Name: Bing-Juan Han ( ) profession : Pediatrician Department: - PowerPoint PPT Presentation

Name: Bing-Juan Han ( 韩炳娟 ) profession : Pediatrician Department: Neonatal disease screening centre of Jinan Maternity and children care Hospital, Jinan, China. Work Address: Jianguo Small Jingsan Road 2#, Jinan City, Shandong Province, China, 250001. Tel of Office: 86-0531-8902-9714 Tel: 86-1805-3153-851 Email: hbj208@163.com

Clinical presentation, gene analysis and outcomes in young patients with early-treated combined methylmalonic acidemia and homocysteinemia (cblC type) in Shandong province, China Bing-Juan Han Jinan Maternity and Children Care Hospital, Shandong Province, China

Outline Backgrounds Results Methods Conclusion

Backgrounds Italian ： German： 1:115,000 1:169,000 incidence of MMA ranges New York from 1:48,000 to 1:250,000 1:100,000 Taiwan： 1:85,000 Beijing Japan： and 1:50,000 Shanghai1: 26,000

Backgrounds combined MMA and homocysteinemia 70% Isolated MMA 80% is cblC type

Objectives • To estimate the incidence of MMA on newborn screening in Shandong province • summarize the clinical presentation, biochemical features, mutation analysis, and treatment regime of early-treated patients with cblC disease.

Methods • 35,291 newborns were screened for MMA. • The levels of C3, C3/C2, methionine and tHcy were measured. • Most patients received treatment with intramuscular hydroxocobalamin after diagnosis. Metabolic parameters, clinical presentation and • mental development were followed up.

Results

Results

Results

Results

Results Nine patients were identified among 35,291 by newborn screening, giving an • estimated incidence of 1: 3,920 live births for MMA. MMACHC mutations were found in all the nine patients. As shown in Table 1, • 7 different mutations were identified, including c.609G>A, c.455_457delCCC, c.394C>T, c.445_446insA, c.658_660delAAG, c.452A>G and IVS1+1G>A. The mutations (c.455_457delCCC and IVS1+1G>A) are novel. • Five patients who received treatment had favorable metabolic response, with • both reduction of urine MMA and tHcy and increase of methionine. We obtained 7 records of DQ assessment. The five patients who received • treatment presented with developmental delay and obvious neurological manifestations. In two patients who did not receive any treatment, case 8 presented with severe mental retardation and developmental delay, while case 9 had nearly normal DQ values at the age of 1 1/12 years.

Conclusion • Our study characterized variable phenotypes of neurodevelopment in early-treated cblC patients diagnosed on newborn screening. • The long-term outcomes of cblC disease are unsatisfactory in spite of conventional treatment and improvement of biochemical abnormalities. Although the number of patients is too small, the information • provided in this work is of value in highlighting possible genotype-phenotype correlation that influences outcomes in cblC disease by future studies.

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