1.Gaps in the newborn screening process: Using maple syrup urine disease as a case
Mary Ann R. Abacan ; Sylvia C. Estrada ; Leniza G. de Castro-Hamoy ; Mary Anne D. Chiong
Acta Medica Philippina 2020;54(4):423-427
Saving babies from mental retardation and death is the aim of the newborn screening program. A complex process of sample collection, processing and feedback is undertaken before reaching this goal. As with other systems, the newborn screening program is not perfect and periodic review is needed to continually improve services. Using maple syrup urine disease (which is the most common inborn error of metabolism detected through newborn screening) as an index case, this paper aims to present the gaps in diagnosis and management by citing cases and providing a commentary.
Maple Syrup Urine Disease
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Neonatal Screening
2.Maple syrup urine disease in a neonate.
Ya LING ; Yan QIAN ; Xiu-Lan PENG ; Kai WANG ; Jie-Jin GAO ; Ai-Qin XU
Chinese Journal of Contemporary Pediatrics 2009;11(11):945-946
3.A 1-year-old female with maple syrup urine disease presenting with acrodermatitis-enteropathica-like lesions.
Rona Maria R. ABAD ; Johanna Pauline H. LAZO-DIZON
Acta Medica Philippina 2018;52(61):575-580
A 1-year-old female with maple syrup urine disease presenting with erythematous, partially eroded plaques on the trunk, anogenital area, and extremities experienced metabolic crisis. The skin lesions appeared at 11 months of age and was thought to result from amino acid imbalance secondary to erratic supplementation of specialized milk formula devoid of isoleucine, leucine, and valine. Serial urine monitoring showed persistent ketones and elevated serum leucine and valine. The patient was managed with emollients, intralipid 20%, and addition of isoleucine and valine supplements to counter the neurotoxic effect of leucine. After 8 days of proper feeding and continuous emollient application, the lesions improved and skin biopsy revealed superficial perivascular dermatitis. Although a decrease in erythema and desquamation was noted, the patient had persistent cerebral edema and continued to deteriorate.
Maple Syrup Urine Disease ; Isoleucine ; Leucine ; Valine ; Erythema
4.Maple syrup urine disease of neonates: report of two cases and review of literature.
Zheng CHEN ; Fang LUO ; Xiu-jing WU ; Li-Ping SHI
Chinese Journal of Pediatrics 2010;48(9):680-684
OBJECTIVETo analyze and summarize clinical manifestation of maple syrup urine disease (MSUD) of neonates.
METHODSData of two cases with neonatal MSUD and the reports of 15 cases seen in the past 15 years in China were reviewed and analyzed.
RESULTSThere was an increasing number of reports of cases with neonatal MSUD. All the 17 cases had the symptom of poor feeding between 3 h and 8 d after birth; 7 cases had family history; 14 cases showed progressive neurologic signs. Odor of maple syrup occurred in 8 cases. Blood levels of branched-chain amino acids (BCAA) significantly increased in 13 cases and 6 neonates were diagnosed using tandem mass spectrometry. Urinary levels of BCAA and metabolite elevated in 12 cases and 5 neonates were diagnosed using gas chromatography-mass spectrometry. MRI/CT demonstrated abnormal signal in 10 cases. Twelve cases died or their parents gave up treatment and one case had cerebral palsy; 4 cases were treated with BCAA-free formula milk and showed improved outcome.
CONCLUSIONNewborns with MSUD often had early appeared non-specific symptoms with poor feeding and lethargy, most cases later showed an odor resembling maple syrup and neurologic signs. For patients who were suspected of having MSUD, blood and urine concentrations of BCAA should be tested for early diagnosis. Specific MRI edema signal from brain suggests the possibility of MSUD. Early intervention and treatment after diagnosis, with compliance of parents, would improve the patient's outcome.
Amino Acids, Branched-Chain ; blood ; urine ; Humans ; Infant, Newborn ; Male ; Maple Syrup Urine Disease ; diagnosis
5.Annual Report on External Quality Assessment in Inborn Error of Metabolism in Korea (2002).
Jong Won KIM ; Kye Chol KWON ; Jeong Ho KIM ; Won Ki MIN ; Myung Soo KIM ; Hai Jin HAN ; Junghan SONG ; Soo Youn LEE ; Eun Hee LEE ; Tae Yoon CHOI
Journal of Laboratory Medicine and Quality Assurance 2003;25(1):145-155
The trial of external quality assessment for inborn error of metabolism was performed in 2002. Total 10 specimens for neonatal screening tests were distributed to 61 laboratories with a response rate of 70.5%(43/61). All the control materials were sent as filter paper forms. Each laboratory replied the test results as the screening items they were testing routinely at the reception of the specimen among PKU screening, TSH, T4 (total/free), galactosemia screen, maple syrup urine disease screen, homocytinuria screen and histidinemia screen. The mean, SD, CV, median and range were analyzed.
Galactosemias
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Infant, Newborn
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Korea*
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Maple Syrup Urine Disease
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Mass Screening
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Metabolism*
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Neonatal Screening
7.Progress of research on Maple syrup disease.
Caifei YANG ; Tao CHEN ; Xiaoguang LEI ; Yuexian LIU ; Mengyuan XU ; Dan YANG
Chinese Journal of Medical Genetics 2019;36(7):737-741
Maple syrup disease (MSUD) is a rare autosomal recessive disorder caused primarily by mutations of branched-chain keto acid dehydrogenase complex (BCKDC). BCKDC includes at least four pathogenic genes of BCKDHA, BCKDHB, DLD and DBT. The clinical manifestations of MSUD are complex, and the main symptoms at the early stage include difficulty in feeding, drowsiness, change in muscle tone and special urine flavor of maple syrup. As the disease progresses, convulsion, hypoglycemia, coma and systemic failure may occur. MSUD is easily missed or misdiagnosed during the neonatal period. This paper provides a review for recent progress made in research on MSUD including etiology, physiopathology, clinical manifestation, auxiliary examination and treatment, with a particular emphasis on genetic testing and treatment.
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
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genetics
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Humans
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Maple Syrup Urine Disease
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diagnosis
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genetics
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therapy
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Mutation
8.Clinical profiles and outcomes of the most common inherited metabolic diseases in the Philippines: A review of the National Institutes of Health - Institute of Human Genetics Metabolic Registry.
Monette R. FANER ; Mary Anne D. CHIONG
Acta Medica Philippina 2020;54(3):236-243
OBJECTIVE: This study reviewed the profiles and outcomes of patients diagnosed to have the five most common inherited metabolic diseases (IMDs) in the Metabolic Registry of the National Institutes of Health - Institute of Human Genetics (NIH-IHG) from 1999 to 2016.
METHODS: The medical records of the patients diagnosed with the following inherited metabolic diseases were reviewed: maple syrup urine disease (MSUD), galactosemia, hyperphenylalaninemias (including classical phenylketonuria, mild hyperphenylalaninemia, and pterin defects), mucopolysaccharidoses (MPS), and adrenoleukodystrophy (ALD).
RESULTS: There was a total of 567 patients with IMDs, giving a minimum estimated burden of 1.9 per 100,000 livebirths (1:51,760). Clinical presentations were similar to those reported in literature. Majority of the cases of galactosemia and hyperphenylalaninemias presented with a positive newborn screening result. The local prevalence of MSUD and MPS II were higher compared to international data, which may be explained by reported founder mutations among Filipinos. Majority of the patients with IMDs were diagnosed late leading to preventable developmental delay or intellectual disability and death. Majority of patients with MSUD (80.6%) and MPS (94.7%) had intellectual disability or developmental delay. Mortality was 50.5% among patients with MSUD and 100% among patients with adrenoleukodystrophy.
CONCLUSION: There is a diversity of IMDs present in the country. A long-term strategic plan, such as the full implementation of the National Rare Disease Act, is foreseen to improve access to comprehensive healthcare and quality of life of patients with IMDs in the country.
Human ; Metabolism, Inborn Errors ; Maple Syrup Urine Disease ; Galactosemias ; Mucopolysaccharidoses ; Adrenoleukodystrophy ; Rare Diseases
9.Acute encephalopathy due to late-onset maple syrup urine disease in a school boy.
Su-Qing QU ; Li-Cai YANG ; Zuo LUAN ; Kan DU ; Hui YANG
Chinese Journal of Contemporary Pediatrics 2012;14(3):161-164
Maple syrup urine disease is a common amino acids metabolic disease. In most patients, onset occurs in the neonatal period and infancy. In this study, the case of a school boy with acute encephalopathy due to late-onset maple syrup urine disease is summarized. The boy (8.5 years) was admitted because of acute encephalopathy after suffering from infection for two days at the age of eight and a half years. Metabolic acidosis, hyperuricemia and decreased protein level in cerebrospinal fluid were found by general laboratory tests. Magnetic resonance imaging of the brain revealed signal intensity abnormalities in the bilateral cerebellum dentate nucleus, brainstem, thalamus, putamen, caudate nucleus and cortex of the cerebral hemispheres. On T1WI and T2WI scanning, hyperintensive signal was found. Blood leucine and valine were significantly elevated. Urinary 2-hydroxy isovaleric acid, 3-hydroxybutyric acid, 2-keto isovaleric acid, and 2-keto acid also increased. Both the blood amino acid and urine organic acid profiles led to the diagnosis of maple syrup urine disease. In the acute period, the patient was treated with a large dose of vitamin B1, glucose, L-carnitine and a protein-restrict diet. The patient's condition improved significantly after five days of treatment, and he recovered completely two days later. Afterwards, treatment with vitamin B1, L-carnitine and a protein-restrict diet (1 g/kg/day) was continued. One and a half months later, blood amino acids and urine organic acids returned to normal. Magnetic resonance imaging of the brain also indicated a great improvement. It was concluded that inborn metabolic disease should be considered in the patients with an onset similar to acute encephalopathy. Early diagnosis and proper treatment can prevent brain damage and improve prognosis.
Acute Disease
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Brain Diseases
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etiology
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Child
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Humans
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Magnetic Resonance Imaging
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Male
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Maple Syrup Urine Disease
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complications
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diagnosis
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therapy
10.Annual Report on External Quality Assessment in Inborn Error of Metabolism in Korea (2004).
Junghan SONG ; Kye Chol KWON ; Jeong Ho KIM ; Jong Won KIM ; Won Ki MIN ; Soo Youn LEE ; Eun Hee LEE ; Sun Hee JUN ; Tae Yoon CHOI
Journal of Laboratory Medicine and Quality Assurance 2005;27(1):125-140
The trial of external quality assessment for inborn error of metabolism was performed twice in 2004. Total 10 specimens for the conventional newborn screening tests were distributed to 43 laboratories. The response rates were 90.7%(39/43) in first trial and 90%(36/40) in second trial. All the control materials were sent as filter paper forms. Each laboratory replied the test results as the screening items they were doing as a routine test at the reception of the specimen among PKU screening, TSH, T4 (total/free), galactosemia screen, maple syrup urine disease screen, homocytinuria screen and histidinemia screen. The mean, SD, CV, median and range were analyzed. From this trial, pilot proficiency test for newborn screening using tandem mass spectrometry (MS/MS) was also performed. Total 8 blood spots were distributed to 7 laboratories performing newborn screening using MS/MS. Participants results for amino acids & acylcarnitine and their cutoff values were analyzed.
Amino Acids
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Galactosemias
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Humans
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Infant, Newborn
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Korea*
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Maple Syrup Urine Disease
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Mass Screening
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Metabolism*
;
Tandem Mass Spectrometry