Novel mutation of methylmalonyl-CoA mutase gene in a Thai infant with methylmalonic acidemia (mut0).

Isolated methylmalonic acidemia is found in patients with mutations in the MUT gene causing partial methylmalonyl CoA mutase deficiency, mut-, or complete methylmalonyl CoA mutase deficiency, mut0. Most mut0 patients have an earlier and more severe presentation than the other groups such as mut- and cbl defect. We report a 6-month-old Thai male presenting with wide-anion gap metabolic acidosis after acute lower respiratory infection. Urine organic acids analysis demonstrated excretions of methylmalonic acid and methylcitrate, consistent with methylmalonic acidemia. He was then started on low protein diet with an appropriate metabolic formula, L-carnitine (100 mg/kg/day), and oral vitamin B12 (1 mg/day). He had only one single metabolic episode at 2 years of age. At present, he is doing well with normal growth and development. His methylmalonyl-CoA mutase activity was undetectable compatible with mut0. He was found to be homozygous for a novel IVS11-2A>G mutation causing two aberrantly spliced transcripts. The identified mutation and enzyme activity of this patient should cause severe phenotype, although, our patient has milder clinical manifestations. Therefore we hypothesize that there are other factors that may determine the clinical phenotype of mutase deficiency in the present case.

Factors influencing development of Down syndrome children in the first three years of life: Siriraj experience.

OBJECTIVE: To analyze factors influencing development of Down syndrome children in the first three years of life. MATERIAL AND METHOD: A cross-sectional study was conducted in 100 Down syndrome (DS) children attending at the Genetics clinic, Department of Pediatrics, Siriraj Hospital between January 2002 and December 2005. All individuals were three to six years of age. The data was collected from January to December 2006, including general information and factors on the child and their families. The child developmental quotient (DQ) was evaluated by Capute Scales Cognitive Adaptive Test/Clinical Linguistic & Auditory Milestones Scale (CAT/CLAMS) at three years of age. Data were analyzed by descriptive statistic and multiple linear regression with the significant level at p-value < 0. 05. RESULTS: The mean development quotient (DQ) was 63.78 +/- 11.25 (range 32-91) with the majority being mild developmental delay. The child and family factors contributing to developmental quotient (DQ) outcome were birthplace, congenital heart disease, age at the first genetic counseling, regular follow-up in the Genetics clinic, age at the first early stimulation program/speech training program, parental education/occupation, and family income. Only family income and age at the first speech-training program were found to be independently associated with developmental quotient (DQ) at the age of three years (p-value < 0.05). CONCLUSION: Down syndrome is the most common genetic cause of mental retardation. Various factors contribute to developmental quotient (DQ) outcome but the most important factors are family income and age at the first speech-training program. Therefore, Down syndrome children with the above factors should be followed-up and monitored closely for the optimal long-term outcome.

Retrospective study of patients with suspected inborn errors of metabolism at Siriraj Hospital, Bangkok, Thailand (1997-2001).

INTRODUCTION: This retrospective clinical study was carried out on patients with suspected inborn errors of metabolism (IEM) at Siriraj Hospital during 1997-2001. The authors investigated 114 patients by quantitative plasma amino acid analysis. OBJECTIVE: The objective of this study was to collect and analyze epidemiologic and specific clinical data of IEM, especially in small-molecule diseases. MATERIAL AND METHOD: All patients were categorized into 2 major groups. 1) positive diagnoses for IEM 2) negative diagnoses for IEM. The two groups were investigated, studied including statistical analysis. RESULTS: The authors found that most IEM ascertained through plasma amino acid analysis were small-molecule diseases (74.3%) and amino acid disorders consisted of the most frequent disorders. The presented data demonstrated that the ratio of positive diagnoses to all patients studied was 1:8. Epidemiological data showed there were more male than female patients. Onset of diseases occurred predominantly during the first month of age, and was rarely found after 3 years of age. There were histories of consanguinity in half of the IEM patients. The most common presenting symptom was acute metabolic encephalopathy and specific signs for small-molecule disorders included hepatomegaly, unusual urine odor, acidosis, hyperammonemia, alteration of consciousness, and ketosis/ketonuria. These signs or symptoms indicated further metabolic investigations. CONCLUSION: Comparison of the data from Thailand with other countries showed both similarities and differences to the Caucasian population. Thus, further studies in IEM are much needed for the Thai population.