Maple syrup urine disorder

BACKGROUND: Episodic ataxia (EA), characterized by recurrent attacks of cerebellar dysfunction, is the manifestation of a group of rare autosomal dominant inherited disorders. EA1 and EA2 are most frequently encountered, caused by mutations in KCNA1 and CACNA1A . EA3-8 are reported in rare families. Advances in genetic testing have broadened the KCNA1 and CACNA1A phenotypes, and detected EA as an unusual presentation of several other genetic disorders. Additionally, there are various secondary causes of EA and mimicking disorders...

Background: Maple syrup urine disease (MSUD) is a rare autosomal recessive amino acid metabolic disease. This study is to identify the pathogenic genetic factors of six cases of MUSD and evaluates the application value of high-throughput sequencing technology in the early diagnosis of MUSD. Methods: Clinical examination was carried out for patients and used blood tandem mass spectrometry (MS/MS), urine gas chromatography-mass spectrometry (GC/MS), and the application of high-throughput sequencing technology for detection...

BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive genetic disorder caused by defects in the catabolism of the branched-chain amino acids (BCAAs). However, the clinical and metabolic screening is limited in identifying all MSUD patients, especially those patients with mild phenotypes or are asymptomatic. This study aims to share the diagnostic experience of an intermediate MSUD case who was missed by metabolic profiling but identified by genetic analysis. CASE SUMMARY: This study reports the diagnostic process of a boy with intermediate MSUD...

Maple syrup urine disease (MSUD) is a metabolic disorder characterized by a difficulty to digest and process proteins necessary for growth. To monitor and maintain the ideal growth of children with MSUD, caregivers need to carefully control the consumption of harmful branched-chain amino acids (BCAAs). The dietary limits of amino acids for MSUD patients are recommended and controlled by pediatricians and metabolic dietitians according to age, height, weight, and the prevailing percentage of amino acids in the body...

First-tier MS-based newborn screening by flow injection analysis can have high presumptive positive rates, often due to isomeric/isobaric compounds or poor biomarker specificity. These presumptive positive samples can be analyzed by second-tier screening assays employing separations such as liquid chromatography-mass spectrometry (LC-MS/MS), which increases test specificity and drastically reduces false positive referrals. The ability to screen for multiple disorders in a single multiplexed test simplifies workflows and maximizes public health laboratories' resources...

A metabolic disorder is due to a gene mutation that causes an enzyme deficiency which leads to metabolism problems. Maple Syrup Urine Disease (MSUD) is one of the most common and severe hereditary metabolic disorders in Saudi Arabia. Patients and families were burdened by complex and regular dietary therapy menus because of the lack of information on food labels, it was also difficult to keep track of MSUD's typical diet. The prototype smart plate system proposed in this work may help patients with MSUD and their caregivers better manage the patients' MSUD diet...

BACKGROUND: Organic acidurias are a group of inborn errors of metabolism with a significant diagnostic challenge and serious morbidities and mortalities. They are considered the most frequent inborn errors of metabolism among high-risk children. Gas chromatography-Mass spectrometry is a reliable diagnostic technique for organic acidurias. This hospital-based study aimed to quantify the frequency of organic acidurias among a group of high-risk Egyptian pediatric patients, and to highlight the importance of the high-risk screening for such disorders...

OBJECTIVES: Maple syrup urine disease (MSUD) is an autosomal recessive inherited disorder. Despite the advances in medical nutrition therapies, classical phenotype causes severe neurological disorders and sudden death. It is known that MSUD patients do not experience metabolic attacks despite their free diet after liver transplantation (LT). This study aims to reveal the long-term results, development, mental, motor, intellectual and nutritional status of MSUD patients who underwent LT...

RATIONALE: The main clinical symptoms of maple syrup urine disease (MSUD) are dehydration, acidosis, nervous system symptoms and intellectual disability. The brain imaging findings were mainly caused by cytotoxic edema. The lesions usually occur at the site consistent with the myelination process of normal neonates. The distribution is mostly symmetric, and the diffusion is obviously limited. PATIENT CONCERNS: Herein, we report a rare case of an 8-day-old female patient who presented with abnormal symptoms, such as difficulty eating, convulsions, slow reaction, difficulty in correcting hypoglycemia and severe metabolic disorders...

Inborn errors of metabolism (IEM) constitute a huge group of rare diseases affecting 1 in every 1000 newborns. Next-generation sequencing has transformed the diagnosis of IEM, leading to its proposed use as a second-tier technology for confirming cases detected by clinical/biochemical studies or newborn screening. The diagnosis rate is, however, still not 100%. This paper reports the use of a personalized multi-omics (metabolomic, genomic and transcriptomic) pipeline plus functional genomics to aid in the genetic diagnosis of six unsolved cases, with a clinical and/or biochemical diagnosis of galactosemia, mucopolysaccharidosis type I (MPS I), maple syrup urine disease (MSUD), hyperphenylalaninemia (HPA), citrullinemia, or urea cycle deficiency...

Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder of branched-chain amino acid metabolism caused by mutations in BCKDHA , BCKDHB , and DBT that encode the E1α, E1β, and E2 subunits of the branched-chain α-ketoacid dehydrogenase (BCKD) complex. Various MSUD-causing variants have been described; however, no structural rearrangements in BCKDHA have been reported to cause the classic MSUD phenotype. Here, we describe the classic patient with MSUD with compound heterozygous pathogenic variants in BCKDHA : a missense variant (NM_000709...

Introduction: Plasma amino acids profiling can aid in the screening and diagnosis of aminoacidopathies. The goal of the current study was to analyze and report the metabolic profiles of plasma amino acid (PAA) and additionally to compare PAA-reference intervals (RI) from Pakistan with more countries utilizing Clinical Laboratory Integrated Reports (CLIR). Methods: This was a cross sectional prospective single center study. Twenty-two amino acids were analyzed in each sample received for one year at the clinical laboratory ...

AIM: There are no recommended guidelines or clinical studies on safety of COVID-19 vaccines in patients with inborn errors of metabolism (IEMs). Here, we aimed to examine the relationship between COVID-19 vaccination and metabolic outcome in paediatric IEM patients. METHODS: Patients with IEM between the ages of 12 and 18 were enrolled. Term metabolic decompensation was defined as acute disruption in metabolic homeostasis due to vaccination. Clinical and biochemical markers were compared between pre- and post-vaccination periods...

Advances in data acquisition via high resolution genomic, transcriptomic, proteomic and metabolomic platforms have driven the discovery of the underlying factors associated with metabolic disorders (MD) and led to interventions that target the underlying genetic causes as well as lifestyle changes and dietary regulation. The review focuses on fourteen of the most widely studied inherited MD, which are familial hypercholesterolemia, Gaucher disease, Hunter syndrome, Krabbe disease, Maple syrup urine disease, Metachromatic leukodystrophy, Mitochondrial encephalopathy lactic acidosis stroke-like episodes (MELAS), Niemann-Pick disease, Phenylketonuria (PKU), Porphyria, Tay-Sachs disease, Wilson's disease, Familial hypertriglyceridemia (F-HTG) and Galactosemia based on genome wide association studies, epigenetic factors, transcript regulation, post-translational genetic modifications and biomarker discovery through metabolomic studies...

Maple Syrup Urine Disease (MSUD) is a metabolic disorder characterized by high levels in blood and urine of branched-chain amino acids leucine, isoleucine, and valine and their alpha-ketoacids, by a partial or total blockade in the activity of branched-chain complex alpha-keto acids dehydrogenase. The main symptoms in MSUD occur in the central nervous system, including cognitive deficits, locomotor, poor feeding, seizures, psychomotor delay, and mental retardation, but the mechanisms of neurotoxicity and behavior alteration due to this disease are poorly understood, thus this study aimed at showing the effects of leucine exposure on glutamate levels and behavior in zebrafish...

Few studies exist describing resources and care of pediatric patients with inborn errors of metabolism (IEM) admitted to pediatric intensive care unit (PICU). This study aims to characterize the PICU admissions of these patients to provide better diagnostic and therapeutic care in the future. Retrospective analysis of pediatric patients with IEM admitted to the PICU of a tertiary care center at a metabolic referral university hospital from 2009 to 2019 was included. Clinical information and demographic data were collected from PICU clinical records...

Branched-chain amino acids (BCAAs), composed of leucine, isoleucine, and valine, are important essential amino acids in human physiology. Decades of studies have revealed their roles in protein synthesis, regulating neurotransmitter synthesis, and the mechanistic target of rapamycin (mTOR). BCAAs are found to be related to many metabolic disorders, such as insulin resistance, obesity, and heart failure. Also, many diseases are related to the alteration of the BCAA catabolism enzyme branched-chain α-keto acid dehydrogenase kinase (BCKDK), including maple syrup urine disease, human autism with epilepsy, and so on...

Most state newborn screening programs in the U.S. currently contribute case data to the Newborn Screening Technical Assistance and Evaluation Program (NewSTEPs). To assess the usability of these data for research, we examined the completeness of key variables, particularly race and ethnicity. Data included 24,129 cases of 34 newborn screening disorders from 45 states available in NewSTEPs as of 31 August 2020. Birth years of cases ranged between 2006 and 2020. Rates of missing data for sex, gestational age, birth weight, and race/ethnicity were 3...

Maple syrup urine disease (MSUD) is an intoxication-type inherited metabolic disorder in which hyperleucinemia leads to brain swelling and death without treatment. MSUD is caused by branched-chain alpha-ketoacid dehydrogenase deficiency due to biallelic loss of the protein products from the genes BCKDHA, BCKDHB, or DBT, while a distinct but related condition is caused by loss of DLD. In this case series, eleven individuals with MSUD caused by two pathogenic variants in DBT are presented. All eleven individuals have a deletion of exon 2 (delEx2, NM_001918...

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disease resulting in impaired or absent breakdown of branched-chain amino acids (BCAA) valine, isoleucine, and leucine. Classic MSUD often presents in post-natal periods, at times before newborn screening results, and is treated with a protein restricted diet supplemented with medical food and close follow up to prevent toxic buildup of blood leucine. Acute episodes of decompensation are prevented by early recognition and treatment. Acute episodes of metabolic decompensation in patients with MSUD are medical emergencies that require immediate treatments as cerebral edema may lead to brain-stem compression resulting in death...