Maple syrup urine disease: Favourable effect of early diagnosis by newborn screening on the neonatal course of the disease

Simon, Éva; Fingerhut, Ralph; Baumkötter, J.; Konstantopoulou, Vassiliki; Ratschmann, Rene; Wendel, U.

doi:10.1007/s10545-006-0315-y

Cited by 73 publications

(49 citation statements)

References 10 publications

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“…Early diagnosis by the expanded newborn screening programme using Tandem Mass Spectrometry (TMS) in the developed countries followed by early intervention during the presymptomatic or early symptomatic period have been shown to improve the outcome of patients with MSUD (Simon et al 2006;Yoon et al 2003;Heldt et al 2005). This should probably be the way forward for our country.…”

Section: Discussionmentioning

confidence: 99%

Clinical and Biochemical Profiles of Maple Syrup Urine Disease in Malaysian Children

et al. 2011

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Introduction: Maple Syrup Urine Disease (MSUD) is an autosomal recessive disorder caused by defects in the branched-chain a-ketoacid dehydrogenase complex resulting in accumulation of branched-chain amino acids (BCAAs) and corresponding branched-chain ketoacids (BCKAs) in tissues and plasma, which are neurotoxic. Early diagnosis and subsequent nutritional modification management can reduce the morbidity and mortality. Prior to 1990s, the diagnosis of MSUD and other inborn errors of metabolism (IEM) in Malaysia were merely based on clinical suspicion and qualitative one-dimensional thin layer chromatography technique. We have successfully established specific laboratory diagnostic techniques to diagnose MSUD and other IEM. We described here our experience in performing high-risk screening for IEM in Malaysia from 1999 to 2006. We analysed the clinical and biochemical profiles of 25 patients with MSUD.Methods: A total of 12,728 plasma and urine samples from patients suspected of having IEM were received from physicians all over Malaysia. Plasma amino acids quantitation using fully automated amino acid analyzer and identification of urinary organic acids using Gas Chromatography Mass Spectrometry (GCMS). Patients' clinical information were obtained from the request forms and case records Results: Twenty-five patients were diagnosed MSUD. Nineteen patients (76%) were affected by classical MSUD, whereas six patients had non-classical MSUD. Delayed diagnosis was common among our case series, and 80% of patients had survived with treatment with mild-to-moderate learning difficulties.Conclusion: Our findings suggested that MSUD is not uncommon in Malaysia especially among the Malay and early laboratory diagnosis is crucial.

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Section: Discussionmentioning

confidence: 99%

Clinical and Biochemical Profiles of Maple Syrup Urine Disease in Malaysian Children

et al. 2011

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“…The TaqMan assay is also much faster than the PCR-RFLP assay, reducing diagnostic time from 12 to 4-5 h. As prenatal testing is not an option in this population and the majority of Missouri Old Order Mennonites do not drive yet live in communities removed from major medical centers, it is often several hours after the birth before samples arrive for testing. As our goal is to diagnose MSUD in an affected infant within 24 h of birth, time is of the essence as the earlier an affected infant is put on a protein-restricted diet, the lower the blood levels of ketoacids and the better the prognosis (Edelmann et al, 2001;Mitsubuchi et al, 2005;Simon et al, 2006;Packman et al, 2007). Additionally, there are more than 7,000 real-time PCR machines in circulation in North America capable of performing the TaqMan assay, with about 300 of those in clinical settings (Applied Biosystems; personal communication).…”

Section: Discussionmentioning

confidence: 99%

DNA Carrier Testing and Newborn Screening for Maple Syrup Urine Disease in Old Order Mennonite Communities

Carleton

Peck

Grasela

et al. 2010

Genetic Testing and Molecular Biomarkers

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Maple syrup urine disease (MSUD) is an inherited metabolic disorder caused by mutations in the branched chain a-keto acid dehydrogenase complex. Worldwide incidence of MSUD is 1:225,000 live births. However, within Old Order Mennonite communities, the incidence is 1:150 live births and results from a common tyrosine to asparagine substitution (Y438N) in the E1a subunit of branched chain a-keto acid dehydrogenase. We developed a new DNA diagnostic assay utilizing TaqMan Ò technology and compared its efficacy, sensitivity, and duration with an existing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Carrier testing was performed by both TaqMan technology and PCR-RFLP on DNA isolated from buccal swabs of 160 individuals as well as from buccal swabs and blood spots of nine at-risk newborns; assay time, sensitivity, and reliability were also evaluated. The TaqMan assay, like the PCR-RFLP assay, accurately determined Y438N E1a allele status. However, the TaqMan assay appeared (1) more sensitive than the PCR-RFLP assay, requiring 10-fold less DNA (10 ng) to reliably determine genotype status and (2) faster, reducing the assay time required for diagnosis from *12 to 5 h. TaqMan technology allowed more rapid DNA diagnoses of MSUD in the neonate, thereby reducing the likelihood of neurological impairment while enhancing health and prognosis for affected infants.

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“…Neonatal presentation with poor feeding, vomiting, lethargy and abnormal movements (rhythmic boxing and cycling movements of the limbs), fluctuating ophthalmoplegia, and seizures is quite common [8]. Early detection is critical, as initiation of therapy within the first 5 days may be associated with near normal cognitive outcome [12]. The diagnosis is suggested by the odor of maple syrup or burnt sugar in cerumen at 24 to 48 hours of life or in urine during the latter part of the first week and is confirmed by detecting increased values of BCAAs and BCKAs in blood and urine (2,8).…”

Section: Maple Syrup Urine Diseasementioning

confidence: 99%

Neonatal Seizures and Inborn Errors of Metabolism: An Update

Parisi¹,

Nicotera²,

Alagna³

et al. 2015

Int J Pediatr Neonat Care

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Early identification of an underlying inborn error of metabolism in newborns with otherwise unexplained seizures may address appropriate disease-specific treatment and provide important tools about the choice of the antiepileptic drugs.Neonatal seizures usually present as prolonged or recurrent, often configuring epileptic status. Striking features of an underlying metabolic disorder include abnormal neurological examination, lethargy and/ or symptoms of acute decompensation.Ex adiuvantibus, trial with intravenous pyridoxine administration could be attempted in refractory unexplained neonatal seizures. Peculiar EEG patterns such as Suppression Burst may address diagnosis and laboratory work-up being most frequently associated to specific metabolic disorders.

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Maple syrup urine disease: Favourable effect of early diagnosis by newborn screening on the neonatal course of the disease

Abstract: After diagnosis in screening, treatment can be initiated before the occurrence of severe metabolic decompensation. However, a favourable effect can only be achieved with immediate transfer of the neonate to a metabolic centre for adequate treatment in case of a positive screening result.

Cited by 73 publications

References 10 publications

Clinical and Biochemical Profiles of Maple Syrup Urine Disease in Malaysian Children

Clinical and Biochemical Profiles of Maple Syrup Urine Disease in Malaysian Children

DNA Carrier Testing and Newborn Screening for Maple Syrup Urine Disease in Old Order Mennonite Communities

Neonatal Seizures and Inborn Errors of Metabolism: An Update

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