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

Bing-Juan Han

Jinan Maternity and Children Care Hospital, Shandong Province, China

Clinical presentation, gene analysis and outcomes in young patients with early-treated combined methylmalonic acidemia and homocysteinemia (cblC type) in Shandong province, China

Outline

Backgrounds Methods Results Conclusion

Backgrounds

incidence of MMA ranges from 1:48,000 to 1:250,000

German： 1:169,000 Italian： 1:115,000 New York 1:100,000 Beijing and Shanghai1: 26,000 Japan： 1:50,000 Taiwan： 1:85,000

70%

combined MMA and homocysteinemia Isolated MMA 80% is cblC type

Backgrounds

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 11/12years.

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.

Our Team

Thanks for your attention