ABSTRACT
OBJECTIVES: To determine the incidence and types of inborn errors of metabolism (IEMs) in high-risk children using mass spectrometry techniques. METHODS: Children considered high-risk for IEM were screened for metabolic diseases during a 3-y period. Dried blood spots and urine samples were analyzed by tandem mass spectrometry (LC-MS/MS) and gas chromatograph-mass spectrometry (GCMS). Samples with abnormal amino acids were confirmed by high-performance liquid chromatography (HPLC). RESULTS: Eight hundred and twenty-two suspected cases were evaluated; of which, 87 possible cases of IEMs were identified. Homocystinuria (n = 51) was the most common IEM detected followed by biotinidase deficiency (n = 7), glutaric aciduria type 1 (n = 7), and carnitine uptake defect (n = 6). Overall, there were 45 (51.7%) cases of organic acidemia, 31 cases (35.6%) of amino acid defect, 9 (10.3%) cases of fatty-acid oxidation disorders, and 2 (2.3%) cases of probable mitochondrial disorder. CONCLUSION: IEMs are common in India, with a hospital-based incidence of 1 in approximately 6642 among high-risk children. Screening of high-risk children by mass spectrometry techniques is a valuable strategy for early diagnosis of IEMs where universal newborn screening is not yet available.
Subject(s)
Amino Acids , Tandem Mass Spectrometry , Amino Acid Metabolism, Inborn Errors , Brain Diseases, Metabolic , Child , Chromatography, Liquid , Glutaryl-CoA Dehydrogenase/deficiency , Humans , Infant, Newborn , Neonatal Screening/methods , Pilot Projects , Tandem Mass Spectrometry/methodsABSTRACT
OBJECTIVE: Long-term therapy with phenytoin and carbamazepine is known to cause hyperhomocysteinaemia. We evaluated the prevalence of hyperhomocysteinaemia in North Indian children receiving phenytoin or carbamazepine monotherapy for >6â months duration and the effect of folic acid supplementation on plasma homocysteine. METHODS: In this cross-sectional observational study we enrolled consecutive children aged 2-12â years with epilepsy who had received phenytoin or carbamazepine monotherapy for >6â months. Plasma total homocysteine, folic acid, vitamin B12 and antiepileptic drug concentrations were measured. Healthy age- and sex-matched controls were recruited. Children with homocysteine >10.4â µmol/L received folic acid supplementation for 1â month and homocysteine and folic acid concentrations were measured after 1â month follow-up. RESULTS: A total of 112 children receiving antiepileptic monotherapy for >6â months were enrolled. Hyperhomocysteinaemia was present in 54 children (90%) receiving phenytoin, 45 children (90%) receiving carbamazepine therapy and 17 (34%) controls (p<0.05). Mean plasma homocysteine concentrations were significantly higher (18.9±10.2 vs 9.1±3â µmol/L) and serum folic acid concentrations (10.04±8.5â ng/ml vs 12.6±4.8 p<0.001) and vitamin B12 concentrations (365±155â pg/mL vs 474±332â pg/mL, p=0.02) were significantly lower in the study group compared with the control group. Duration of antiepileptic drug therapy correlated significantly with elevated homocysteine and reduced folic acid concentrations (p<0.05). Supplementation with folic acid for 1â month led to a reduction in plasma homocysteine concentrations in the study group (from 20.9±10.3â µmol/L to 14.2±8.2â µmol/L, p<0.05). CONCLUSIONS: Phenytoin or carbamazepine monotherapy for >6â months duration is associated with hyperhomocysteinaemia in 90% of North Indian children. Elevated homocysteine concentrations were normalised in these children with folic acid supplementation.