Maple syrup urine disease in Thai infants.

Maple syrup urine disease (MSUD) is a rare inborn error of metabolism, caused by a deficiency in activity of the branched chain alpha-keto acid dehydrogenase impairing the degradation of the branched-chain amino acids (leucine, isoleucine and valine). Classic MSUD usually manifests in the neonatal period with poor feeding, vomiting, lethargy, muscular hypertonicity, seizure, coma and death. Thirteen cases of classic MSUD were diagnosed from 1997-2007 at the Queen Sirikit National Institute of Child Health. All cases presented in the neonatal period. The onset of symptoms ranged from 3 to 20 days (median 8 days). The time taken to make the diagnosis ranged from 18 to 356 days (median 55 days). The diagnosis was accomplished by clinical diagnosis and confirmed by detecting abnormal levels of amino acids in the blood and organic acids in the urine. Clinical manifestations were non-specific such as poor suck, weak cry, drowsiness and seizures. Majority of cases were initially diagnosed as sepsis and/or meningitis. All patients had neurological sequelae and psychomotor retardation. This results show the need for increase awareness of metabolic disorder such as MSUD and the requirement for early detection and treatment to ensure a better outcome.

6-pyruvoyltetrahydropterin synthase deficiency two-case report.

6-Pyruvoyltetrahydropterin Synthase (PTPS) deficiency is the most common cause of hyperphenylalaninemia due to tetrahydrobiopterin deficiency. The presenting symptoms of PTPS deficiency are mental retardation, convulsions, disturbance of tone and posture, drowsiness, irritability, abnormal movements, hypersalivation, and swallowing difficulties(1-3). The authors reported the first two cases of PTPS deficiency in Thailand. Both cases were male infants who showed phenylalanine levels of 25.23 mg/dl and 23.4 mg/dl respectively. The urinary pterins analysis showed low biopterin and high neopterin. The percentage of urinary biopterin was also found to be very low. The mutation analysis of the first case revealed a point mutation of exon 4, a homozygous C to T transition at nucleotide 200 in codon 67 (T67M), and the second case showed a compound heterozygous of exon 4, C to A transition at nucleotide 200, and exon 5, C to T transition at nucleotide 259 of the PTS gene confirming that they had PTPS deficiency. Treatment was started with neurotransmitters and a low phenylalanine diet. Family carriers were detected by means of urinary pterins determination and mutation analysis.

Molecular diagnosis of Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia and feeding problems in infancy, developmental delay, hyperphagia with obesity, short stature, hypogonadism, characteristic facial appearance, and behavior problems. The diagnosis of PWS is based on clinical findings that change with age. PWS has proved to be a difficult condition to recognize with the diagnosis often being delayed until later childhood or even adulthood. Therefore, a molecular testing for PWS is needed to confirm the diagnosis. OBJECTIVE: To study the clinical features of Prader-Willi syndrome patients and confirm diagnosis by molecular testing. MATERIAL AND METHOD: Eighteen Prader-Willi syndrome patients who were diagnosed between March, 1997 and February, 2002 at the Genetic Unit, Queen Sirikit National Institute of Child Health, Bangkok. Peripheral blood lymphocytes were obtained and cultured using the standard technique for chromosome analysis. For fluorescence in situ hybridization (FISH) studies, the specific DNA probes for loci small nuclear ribonucleoprotein polypeptide N (SNRPN) were used to detect deletion. Non-deleted cases were confirmed to have PWS by methylation analysis. RESULTS: The diagnosis of eighteen PWS patients was confirmed by FISH using DNA probes for loci SNRPN demonstrating a deletion of chromosome 15q11-q13 in fourteen cases (77%). Four cases (23%) were confirmed to have PWS resulting from maternal uniparental disomy by demonstrating exclusively maternal specific DNA methylation patterns. CONCLUSION: The clinical diagnosis of PWS should be confirmed by molecular testing especially in the infancy period to avoid needless invasive diagnostic testing.

Phenylketonuria detected by the neonatal screening program in Thailand.

Neonatal screening for phenylketonuria (PKU) was introduced as a pilot project in Thailand from 1992--1995, and mass screening was started in 1996 by the Department of Medical Sciences, Ministry of Public Health. Blood samples were collected by heelprick on filter paper either at 48 hours of life or before discharge from the hospital. Elevated blood phenylalanine was identified by screening with the Guthrie method, then followed by the fluorometric method: All infants with a phenylalanine level equal to or greater than 4 mg/dl were recalled and retested using the fluorometric method and confirmed by plasma amino acid analysis and urinary pterins for tetrahydrobiopterin deficiency. A total of 1,062,676 newborns were screened from October 1992--March 2001, with 5 cases confirmed with PKU. The incidence was 1 in 212,535. All patients have been treated with low phenylalanine diet. The results of this study confirm the benefit of early detection and treatment of PKU through the screening program.