Acute Lymphoblastic Leukemia in Combined Methylmalonic Acidemia and Homocysteinemia (cblC Type): A Case Report and Literature Review
Background: Methylmalonic acidemia (MMA) can display many clinical manifestations, among which acute lymphoblastic leukemia (ALL) has not been reported, and congenital heart disease (CHD) is also rare.Case presentation: We report an MMA case with ALL and CHD in a 5.5-year-old girl. With developmenta...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.856552/full |
| _version_ | 1828413891179184128 |
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| author | Jun Zhu Shuisen Wan Xueqi Zhao Binlu Zhu Yuan Lv Hongkun Jiang |
| author_facet | Jun Zhu Shuisen Wan Xueqi Zhao Binlu Zhu Yuan Lv Hongkun Jiang |
| author_sort | Jun Zhu |
| collection | DOAJ |
| description | Background: Methylmalonic acidemia (MMA) can display many clinical manifestations, among which acute lymphoblastic leukemia (ALL) has not been reported, and congenital heart disease (CHD) is also rare.Case presentation: We report an MMA case with ALL and CHD in a 5.5-year-old girl. With developmental delay and local brain atrophy in MRI, she was diagnosed with cerebral palsy at 9 months old. Rehabilitation was performed since then. This time she was admitted to hospital because of weakness and widespread bleeding spots. ALL-L2 (pre-B-cell) was confirmed by bone marrow morphology and immunophenotyping. Echocardiography showed patent foramen ovale. The girl was treated with VDLD and CAML chemotherapy, during which she developed seizures, edema and renal insufficiency. Decrease of muscle strength was also found in physical examination. Screening for inherited metabolic disorders showed significantly elevated levels of methylmalonate-2, acetylcarnitine (C2), propionylcarnitine (C3), C3/C2 and homocysteine. Gene analysis revealed a compound heterozygous mutaion in MMACHC (NM_015,560): c.80A > G (p.Gln27Arg) and c.609G > A (p.Trp203*). CblC type MMA was diagnosed. Intramuscular injection of cyanocobalamin and intravenous L-carnitine treatment were applied. The edema vanished gradually, and chemotherapy of small dosage of vindesine was given intermittently when condition permitted. 2 months later, muscle strength of both lower limbs were significantly improved to nearly grade 5. The levels of methylmalonic acid and homocysteine were improved.Conclusion: Metabolic disease screening and gene analysis are very necessary for diseases with complex clinical symptoms. ALL can be a rare manifestation for MMA.Synopsis: We report a case of methylmalonic acidemia with acute lymphoblastic leukemia and congenital heart disease, which uncovered the importance of genetic testing and metabolic diseases screening in patients with multiple systemic organ involvement. |
| first_indexed | 2024-12-10T13:16:46Z |
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| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-10T13:16:46Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-8f6f7a3209ff4045a1f16b91b9a9ec952022-12-22T01:47:30ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-04-011310.3389/fgene.2022.856552856552Acute Lymphoblastic Leukemia in Combined Methylmalonic Acidemia and Homocysteinemia (cblC Type): A Case Report and Literature ReviewJun Zhu0Shuisen Wan1Xueqi Zhao2Binlu Zhu3Yuan Lv4Hongkun Jiang5Department of Pediatrics, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Pediatrics, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Pediatrics, The First Hospital of China Medical University, Shenyang, ChinaDepartment of Pediatrics, West China Second University Hospital, Chengdu, ChinaDepartment of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Pediatrics, The First Hospital of China Medical University, Shenyang, ChinaBackground: Methylmalonic acidemia (MMA) can display many clinical manifestations, among which acute lymphoblastic leukemia (ALL) has not been reported, and congenital heart disease (CHD) is also rare.Case presentation: We report an MMA case with ALL and CHD in a 5.5-year-old girl. With developmental delay and local brain atrophy in MRI, she was diagnosed with cerebral palsy at 9 months old. Rehabilitation was performed since then. This time she was admitted to hospital because of weakness and widespread bleeding spots. ALL-L2 (pre-B-cell) was confirmed by bone marrow morphology and immunophenotyping. Echocardiography showed patent foramen ovale. The girl was treated with VDLD and CAML chemotherapy, during which she developed seizures, edema and renal insufficiency. Decrease of muscle strength was also found in physical examination. Screening for inherited metabolic disorders showed significantly elevated levels of methylmalonate-2, acetylcarnitine (C2), propionylcarnitine (C3), C3/C2 and homocysteine. Gene analysis revealed a compound heterozygous mutaion in MMACHC (NM_015,560): c.80A > G (p.Gln27Arg) and c.609G > A (p.Trp203*). CblC type MMA was diagnosed. Intramuscular injection of cyanocobalamin and intravenous L-carnitine treatment were applied. The edema vanished gradually, and chemotherapy of small dosage of vindesine was given intermittently when condition permitted. 2 months later, muscle strength of both lower limbs were significantly improved to nearly grade 5. The levels of methylmalonic acid and homocysteine were improved.Conclusion: Metabolic disease screening and gene analysis are very necessary for diseases with complex clinical symptoms. ALL can be a rare manifestation for MMA.Synopsis: We report a case of methylmalonic acidemia with acute lymphoblastic leukemia and congenital heart disease, which uncovered the importance of genetic testing and metabolic diseases screening in patients with multiple systemic organ involvement.https://www.frontiersin.org/articles/10.3389/fgene.2022.856552/fullmethylmalonic acidemiaacute lymphoblastic leukemiacongenital heart diseaseshomocysteinemiagenetic analysis |
| spellingShingle | Jun Zhu Shuisen Wan Xueqi Zhao Binlu Zhu Yuan Lv Hongkun Jiang Acute Lymphoblastic Leukemia in Combined Methylmalonic Acidemia and Homocysteinemia (cblC Type): A Case Report and Literature Review Frontiers in Genetics methylmalonic acidemia acute lymphoblastic leukemia congenital heart diseases homocysteinemia genetic analysis |
| title | Acute Lymphoblastic Leukemia in Combined Methylmalonic Acidemia and Homocysteinemia (cblC Type): A Case Report and Literature Review |
| title_full | Acute Lymphoblastic Leukemia in Combined Methylmalonic Acidemia and Homocysteinemia (cblC Type): A Case Report and Literature Review |
| title_fullStr | Acute Lymphoblastic Leukemia in Combined Methylmalonic Acidemia and Homocysteinemia (cblC Type): A Case Report and Literature Review |
| title_full_unstemmed | Acute Lymphoblastic Leukemia in Combined Methylmalonic Acidemia and Homocysteinemia (cblC Type): A Case Report and Literature Review |
| title_short | Acute Lymphoblastic Leukemia in Combined Methylmalonic Acidemia and Homocysteinemia (cblC Type): A Case Report and Literature Review |
| title_sort | acute lymphoblastic leukemia in combined methylmalonic acidemia and homocysteinemia cblc type a case report and literature review |
| topic | methylmalonic acidemia acute lymphoblastic leukemia congenital heart diseases homocysteinemia genetic analysis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.856552/full |
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