BACKGROUND AND OBJECTIVES

Diet compliance is critical in managing Maple Syrup Urine Disease (MSUD) to prevent physiological and neurological damage. However, there is a lack of studies looking at factors critical to diet compliance. This study determined the caregivers’ nutrition knowledge, attitudes, and feeding practices (KAP); and its relationship to Filipino MSUD children’s leucine level, nutritional status, and nutrient intake.

METHODS

A cross-sectional, sequential explanatory research approach using survey was utilized. Data tools were questionnaires and food records.

RESULTS

The participants were 20 caregivers and 21 MSUD children (aged 6 to 83 months). Caregivers had moderately high feeding practices and knowledge scores and had positive attitudes towards providing adequate nutritional care; still, they were struggling with diet compliance.

Their nutrition knowledge was related to their attitude (p-value: 0.021), feeding practices (p-value: 0.037), and their children’s weight-for-age (p-value: 0.036). Furthermore, knowledge and feeding practices were related to the children’s natural-protein status (p-value: 0.043 and 0.006, respectively). The caregivers’ sex was related to the children’s leucine (p-value=0.010), those with female caregivers had lower leucine by 470 μmol/L on average. Moreover, children with good leucine control belonged to higher-income households (p-value=0.049).

CONCLUSION

With caregiver's nutrition knowledge having been possibly associated with the children’s weight-forage, and their knowledge and feeding practices with the children's natural protein status, as well as knowledge positively affecting both attitude and feeding practice, interventions for improving all caregivers’ nutrition knowledge and feeding practices are recommended. Additionally, with caregivers’ sex and income having been found to be related to metabolic control, it is suggested that strategies to better manage these barriers be carried out. These may include improving support for male caregivers, with children under their care having higher leucine than those cared for by their female counterparts. Added provisions may likewise be planned for further reducing the impact of income-related barriers.

Human ; Caregivers ; Attitude ; Maple Syrup Urine Disease ; Child ; Children

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient with dihydrolipoamide dehydrogenase deficiency. METHODS: Potential variants of the DLD gene were detected by whole exome sequencing and verified by Sanger sequencing. RESULTS: Compound heterozygous variants, c.704_705delTT (p.Leu235Argfs*8) and c.1058T>C (p.Ile353Thr), were detected in the DLD gene. The c.1058T>C (p.Ile353Thr) variant was derived from his mother and known to be pathogenic. The c.704_705delTT (p.Leu235Argfs*8) variant was derived from his father and was unreported previously. CONCLUSION The compound heterozygous variants of c.704_705delTT (p.Leu235Argfs*8) and c.1058T>C (p.Ile353Thr) of the DLD gene probably underlay the disease in this patient. Above finding has facilitated genetic counseling and prenatal diagnosis for the family.
Acidosis, Lactic/genetics* ; Dihydrolipoamide Dehydrogenase/genetics* ; Female ; Genetic Testing ; Genetic Variation ; Humans ; Male ; Maple Syrup Urine Disease/genetics* ; Pregnancy ; Whole Exome Sequencing

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

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 ; Neonatal Screening

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) ; genetics ; Humans ; Maple Syrup Urine Disease ; diagnosis ; genetics ; therapy ; Mutation

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

External quality assessment (EQA) trials of conventional newborn screening tests for phenylketonuria, galactosemia, congenital adrenal hyperplasia, maple syrup urine disease, homocystinuria, and congenital hypothyroidism, as well as extended newborn screening tests using tandem mass spectrometry, were performed twice in 2016 and 2017. A total of 44 specimens in the form of dried blood spots were distributed in each trial to 16 laboratories. The response rate of these laboratories was 100%. The mean, standard deviation, coefficient of variation, median, and cut-offs were evaluated for each analyte in the newborn screening tests. EQA trials for the analyses of methylmalonic acid, vanillylmandelic acid, catecholamines, metanephrines, organic acids, and amino acids were also performed. A well-designed EQA program and continuous education would improve the performance of metabolite testing.
Adrenal Hyperplasia, Congenital ; Amino Acids ; Catecholamines ; Congenital Hypothyroidism ; Education ; Galactosemias ; Homocystinuria ; Humans ; Infant, Newborn ; Korea* ; Maple Syrup Urine Disease ; Mass Screening ; Methylmalonic Acid ; Phenylketonurias ; Tandem Mass Spectrometry ; Vanilmandelic Acid

OBJECTIVETo investigate the clinical features of one pair of twin neonates with maple syrup urine disease (MSUD) in the Chinese Han population and pathogenic mutations in related genes, and to provide guidance for the early diagnosis and treatment of MSUD.

METHODSThe clinical and imaging data of the twin neonates were collected. The peripheral blood samples were collected from the twin neonates and their parents to detect the genes related to MSUD (BCKDHA, BCKDHB, DBT, and DLD). The loci with gene mutations were identified, and a bioinformatic analysis was performed.

RESULTSTwo mutations were detected in the BCKDHB gene, missense mutation c.304G>A (p.Gly102Arg) and nonsense mutation c.331C>T (p.Arg111*), and both of them were heterozygotes. The mutation c.304G>A (p.Gly102Arg) had not been reported in the world. Their father carried the missense mutation c.304G>A (p.Gly102Arg), and their mother carried the nonsense mutation c.331C>T (p.Arg111*).

CONCLUSIONSThe c.331C>T (p.Arg111*) heterozygous mutation in BCKDHB gene is the pathogenic mutation in these twin neonates and provides a genetic and molecular basis for the clinical features of children with MSUD.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide) ; genetics ; Diseases in Twins ; Female ; Humans ; Infant, Newborn ; Male ; Maple Syrup Urine Disease ; genetics ; Mutation

Two external quality assessment (EQA) trials of conventional newborn screening tests for phenylketonuria, galactosemia, congenital adrenal hyperplasia, maple syrup urine disease, homocystinuria, and congenital hypothyroidism, as well as newborn screening tests using tandem mass spectrometry, were performed in 2015. A total of 44 specimens in the form of dried blood spots were distributed to 16 laboratories and the response rate of these laboratories was 100%. The mean, standard deviation, coefficient of variation, median, and cut-offs were evaluated for each analyte in the newborn screening tests. Two EQA trials for the analyses of methylmalonic acid, vanillylmandelic acid, catecholamines, metanephrines, organic acids, and amino acids were also performed. A well-designed EQA program and continuous education would improve the performance of biochemical genetics tests.
Adrenal Hyperplasia, Congenital ; Amino Acids ; Catecholamines ; Congenital Hypothyroidism ; Education ; Galactosemias ; Homocystinuria ; Humans ; Infant, Newborn ; Korea* ; Maple Syrup Urine Disease ; Mass Screening ; Methylmalonic Acid ; Molecular Biology* ; Phenylketonurias ; Tandem Mass Spectrometry ; Vanilmandelic Acid

Two trials of external quality assessment (EQA) of conventional newborn screening tests for phenylketonuria, galactosaemia, congenital adrenal hyperplasia, maple syrup urine disease, homocystinuria, and congenital hypothyroidism, as well as newborn screening tests were performed using tandem mass spectrometry in 2014. A total of 39 specimens in the form of dried blood spots were distributed to 16 laboratories and the response rate of these laboratories was 100%. Screening tests for phenylketonuria and congenital hypothyroidism did not meet the accepted performance criteria in some laboratories. The mean, standard deviation, coefficient of variation, median, and cut-offs were evaluated for each analyte in the newborn screening tests. Two trials of EQA for the analyses of methylmalonic acid, vanillylmandelic acid, catecholamines, metanephrines, organic acids, and amino acids were also performed. A well-designed EQA program and continuous education would improve the performance of biochemical genetic testing.
Adrenal Hyperplasia, Congenital ; Amino Acids ; Catecholamines ; Congenital Hypothyroidism ; Education ; Homocystinuria ; Humans ; Infant, Newborn ; Korea ; Maple Syrup Urine Disease ; Mass Screening ; Methylmalonic Acid ; Molecular Biology* ; Phenylketonurias ; Tandem Mass Spectrometry ; Vanilmandelic Acid