Methylmalonic Acidemia Complicated by Homocystinuria Diseases: a Report of Three Cases

Zhang, Yanan; Pi, Yalei; Xue, Yan; Li, Yuqian; Qi, Zhanjiang; Zhang, Huifeng

doi:10.1007/s12325-019-01149-4

Cited by 4 publications

(7 citation statements)

References 17 publications

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“…Continuous variables are presented as the mean ± SD, and categorical variables are presented as frequencies or proportions. To minimize the influence of age, height, weight and body mass index (BMI) were converted to a Z score using the Growth Charts UK−WHO application (version 2.0.1) with references, including the Neonatal and Infant Close Monitoring Growth Chart, the UK WHO 0-4 years' growth chart, and the UK Growth chart (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

“…To date, the associated variants have shown strong heterogeneity among races. In European countries, c.271dupA and c.276G>T were the two leading variants detected in CblC patients with isolated PAH or a combination of PAH and atypical haemolytic uraemic syndrome (aHUS) ( 6 , 10 , 41 , 42 ), while in China, c.80A>G was the leading variant detected ( 8 , 9 , 43 , 44 ). In a study including 15 MMA/HCY patients with PAH, genetic diagnosis was performed in ten patients, and all of them carried the MMACHC c.80A>G variant ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

“…The mechanism was suspected to be hyperhomocysteinaemia-related thrombotic microangiopathy (TMA), as thrombi were detected in pulmonary vessels and on renal biopsy, and homocysteine was recognized as a risk factor for arteriosclerosis and thrombosis in adults. However, there was controversy as thrombosis was not found in all patients with PAH, and some patients presented with interstitial lung disease or pulmonary vessel abnormalities ( 9 , 43 , 44 ). In our study, patient 8 was diagnosed with AHS and showed no indications of pulmonary embolism.…”

Section: Discussionmentioning

confidence: 99%

“…Profitlich et al (5) conducted a retrospective study to analyse echocardiographic data in ten CblC patients and found that half of them had structural heart defects. In some patients, the sudden onset of pulmonary arterial hypertension (PAH) or renal hypertension can be a trigger of heart failure and progress into a life-threatening event (6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

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Different Pattern of Cardiovascular Impairment in Methylmalonic Acidaemia Subtypes

et al. 2022

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Methylmalonic acidaemia (MMA) has been reported to be associated with cardiovascular involvement, especially for the combined type with homocystinuria. We have screened 80 control subjects and 99 MMA patients (23 isolated type and 76 combined type) using electrocardiograph and echocardiography. 32 cases (34%) of ECG changes were found including sinus tachycardia (n = 11), prolonged QTc interval (n = 1), I-degree atrioventricular block (n = 1), left axis deviation (n = 5) and T wave change (n = 14). By echocardiography, 8 cases of congenital heart disease were found in 4 combined MMA patients (5.3%) including ventricular septal defect (n = 2), atrial septal defect (n = 3), patent ductus arteriosus (n = 1) and coronary artery-pulmonary artery fistula (n =2). Pulmonary hypertension (n = 2) and hypertrophic cardiomyopathy (n = 1) in combined subtype were also noted. Moreover, echocardiographic parameters were analyzed by multiple regression to clarify the influence of different subtypes on cardiac function. It was found that the left ventricular mass index (LVMI) was significantly reduced only in combined subtype [R = −3.0, 95%CI (−5.4, −0.5), P = 0.017]. For left ventricle, the mitral E' velocity was significantly reduced [isolated type: R = −1.8, 95%CI (−3.3, −0.4), P = 0.016; combined type: R = −2.5, 95%CI (−3.5, −1.5), P < 0.001], the global longitudinal strain (GLS) was the same [isolated type: R = −1.4, 95%CI (−2.3, −0.4), P = 0.007; Combined type: R = −1.1, 95%CI (−1.8, −0.4), P = 0.001], suggesting weakened left ventricular diastolic and systolic functions in both subtypes. For right ventricle, only in combined subtype, the tricuspid E' velocity was significantly reduced [R = −1.4, 95%CI (−2.6, −0.2), P = 0.021], and the tricuspid annular plane systolic excursion (TAPSE) was the same [R = −1.3, 95%CI (−2.3, −0.3), P=0.013], suggesting impaired right ventricular systolic and diastolic function. In conclusion, isolated and combined types showed different pattern of cardiac dysfunction, specifically the former only affected the left ventricle while the latter affected both ventricles. And it is necessary to perform echocardiographic screening and follow up in both MMA subtypes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Different Pattern of Cardiovascular Impairment in Methylmalonic Acidaemia Subtypes

et al. 2022

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“…In MMA cases combined with heart disease ( Table 1 ), ( Andersson et al, 1999 ; Heinemann et al, 2001 ; Tomaske et al, 2001 ; De Bie et al, 2009 ; Profitlich et al, 2009 ), cardiomyopathy(1.2–2.9%) and pulmonary hypertension (0.9–1.7%) were more common ( Andersson et al, 1999 ; Heinemann et al, 2001 ; Tomaske et al, 2001 ; De Bie et al, 2009 ; Profitlich et al, 2009 ; Prada et al, 2011 ; Kido et al, 2017 ; Liu et al, 2017 ; De Simone et al, 2018 ; Wen et al, 2020 ; Zhang et al, 2020 ). While mitral valve prolapse, mild mitral regurgitation, focal left ventricular uncompacting, atrial septal defect, ventricular septal defect, patent ductus arteriosus and pulmonary artery stenosis were also reported ( Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

Acute Lymphoblastic Leukemia in Combined Methylmalonic Acidemia and Homocysteinemia (cblC Type): A Case Report and Literature Review

et al. 2022

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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.

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Clinical characteristics and prognosis of children with methylmalonic acidemia

Yan

Zhang

Liu

et al. 2023

Preprint

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Background To analyze the clinical characteristics and prognosis of children with methylmalonic acidemia(MMA), and to improve clinicians' understanding of the disease. Methods A retrospective analysis was performed on the clinical data of children who were hospitalized and diagnosed with methylmalonic acidemia in the First Hospital of Jilin University from March 2015 to March 2021. Results Among the 42 children, 19 were male and 23 were female. The disease is more common in infancy. MMA is characterized by frequent vomiting, disturbance of consciousness, and metabolic acidosis, and the combined MMA The combined type is mostly growth retardation and nervous system damage. Conclusion Neurological damage is the most common in children with methylmalonic acidemia, and most children suffer from Growth retardation. Early diagnosis and treatment is the key to improve the quality of life of children.

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Methylmalonic Acidemia Complicated by Homocystinuria Diseases: a Report of Three Cases

Cited by 4 publications

References 17 publications

Different Pattern of Cardiovascular Impairment in Methylmalonic Acidaemia Subtypes

Different Pattern of Cardiovascular Impairment in Methylmalonic Acidaemia Subtypes

Acute Lymphoblastic Leukemia in Combined Methylmalonic Acidemia and Homocysteinemia (cblC Type): A Case Report and Literature Review

Clinical characteristics and prognosis of children with methylmalonic acidemia

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