Humans ; Infant, Newborn ; Metabolism, Inborn Errors ; diagnosis ; therapy

OBJECTIVEMany inborn errors of metabolism have similar presenting clinical manifestations, making early diagnosis difficult. We report our experience with tandem mass spectrometry combined with urine gas chromatography/mass spectrometry as a means of definitively diagnosing inborn errors of metabolism.

METHODSOne hundred and thirty-two children with suspected inborn errors of metabolism but without specific clinical manifestations, admitted to the Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine between June 1, 2003 and September 30, 2006, were studied. Children received routine biochemical examinations, as well as mass spectrometry and gas chromatography-mass spectrometry.

RESULTSFifteen cases (11.5%) were confirmed as having inborn errors of metabolism, including 6 cases of methylmalonic acidemia, 2 of propionic academia, 2 of Type II citrullinemia, 1 of biotinidase deficiency, 1 of tyrosinemia, 1 of maple syrup urine disease, 1 of omithine transcarbamylase deficiency and 1 of very long chain Acyl CoA dehydrogenase deficiency.

CONCLUSIONSThe combined use of tandem mass spectrometry with urine gas chromatography mass spectrometry is useful for early diagnosis of inborn errors of metabolism in children with suspected inborn errors of metabolism but without specific clinical manifestations.

Amino Acid Metabolism, Inborn Errors ; diagnosis ; Child ; Child, Preschool ; Female ; Gas Chromatography-Mass Spectrometry ; methods ; Humans ; Infant ; Infant, Newborn ; Lipid Metabolism, Inborn Errors ; diagnosis ; Male ; Metabolism, Inborn Errors ; diagnosis ; urine ; Tandem Mass Spectrometry ; methods

Elevated propionyl C3 carnitine is the most common abnormality seen in tandem mass spectrometry newborn screening profiles, with an incidence of 0.15% seen in our South Australian newborn screening programme. The most common cause for this result in our population is vitamin B12 deficiency but differential diagnoses include the inherited disorders of propionic and methylmalonic acid metabolism and cobalamin deficiencies. An approach to confirmatory testing and subsequent management of infants with elevated propionic carnitine is presented.
Humans ; Infant, Newborn ; Metabolism, Inborn Errors ; diagnosis ; Neonatal Screening ; Vitamin B 12 ; metabolism

Carnitine is necessary for transport of long-chain fatty acids into mitochondria, to enter the beta-oxidation cycle. Four carnitine cycle defects have been described. The carnitine transporter mediates carnitine transport across the plasma membrane. Symptoms include hypoketotic hypoglycaemia and cardiomyopathy. Some affected subjects are asymptomatic. Newborn screening detects very low levels of free carnitine in some but not all. Carnitine palmitoyltransferase type IA (CPTI) transports long-chain fatty acyl-CoAs across the outer mitochondrial membrane. Affected infants have hypoketotic hypoglycaemia with catabolic stress, but otherwise remain well. Newborn screening tests reveal elevated free carnitine, (elevated C0/C16+C18). Sensitivity is unclear and confirmation needs leukocyte or fibroblast assays. Carnitine-acylcarnitine translocase transfers fatty acylcarnitines across the inner mitochondrial membrane. The most common presentation is sudden death in the first days. Carnitine palmitoyltransferase type II (CPTII) converts long-chain acylcarnitines to long-chain acylCoAs for beta-oxidation. Severe deficiency is lethal. Newborn screening for both disorders reveals elevated palmitoylcarnitine and enzymology or mutation analysis is needed for diagnosis. Late-onset CPTII is the most common disorder, presenting as muscle pain and rhabdomyolysis on severe exercise. All 4 disorders can be detected by newborn screening, with variable sensitivity. Late-onset CPTII probably cannot be detected. Carnitine transporter, CPTI and late-onset CPTII have proven treatment strategies.
Carnitine ; metabolism ; Carnitine O-Palmitoyltransferase ; deficiency ; Humans ; Infant, Newborn ; Metabolism, Inborn Errors ; diagnosis ; enzymology ; Neonatal Screening

China ; Humans ; Infant, Newborn ; Metabolism, Inborn Errors ; diagnosis ; therapy ; Neonatal Screening ; Phenylketonurias ; diagnosis ; Tandem Mass Spectrometry

Adolescent ; Female ; Humans ; Lipid Metabolism, Inborn Errors ; diagnosis ; therapy ; Muscular Diseases ; diagnosis ; therapy

This study aimed to identify the type of carnitine palmitoyltransferase 2 (CPT2) gene mutation in the child with carnitine palmitoyltransferase II (CPT II) deficiency and her parents and to provide the genetic counseling and prenatal diagnosis for the family members. As the proband, a 3-month-old female baby was admitted to the hospital due to fever which had lasted for 8 hours. Tandem mass spectrometric analysis for blood showed an elevated plasma level of acylcarnitine, which suggested CPT II deficiency. The genomic DNA was extracted from peripheral blood of the patient and her parents. Five exon coding regions and some intron regions at the exon/intron boundaries of the CPT2 gene were analyzed by PCR and Sanger sequencing. Amniotic fluid was taken from the mother during the second trimester, and DNA was extracted to analyze the type of CPT2 gene mutation. Sanger sequencing results showed that two mutations were identified in the CPT2 gene of the proband: c.886C>T (p.R296X) and c.1148T>A (p.F383Y), which were inherited from the parents; the second child of the mother inherited the mutation of c.886C>T (p.R296X) and showed normal acylcarnitine spectrum and normal development after birth. It is concluded that the analysis of CPT2 gene mutations in the family suggested that the proband died of CPT II deficiency and that the identification of the mutations was helpful in prenatal diagnosis in the second pregnancy.
Carnitine O-Palmitoyltransferase ; deficiency ; genetics ; Female ; Humans ; Infant ; Metabolism, Inborn Errors ; diagnosis ; genetics ; Mutation ; Prenatal Diagnosis

The study of inherited metabolic disorders (IMD) in Thailand is in its infancy when compare with developed countries. Prior to 1987, majority of these disorders were clinically diagnosed since there were only a handful of clinicians and scientists with expertise in inborn errors of metabolism, lack of well-equipped laboratory facilities and government support. In developing countries, inherited metabolic disorders are not considered a priority due to the prevalence of infectious diseases such as HIV infection and congenital infections. A multicentre survey conducted in 1994 and 2001 revealed the existence of numerous cases of IMD from all over the country. Case reports and publications on IMD in Thai (and international) medical journals in past 20 years had undoubtedly raised its awareness among Thai paediatricians and scientists. In 2001, the Genetic Metabolic Centre was first established in Siriraj Hospital Faculty of Medicine, Thailand. Numerous new cases of IMD had been identified since then.
Child ; Humans ; Metabolism, Inborn Errors ; diagnosis ; epidemiology ; genetics ; Thailand ; Time Factors

Inborn errors of metabolism constitute an important cause of neurological disease in the neonatal period and can present clinically as encephalopathy. Although it is relatively rare, it is important to have a high index of suspicion. Appropriate investigations and a step-wise approach to diagnosis allow for early institution of treatment and can prevent significant morbidity and mortality. The aim of this article is to give a brief outline of the various inborn errors of metabolism to consider in neonatal encephalopathy and to provide a framework for investigation and diagnosis.
Brain Diseases, Metabolic ; etiology ; Humans ; Infant, Newborn ; Metabolism, Inborn Errors ; complications ; diagnosis

Female ; Gas Chromatography-Mass Spectrometry ; Humans ; Infant, Newborn ; Male ; Metabolism, Inborn Errors ; diagnosis ; Neonatal Screening