased amplitude, and 4 cases of 6 cases with FERG had decrease of a and b wave in light and dark adaptation. Conclusions:The clinical phenotypes of eyes in children with MMA are various and the severity was different; most of them are accompanied by nystagmus, and the fundus lesions are common in the characteristic bovine eye like macular region. Those with macular disease have severe visual impairment.
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Objective:To investigate the clinical characteristics and the effectiveness of comprehensive rehabilitation thera-py in patients with late-onset methylmalonic acidemia(MMA). Method:A retrospective analysis was conducted on clinical data of 8 patients with late-onset MMA,including the main symptoms,physical signs,auxiliary examinations,and comprehensive rehabilitation therapy.Compre-hensive rehabilitation therapy consisted of medication and rehabilitation interventions.Medication included,meth-ylcobalamin,betaine,and L-carnitine,while rehabilitation interventions focused on lower limb muscle strength training,balance training,and gait training.Manual muscle testing,Holden walking function classification,and SF-36 quality of life scores were collected from 6 patients before and after comprehensive rehabilitation therapy,and the Wilcoxon signed-rank test was used for pre-and post-treatment analysis. Result:Among the 8 patients,1 was asymptomatic,while the remaining 7 exhibited initial symptoms such as neuropsychiatric abnormality including dull reaction,memory loss,and mental apathy,as well as motor impair-ments including unstable gait.Multiple systemic impairments such as joint pain,anemia,and thrombosis were also observed.The most prominent finding on cranial MRI in 6 patients was cerebral atrophy,while l patient showed abnormal signal in the cerebellum on cranial MRI.The two most common mutations in the MMACHC gene were c.482G＞A and c.394C＞T.After 12 weeks of treatment,the patients exhibited disappear-ance of psychiatric symptoms,improvement in lower limb muscle strength,Holden walking function classifica-tion,and SF-36 scores,with statistically significant differences(P＜0.05). Conclusion:Late-onset MMA demonstrates high clinical heterogeneity.For patients presenting with motor im-pairments and psychiatric abnormalities,the possibility of this metabolic disorder should be considered.Compre-hensive rehabilitation therapy can significantly ameliorate psychiatric and behavior symptoms,muscle strength,walking function,and health-related quality of life in late-onset MMA patients.
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Objective:To investigate the incidence rate and gene variation of methylmalonic academia (MMA) in Ji′nan city by analyzing biochemical and genetic screening results, and to explore the carrier frequency of MMA-related pathogenic genes in the population in Ji′nan.Methods:The children diagnosed with MMA by tandem mass spectrometry screening in Ji′nan Neonatal Disease Screening Centre from May 2011 to May 2022 were enrolled in this study.Their genetic test results were retrospectively analyzed and summarized.The dried heel blood tablets collected from 6 800 newborns were tested for neonatal gene screening. MMAA, MMAB, MMACHC and MMUT genes in 4 800 cases were detected by high-throughput sequencing+ target area capture technology.Ultra-multiplex polymerase chain reaction+ target gene locus capture technology was used to detect 174 target loci of 8 genes related to MMA in 2 000 cases.The hotspot mutation and related gene carrier rate of MMA were analyzed. Results:A total of 367 452 newborns were screened by tandem mass spectrometry, and 103 cases (56 males and 47 females) were diagnosed with MMA by screening.The estimated incidence of MMA was 1∶3 567.Among the 103 MMA cases, 76 were genetically diagnosed, and 4 gene variants of MMA ( MMAHC, MMUT, MMAA, MMADHC) were identified.A total of 6 800 neonates underwent neonatal genetic screening.Three of them were diagnosed with MMA.About 318 infants carried pathogenic variants of MMA, with a total carrier rate of 4.68%.Specifically, the carrier rates of MMACHC and MMUT gene variants were 3.09%(210/6 800) and 1.43% (97/6 800), respectively. Conclusions:MMA is the most common organic acid metabolism disorder in our country.The incidence and carrier rate of this disease are high in Jinan city.Neonatal genetic screening is an important supplement to neonatal biochemical screening.Carrier screening for MMA-related pathogenic genes is recommended for couples of childbearing age in Jinan.
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Resumen Los errores innatos del metabolismo intermediario (EIMi) son un grupo de enfermedades monogénicas que afectan alguna vía del metabolismo de las proteínas, los hidratos de carbono o los lípidos; cuando no son tratados a tiempo, se asocian con una elevada morbimortalidad. A la fecha, la piedra angular del tratamiento de los EIMi ha sido la terapia nutricional, cuyo propósito es evitar la acumulación de metabolitos tóxicos al restringir los sustratos que están involucrados en la vía afectada. El manejo nutricional en lactantes incluye una fórmula metabólica sin los nutrimentos involucrados en el EIMi más el aporte de alimentación al seno materno o fórmula infantil. Por el perfil de aminoácidos, la proporción de ácidos grasos esenciales y la protección contra enfermedades, la leche materna resulta un alimento ideal para los pacientes con EIMi. El objetivo de esta revisión de la literatura sobre la lactancia materna en algunos EIMi es servir de guía para el personal de salud involucrado en la atención médica de estos pacientes. La lactancia materna puede ser llevada a cabo de forma exitosa en pacientes con EIMi siempre que exista un seguimiento estrecho y continuo, de preferencia en centros especializados. El profesional de la nutrición y el pediatra deben individualizar las recomendaciones para proporcionar una lactancia a libre demanda en conjunto con una fórmula metabólica o una lactancia materna cuantificada, y con ello lograr una adecuada evolución en estos pacientes.
Abstract Inborn errors of intermediary metabolism (IEiM) are a group of monogenic disorders that affect a metabolic pathway of proteins, carbohidrates, or lipids; when not treated timely, IEiM are associated with high morbidity and mortality. To date, nutritional therapy is the cornerstone of treatment for patients with IEiM, which aims to prevent the accumulation of toxic metabolites by restricting the substrates involved in the affected pathway. Nutritional management in infants includes a metabolic formula free of the nutrients involved in IEiM and breastmilk or infant formula. Because of its amino acid profile, the content of essential fatty acids, and protection against disease, breast milk is an excellent food for patients with IEiM. This literature review on breastfeeding in some IEiM aims to serve as a guide for health care personnel involved in the medical care of these patients. Breastfeeding can be successfully carried out in patients with IEiM as long as there is a close and continuous follow-up, preferably in specialized centers. The nutrition professional and the pediatrician should individualize the recommendations to provide on-demand breastfeeding in conjunction with metabolic formula or quantified breastfeeding to achieve a good clinical evolution in this group of patients.
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To analyzed a case of pediatric patient with propionic acidemia combined with dilated cardiomyopathy retrospectively, who underwent living donor liver transplantation at the Liver Transplantation Center, Beijing Friendship Hospital, Capital Medical University in March 2019.A 2 years and 6 months female child was admitted to hospital for propionic acidemia.The pretransplant echocardiogram showed left ventricular dilatation and systolic dysfunction, and thus dilated cardiomyopathy was considered.A living donor liver transplant was performed using her mother′s left latera-llobe.On the 14 months postoperatively, the child was on a liberated protein diet, but still required levocarnitine supplementation.Her hepatic and cardiac function returned normal, but growth retardation was still present.During the follow-up period, further propionic acidemia-related complications like metabolic decompensation, or any transplant-related complications were not reported.This case report suggested that liver transplantation is effective on pediatric propionic acidemia combined with cardiomyopathy, which reverses cardiomyopathy, improves cardiac function, relieves strict protein restriction, reduces the risk of metabolic decompensation, and significantly improves quality of life.
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Late onset methylmalonic acidemia (MMA) is a rare genetic metabolic disease.This case is a 46 year old adult patient with MMA complicated with hyperhomocysteinemia.It starts with progressive limb weakness and mental abnormality, and has dysuria and respiratory failure.Neurological examination showed decreased muscle strength of limbs and pyramidal tract sign.The levels of blood homocysteine and urinary methylmalonic acid increased significantly.Head, neck, thoracolumbar magnetic resonance imaging showed abnormal signals in the spinal cord from the level of foramen magnum to the level of lumbar 1 vertebral body.Two heterozygous variants of mmachc were found by gene detection: c: 609G>A, c: 349G>A, consistent with cobalamin C deficiency.Treat with L-carnitine, vitamin B12 and betaine.The patients′ mental symptoms, limb muscle strength and respiratory failure were improved, and the level of blood homocysteine also decreased significantly.
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Abstract Glycogen storage disease type I is an autosomal recessive disorder of carbohydrate metabolism that manifests mainly by hepatomegaly and hypoglycemia with short fasts. Despite strict therapy, patients present long-term renal and liver complications. Data of 36 patients,29 GSD Ia and 7 Ib from a high complexity Hospital in Argentina was collected retrospectively. Collected data included diagnosis, anthropometric, biochemical parameters, therapy and follow-up. Treatment increased Height SDS (p=0.012). Patients with good adherence to therapy presented better growth parameters (p=0.049). Instead, admissions were detrimental (p =0.031) and were more common in Ib patients (p=0.002). The early appearance of complications (liver adenomas and nephropathy) was related to sustained triglyceride values > 500mg / dl (p=0.009 and 0.046 respectively). With intensive dietary treatment, clinical and biochemical status improves but cannot be completely corrected in most patients. Growth improves with treatment and this is optimized with adequate adherence. We must take into account that with ageing, more complications will develop.
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La linfohistiocitosis hemofagocítica (LHH) puede ser primaria (hereditaria) o secundaria a infecciones, tumores malignos, trastornos reumatológicos, síndromes de inmunodeficiencia y metabolopatías. Se informaron casos de intolerancia a la proteína lisinúrica, deficiencia de múltiples sulfatasas, galactosemia, enfermedad de Gaucher, síndrome de Pearson y galactosialidosis. No se sabe cómo se desencadena la LHH en las metabolopatías. Se diagnosticó LHH en un lactante de 2 meses con letargo, palidez, alimentación deficiente, hepatoesplenomegalia, fiebre y pancitopenia, y se instauró el protocolo HLH-2004. Se realizaron, en conjunto, análisis para detectar mutaciones genéticas y pruebas metabólicas; los resultados fueron negativos para las mutaciones genéticas de LHH primaria, pero se detectaron hiperamoniemia y concentración elevada de metilcitrato. Se diagnosticó acidemia propiónica. Aquí informamos sobre un caso de LHH secundaria a acidemia propiónica. Es posible la realización simultánea de pruebas de detección de trastornos metabólicos y de mutaciones genéticas para el diagnóstico temprano en los lactantes con LHH
Hemophagocytic lymphohystiocytosis (HLH) may be primary (inherited/familial) or secondary to infections, malignancies, rheumatologic disorders, immune deficiency syndromes and metabolic diseases. Cases including lysinuric protein intolerance, multiple sulfatase deficiency, galactosemia, Gaucher disease, Pearson syndrome, and galactosialidosis have previously been reported. It is unclear how the metabolites trigger HLH in metabolic diseases. A 2-month-old infant with lethargy, pallor, poor feeding, hepatosplenomegaly, fever and pancytopenia, was diagnosed with HLH and the HLH-2004 treatment protocol was initiated. Analysis for primary HLH gene mutations and metabolic screening tests were performed together; primary HLH gene mutations were negative, but hyperammonemia and elevated methyl citrate were detected. Propionic acidemia was diagnosed with tandem mass spectrometry in neonatal dried blood spot. We report this case of HLH secondary to propionic acidemia. Both metabolic disorder screening tests and gene mutation analysis may be performed simultaneously especially for early diagnosis in infants presenting with HLH.
Subject(s)
Humans , Male , Infant , Lymphohistiocytosis, Hemophagocytic/diagnosis , Propionic Acidemia/diagnosis , Pancytopenia , Splenomegaly , Lymphohistiocytosis, Hemophagocytic/drug therapy , Propionic Acidemia/drug therapy , Torpor , Continuous Renal Replacement Therapy , HepatomegalyABSTRACT
La acidemia propiónica es una rara enfermedad metabólica (prevalencia: 1/100 000), cuya detección puede hacerse de forma precoz mediante el cribado neonatal en las primeras 72 horas de vida. Puede tener una presentación neonatal grave, tardía intermitente o crónica progresiva. El tratamiento de las crisis consiste en la inversión del catabolismo que detiene la ingesta proteica con aporte intravenoso de calorías no proteicas. La mortalidad depende, fundamentalmente, de los episodios de descompensación aguda, mientras que la evolución asocia una alta tasa de secuelas neurológicas y déficits cognitivos.Se presenta el caso de una recién nacida de 11 días de vida con clínica de estancamiento ponderal, letargia, acidosis metabólica e hiperamonemia, que, debido a una falla en el proceso de cribado, no se benefició del diagnóstico precoz.A pesar de la ya existente detección por cribado, es vital mantener un alto índice de sospecha en casos sugestivos de metabolopatías.
Propionic acidemia is a rare metabolic disease (prevalence 1/100,000) that can be early detected with the newborn metabolic screening within the first 72 hours of life. It can have a severe neonatal presentation, a late intermittent onset or a chronic and progressive course. The treatment in the crisis consists in inverting the catabolism by pausing the protein intake and giving intravenous non-protein calories. Mortality depends mainly on acute episodes of decompensation, while evolution and prognosis associate a high rate of neurological sequelae and cognitive deficiencies.We present the case of an 11-day-old female newborn with failure to thrive, lethargy, metabolic acidosis and hyperammonemia that, because of a failed newborn screening process, could not be early diagnosed.In spite of the existence of early detection with the newborn metabolic screening, it is very important to keep a high suspicion in cases that suggest metabolic disorders.
Subject(s)
Humans , Female , Infant, Newborn , Neonatal Screening , Propionic Acidemia/diagnosis , Propionic Acidemia/drug therapy , Sepsis , HyperammonemiaABSTRACT
OBJECTIVE@#To investigate the incidence,clinical,biochemical and genetic characteristics of isovaleric acidemia (IVA) in Zhejiang province.@*METHODS@#Between January 2009 and December 2019, a total of 3 510 004 newborns were screened for IVA using tandem mass spectrometry. Patients of IVA were confirmed by urine organic acid and @*RESULTS@#A total of 15 patients with IVA were diagnosed, with an incidence of 1/234 000. Three patients had acute neonatal IVA, and the rest were asymptomatic. The isovalerylcarnitine (C5) levels were increased in all patients. Twelve children underwent urinary organic acid analysis, of which 11 cases had elevated isovalerylglycine levels, 4 cases with 3-hydroxyisovalerate increased simultaneously. Eleven IVA patients underwent genetic testing, 9 patients were compound heterozygous variants in @*CONCLUSIONS@#The clinical manifestations of IVA are non-specific, and the gene spectrum is scattered. Newborn patients screened by tandem mass spectrometry can receive early diagnosis and treatment, so as to correct metabolic defects and pathophysiological changes.
Subject(s)
Child , Humans , Infant, Newborn , Amino Acid Metabolism, Inborn Errors/epidemiology , China/epidemiology , Isovaleryl-CoA Dehydrogenase/genetics , Mutation , Neonatal Screening , Tandem Mass SpectrometryABSTRACT
Abstract Methylmalonic acidemia (MMA) should be diagnosed in early infancy and receive appropriate management promptly after the diagnosis to prevent severe complications leading to death. At present, a newborn screening (NBS) method using tandem mass spectrometry (MS/MS) identifies suspected patients with MMA by elevated propionylcarnitine. In addition, a liquid chromatography tandem mass spectrometry (LC/MS/MS) method using dried blood spot is effective to detect some metabolites as a second-tier test, and reduces the false-positive rate in NBS. However, these tests were only used in screening, and not applied as an examination for evaluating treatment. Herein, we describe a 57-day-old girl with MMA under treatment with cobalamin who had elevated urinary methylmalonic acid levels. We applied the LC/MS/MS method with a separation column to evaluate her cobalamin responsiveness, and discovered an insufficient cobalamin dose earlier than would have been possible using other methods. Based on the current data, this method seems to be applicable for the follow-up of the treatment of MMA patients. However, this should be confirmed with more experience with a larger number of cases and a wider spectrum of disorders.
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Cobalamin C (CblC) deficiency is an autosomal recessive disorder caused by mutations of the MMACHC gene that results in impaired synthesis of the methylcobalamin and adenosylcobalamin co-factors. This brings an impaired conversion of dietary cobalamin and therefore dysfunction of two key enzymes generating hyperhomocysteinemia, hypometionimemia and methylmalonic aciduria. It is the most common intracellular metabolism disorder of cobalamin. The early clinical form is the most frequent disorder and appears as a multisystemic disease with developmental delay, failure to thrive, and ocular, renal and hematological involvement during the first year of life. The thromboembolic events are associated with small vessel involvement, generating thrombotic microangiopathy responsible for renal involvement and pulmonary thromboembolism. The late-onset form is characterized by leukoencephalopathy, psychiatric disorders, subacute degeneration of the spinal cord, and thromboembolic events of medium to large vessels. The treatment currently available increases the survival of the patient and improves growth, neurological manifestations, biochemical, hematological profile and hydrocephalus. We present the neonatal debut of a case of CblC deficiency that appeared as a multisystem disease with initial neurological, ocular and hematological manifestations. The onset of symptoms was acute, a characteristic that is not frequent in CblC. The patient started treatment early, but in an unsatisfactory fashion, which led to increased neurological deterioration. Due to MRI images performed during the evolution of his condition, a superior and transverse sagittal sinus thrombosis, a rare manifestation of the disease, was observed.
La deficiencia de cobalamina C (CblC) es un defecto autosómico recesivo causado por la mutación del gen MMACHC, que resulta en la síntesis alterada de los cofactores metilcobalamina y adenosilcobalamina. Esto trae aparejado una disfunción de dos enzimas claves, lo cual genera hiperhomocisteinemia, hipometionimemia y aciduria metilmalónica. La presentación clínica de la deficiencia de CblC es heterogénea, y varía desde las formas de inicio temprano graves y potencialmente mortales, hasta los fenotipos más leves de inicio tardío. La forma clínica temprana es la más frecuente y se manifiesta como una enfermedad multisistémica, con restricción del desarrollo, restricción del crecimiento y alteraciones oculares, renales y hematológicas durante el primer año de vida. Las manifestaciones tromboembólicas están asociadas con el compromiso de pequeños vasos, lo que causa microangiopatía trombótica, responsable de compromiso renal y de tromboembolismo pulmonar. La forma tardía se caracteriza por leucoencefalopatía, trastornos psiquiátricos, degeneración subaguda de la médula espinal y eventos tromboembólicos de medianos o grandes vasos. El tratamiento disponible actualmente aumenta la supervivencia de la enfermedad y mejora el crecimiento, las manifestaciones neurológicas, el perfil bioquímico y hematológico y la hidrocefalia. Presentamos el debut neonatal de un caso de deficiencia de CblC que se manifestó con compromiso inicial neurológico, ocular y hematológico. El comienzo de los síntomas fue agudo, característica que no es frecuente en la deficiencia de CblC. El tratamiento se inició tempranamente, pero en forma insatisfactoria, con evolución de deterioro neurológico. En la evolución de su enfermedad en las imágenes de resonancia magnética, se puso de manifiesto trombosis de los senos sagital superior y transversos, una rara manifestación de la deficiencia de CblC.
Subject(s)
Humans , Infant, Newborn , Infant , Sinus Thrombosis, Intracranial , Vitamin B 12 , Vitamin B 12 Deficiency , Venous Thrombosis , Hyperhomocysteinemia , PediatricsABSTRACT
Isovaleric Acidemia (IVA) is inherited as an autosomal recessive trait, caused by the deficiency of the enzyme isovaleryl CoA dehydrogenase. It has the prevalence of 1 in 62,500 (in parts of Germany) to 1 in 250,000 live births (in the United States). Acute episodes of metabolic decompensations may occur, which may mimic sepsis, ketosis or shock. Early diagnosis & early initiation of treatment has been reported to correlate with a good neurocognitive outcome. This is case of child presenting in Paediatric emergency department with fever, vomiting, increased respiratory activity and lethargy. Child had GCS score of 8/15, acidotic breathing, hypotonia with hyporeflexia. Sepsis screen, metabolic work up and neuroimaging were all normal except for high anion Gap acidosis with ketosis. So further neurometabolic screening work up was done in view of persistent metabolic acidosis, developmental delay, and bad obstetric history in mother. It revealed increased excretion of isovalerylglycine 1(IVG 1), Isovalerylglycine 2 (IVG2) Lactate, 3-Hydroxypropionate (3HP) and 3-Hydroxybutyrate (3 HB).Serum lactate 358.54 (control 1.1-208.1) confirming the diagnosis of Isovaleric Acidemia. After recovery from the acute attack, the patient was advised low-protein diet (1.0-1.5 g/kg/24 hrs.) and carnitine (100 mg/kg/24 hrs. orally) supplements. On follow up child is asymptomatic & showing neurological improvement as he started achieving further developmental milestones during 6 months follow up.Early diagnosis and early treatment of IVA cases definitely results in favorable outcome and better prognosis. But chronic intermittent cases presenting late should not be neglected, proper medical management can reverse neuromotor consequences in them also.
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La acidemia propiónica es un trastorno infrecuente con patrón de herencia autosómico recesivo causado por la deficiencia de la enzima mitocondrial propionil-CoA carboxilasa, que convierte el propionil-CoA a D-metilmalonil-CoA. Se expone el caso de un recién nacido masculino con signos de dificultad respiratoria, vómitos y cansancio durante la alimentación. Presentó acidosis metabólica, cuerpos cetónicos en el suero y la orina positivos, hiperamonemia, anemia, trombocitopenia e hipoproteinemia. El estudio bioquímico por cromatografía de gases acoplada a espectrometría de masas en la muestra de orina fue sugestivo de acidemia propiónica. El estudio molecular en el gen PCCA encontró las mutaciones c.893A>G (p.K298R) en el padre y c.937C>T (p.R313X) en la madre. Existe la necesidad de establecer el diagnóstico de esta entidad infrecuente para implementar las medidas terapéuticas disponibles y aportar el oportuno asesoramiento genético.
Propionic acidemia is an infrequent disorder with an autosomal recessive inheritance pattern caused by the deficiency of the mitochondrial enzyme propionyl-CoA carboxylase that converts propionyl-CoA to D-methylmalonyl-CoA. We present the case of a male newborn who showed signs of respiratory distress, vomiting and tiredness during feeding. He presented metabolic acidosis, positive serum and urine ketone bodies, hyperammonemia, anemia, thrombocytopenia and hypoproteinemia. The biochemical study by gas chromatography coupled to mass spectrometry in a urine sample was suggestive of propionic acidemia. The molecular study in the PCCA gene found the mutations c.893A>G (p.K298R) in the father and c.937C> T (p.R313X) in the mother. There is a need to establish the diagnosis of this infrequent entity to implement the therapeutic measures available and provide the appropriate genetic counseling.
Subject(s)
Humans , Male , Infant, Newborn , Inheritance Patterns , Methylmalonyl-CoA Decarboxylase , Propionic Acidemia , Genetic CounselingABSTRACT
RESUMEN Introducción: La acidemia propiónica (AP) es una acidemia orgánica (AO) con presentación clínica de inicio neonatal o de forma tardía. Causada por deficiencia de la enzima propionil-CoA carboxilasa que ocasiona acumulación de ácido propiónico y metabolitos relacionados con propionil-CoA en los tejidos. Es característica la hiperglicinemia, pero puede presentarse hiperlisinemia. Este trabajo describe un caso clínico de AP de inicio neonatal con desenlace fatal y alteración llamativa de los aminoácidos. Caso clínico: Recién nacido (RN) femenina ingresa a unidad neonatal al tercer día de vida por hipoactividad, vómito y letargia. Posterior dificultad respiratoria y realiza paros cardiacos, falleciendo antes de establecer un diagnóstico bioquímico. Paraclínicos iniciales evidenciaron acidosis metabólica, leucopenia, hipoglicemia, posteriormente se documenta hiperglicininemia, hipercistinemia y severa hiperlisininemia. La cromatografía de ácidos orgánicos en orina identificó ácido 3-hidroxi-propionico, metilcitrato y propionilglicina entre otros metabolitos tóxicos, confirmando el diagnóstico. Conclusiones: La AP es un error innato del metabolismo autosómico recesivo de baja incidencia. La presencia de acidosis metabólica severa, pancitopenia, hipoglicemia y antecedentes familiares deben alertar sobre este diagnóstico. Adicionalmente, aunque el diagnóstico bioquímico definitivo son los ácidos orgánicos en orina, la presencia de hiperamonemia, hiperglicinemia e hiperlisinemia pueden ser altamente sugestivas de este trastorno.
ABSTRACT Introduction: Propionic acidemia (AP) is an organic acidemia (AO) with clinical presentation of neonatal onset or late. Caused by deficiency of the enzyme propionil-CoA carboxilasa that causes accumulation of propionic acid and metabolites related to propionyl-CoA in tissues. Hyperglycinemia is characteristic, but hyperlysinemia may occur. This work describes a clinical case of AP of neonatal onset with fatal outcome and striking alteration of amino acids. Clinical case: Female newborn (RN) admitted in the neonatal unit on the third day of life due to hypoactivity, vomiting and lethargy. Subsequent respiratory distress and cardiac arrest occurred, dying before a biochemical diagnosis was established. Initial paraclinics evidenced metabolic acidosis, leukopenia, hypoglycemia, later documented hyperglycinemia, hypercystinemia and severe hyperlysinemia. The organic acid chromatography in urine identified 3-hydroxy-propionic acid, methyl citrate and propionylglycine among other toxic metabolites, confirming the diagnosis. Conclusions: AP is an inborn error of autosomal recessive metabolism of low incidence. The presence of severe metabolic acidosis, pancytopenia, hypoglycemia and family history should alert about this diagnosis. Additionally, although the definitive biochemical diagnosis is organic acids in urine, the presence of hyperammonemia, hyperglycinemia and hyperlysinemia can be highly suggestive of this disorder.
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Methylmalonic acidemia is the most common disease of congenital organic acid metabolic disorders,and it is an autosomal recessive disease.The clinical manifestations of methylmalonic acidemia are non-specific.It is characterized by the neurological symptoms.Cardiovascular diseases have little been associated with methylmalonic acidemia.But,cardiovascular diseases including structural heart disease,pulmonary hypertension,cardiomyopathy,hypertension,arrhythmias,may cause rapid deterioration,or even sudden death.This paper is a review of cardiovascular diseases of methylmalonic acidemia.
ABSTRACT
Objective@#To report on clinical characteristics and genetic findings in 15 Chinese patients with methylmalonic acidemia (MMA).@*Methods@#For the 15 MMA patients detected by tandem mass spectrometry, genetic analysis was carried out in twelve pedigrees. Clinical characteristics, genetic finding, treatment and outcomes were retrospectively analyzed.@*Results@#The main features of the patients included poor feeding, recurrent vomiting, lethargy, seizure and development retardation. Blood propionylcarnitine (except for 3 patients), its ratio with acetylcarnitine, and urine methylmalonic acid were increased in all patients. Twelve patients were diagnosed genetically, which included 7 with MUT variants, 4 with MMACHC variants, and 1 with MMAB variant. Nine MUT variants were detected, among which c. 1159A>C, 753+ 1delGinsTGGTTATTA and c. 504del were novel. Six known pathogenic MMACHC variants and two novel MMAB variants (c.289_290delGG, c. 566G>A) were also detected. Seven patients died of metabolic crises within a year, others had improved effectively following the treatment, but had mild to severe growth delay and/or developmental retardation.@*Conclusion@#The clinical manifestation of MMA are complex. Most patients have variants of the MUT and MMACHC genes. High mortality may occur before one year of age.
ABSTRACT
Propionic acidemia or propionic aciduria,is a rare autosomal recessive inherited metabolic disease.It is a metabolic disorder of branched amino acids and odd-chain fatty acids caused by propionyl-CoA carboxylase deficiency,resulting in brain,heart,liver,bone marrow or multi-organ damages leading to disabilities even death.Patients with propionic acidemia have various clinical manifestations.Most patients presented in the neonatal period or early infancy.Nonspecific clinical presentations of the patients make the clinical diagnosis difficult,a definite diagnosis relies on the blood amino acids and acylcarnitines determination,urine organic acids analysis,and gene testing.The treatment for the patients in acute and stable phase should be individualized,including L-carnitine,dietary management,symptomatic intervention and liver transplantation.If not treated timely,patients have a high risk of death and disability.Early screening,diagnosis and treatment can greatly improve the patients' clinical outcomes.
ABSTRACT
Methylmalonic acidemia (MMA) is a rare autosomal recessive disorder, with the manifestation of recurrent and severe episodes of acute metabolic decompensation or a variety of long-term complications that require timely treatment.As liver transplantation (LT) developing widely, it has become an effective treatment for patients with severe MCM deficiency.Although LT does not solve the fundamental problem of gene defect, it can prolong survival, improve the quality of life of patients and reduce recurrent hospitalization rate, as well as lower urine, plasma MMA and propionyl carnitine levels and prevent metabolic stroke.After LT, the metabolism-correcting medications are still partially needed.Neurological symptoms of some patients can be alleviated but renal damage may remain irreversible.The domestic liver transplantation in the treatment of methylmalonic acidemia is being carried out, but there is still a lack of research on the effect of LT on MMA.The paper is to make a review of the clinical value of liver transplantation in the treatment of methylmalonic acidemia in recent years in hope of sharing the information on this issue with more people.