Vitamin B12-unresponsive methylmalonic acidemia type mut-

2020 ◽  
Author(s):  
Keyword(s):  
Vitamin B12 ◽  
Methylmalonic Acidemia

scholarly journals 858 ORAL TREATMENT OF INHERITED VITAMIN B12-RESPONSIVE METHYLMALONIC ACIDEMIA (MMA)

1985 ◽  
Vol 19 (4) ◽  
pp. 253A-253A
Author(s):  
Flemming Skovby ◽  
John Harper ◽  
Maurice J Mahoney
Keyword(s):  
Vitamin B12 ◽  
Oral Treatment ◽  
Methylmalonic Acidemia

scholarly journals The vitamin B12 processing enzyme, mmachc, is essential for zebrafish survival, growth and retinal morphology

2020 ◽  
Vol 29 (13) ◽  
pp. 2109-2123 ◽  
Author(s):  
Jennifer L Sloan ◽  
Nathan P Achilly ◽  
Madeline L Arnold ◽  
Jerrel L Catlett ◽  
Trevor Blake ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Cholesterol Metabolism ◽  
Wide Spectrum ◽  
Clinical Manifestations ◽  
Methylmalonic Acidemia ◽  
Fluorescent Reporters ◽  
Early Embryonic Lethality ◽  
Full Complement ◽  
Human Disorder ◽  
Cobalamin Metabolism

Abstract Cobalamin C (cblC) deficiency, the most common inborn error of intracellular cobalamin metabolism, is caused by mutations in MMACHC, a gene responsible for the processing and intracellular trafficking of vitamin B12. This recessive disorder is characterized by a failure to metabolize cobalamin into adenosyl- and methylcobalamin, which results in the biochemical perturbations of methylmalonic acidemia, hyperhomocysteinemia and hypomethioninemia caused by the impaired activity of the downstream enzymes, methylmalonyl-CoA mutase and methionine synthase. Cobalamin C deficiency can be accompanied by a wide spectrum of clinical manifestations, including progressive blindness, and, in mice, manifests with very early embryonic lethality. Because zebrafish harbor a full complement of cobalamin metabolic enzymes, we used genome editing to study the loss of mmachc function and to develop the first viable animal model of cblC deficiency. mmachc mutants survived the embryonic period but perished in early juvenile life. The mutants displayed the metabolic and clinical features of cblC deficiency including methylmalonic acidemia, severe growth retardation and lethality. Morphologic and metabolic parameters improved when the mutants were raised in water supplemented with small molecules used to treat patients, including hydroxocobalamin, methylcobalamin, methionine and betaine. Furthermore, mmachc mutants bred to express rod and/or cone fluorescent reporters, manifested a retinopathy and thin optic nerves (ON). Expression analysis using whole eye mRNA revealed the dysregulation of genes involved in phototransduction and cholesterol metabolism. Zebrafish with mmachc deficiency recapitulate the several of the phenotypic and biochemical features of the human disorder, including ocular pathology, and show a response to established treatments.

scholarly journals Identification of a novel deletion in the MMAA gene in two Iranian siblings with vitamin B12-responsive methylmalonic acidemia

2016 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatemeh Keyfi ◽  
Mohammad Reza Abbaszadegan ◽  
Arndt Rolfs ◽  
Slobodanka Orolicki ◽  
Morteza Moghaddassian ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Methylmalonic Acidemia

Dietary therapy in two patients with vitamin B12-unresponsive methylmalonic acidemia

1981 ◽  
Vol 135 (3) ◽  
pp. 305-312 ◽  
Author(s):  
T. Satoh ◽  
K. Narisawa ◽  
Y. Igarashi ◽  
T. Saitoh ◽  
K. Hayasaka ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Methylmalonic Acidemia ◽  
Dietary Therapy

scholarly journals A rare mutation c.1663G>A (p.A555T) in the MMUT gene associated with mild clinical and biochemical phenotypes of methylmalonic acidemia in 30 Chinese patients

2020 ◽  
Author(s):  
Lili Liang ◽  
Ruixue Shuai ◽  
Yue Yu ◽  
Wenjuan Qiu ◽  
Linghua Shen ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Vitamin B12 ◽  
Disease Onset ◽  
Methylmalonic Acidemia ◽  
Chinese Patients ◽  
Causative Gene ◽  
Rare Type ◽  
Rare Mutation ◽  
Wide Range ◽  
Before And After

Abstract Background Methylmalonic acidemia is an inherited organic acid metabolic disease. it involves multiple physiological systems and has variable manifestations. The primary causative gene MMUT carries wide range of mutations, and one of them, c.1663G > A (p.A555T), is considered to be of an extremely rare type. So far, little is known about the clinical features of patients carrying this mutation. In the present study, we aimed to define the clinical and biochemical features of the patients with this genotype.Methods Among 328 mut type methylmalonic acidemia patients from multiple hospitals in China, we collected 30 patients sharing the mutation c.1663G > A (p.A555T) in the MMUT gene. Their clinical characteristics and biochemical index were described in detail and compared with methylmalonic acidemia patients without this variant.Results Most of these patients were diagnosed via newborn screening (26/30), treated in a timely manner, and kept healthy (24/30). Disease onset occurred in 7 patients. Mental retardation occurred in 4 patients. Vitamin B12 is responsive in 100% of these patients (29/29). The blood propionylcarnitine, blood propionylcarnitine/acetylcarnitine ratio, urinary methylmalonic acid, urinary methylcitric acid before and after treatment in c.1663G > A (p.A555T) carrying patients were much lower than those in non-c.1663G > A (p.A555T) carrying patients.Conclusion Compared to patients with other mutations in the MMUT gene, patients with the c.1663G > A (p.A555T) mutation showed later onset, milder clinical phenotype, lighter biochemical abnormalities, better vitamin B12 responsiveness, lower morbidity, easier metabolic control, and thereby better prognosis. Newborn screening project plays an important role in early diagnosis, treatment, and prognosis of these patients.

scholarly journals Proteinuria as a presenting sign of combined methylmalonic acidemia and homocysteinemia: case report

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ru-Yue Chen ◽  
Xiao-Zhong Li ◽  
Qiang Lin ◽  
Yun Zhu ◽  
Yun-Yan Shen ◽  
...  
Keyword(s):  
Organic Acids ◽  
Vitamin B12 ◽  
Metabolic Diseases ◽  
Methylmalonic Acid ◽  
Clinical Manifestations ◽  
Methylmalonic Aciduria ◽  
Methylmalonic Acidemia ◽  
Initial Presentation ◽  
Gas Chromatography Mass Spectrometry ◽  
Persistent Proteinuria

Abstract Background Disorders of the metabolism and absorption of vitamin B12 can lead to decrease in activity of methionine synthetase and methylmalonate coenzyme A mutase (MMUT), which results in increased levels of methylmalonic acid and homocysteine in blood and urine. Often, combined methylmalonic acidemia (MMA) and homocysteinemia is misdiagnosed due to a lack of specific symptoms. The clinical manifestations are diverse, but proteinuria as the initial presentation is rare. Case presentation Two cases of MMA with homocysteinemia in children are reported. Proteinuria were a primary presenting symptom, followed by anemia and neurologic symptoms (frequent convulsions and unstable walking, respectively). Screening of amino acids and acyl carnitine in serum showed that the propionyl carnitine:acetylcarnitine ratio increased. Profiling of urinary organic acids by gas chromatography–mass spectrometry revealed high levels of methylmalonic acid. Homocysteine content in blood was increased. Comprehensive genetic analyses of peripheral blood-derived DNA demonstrated heterozygous variants of methylmalonic aciduria type C and homocystinuria (MMACHC) and amnionless (AMN) genes in our two patients, respectively. After active treatment, the clinical manifestations in Case 1 were relieved and urinary protein ceased to be observed; Case 2 had persistent proteinuria and was lost to follow-up. Conclusions Analyses of the organic acids in blood and urine suggested MMA combined with homocysteinemia. In such diseases, reports of renal damage are uncommon and proteinuria as the initial presentation is rare. Molecular analysis indicated two different genetic causes. Although the pathologic mechanisms were related to vitamin B12, the severity and prognosis of renal lesions were different. Therefore, gene detection provides new insights into inherited metabolic diseases.

scholarly journals A rare mutation c.1663G>A (p.A555T) in the MMUT gene associated with mild clinical and biochemical phenotypes of methylmalonic acidemia in 30 Chinese patients

2020 ◽  
Author(s):  
Lili Liang ◽  
Ruixue Shuai ◽  
Yue Yu ◽  
Wenjuan Qiu ◽  
Linghua Shen ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Vitamin B12 ◽  
Disease Onset ◽  
Methylmalonic Acidemia ◽  
Chinese Patients ◽  
Compound Heterozygous ◽  
Causative Gene ◽  
Rare Type ◽  
Wide Range ◽  
Before And After

Abstract Background: Methylmalonic acidemia is an inherited organic acid metabolic disease. it involves multiple physiological systems and has variable manifestations. The primary causative gene MMUT carries wide range of mutations, and one of them, c.1663G>A (p.A555T), is considered to be of an extremely rare type. So far, little is known about the clinical features of patients carrying this mutation. In the present study, we aimed to define the clinical and biochemical features of the patients with this genotype.Methods: Among 328 mut type methylmalonic acidemia patients from multiple hospitals in China, we collected 30 compound heterozygous patients sharing the mutation c.1663G>A (p.A555T) in the MMUT gene. Their clinical characteristics and biochemical index were described in detail and compared with methylmalonic acidemia patients without this variant. Results: Most of these patients were diagnosed via newborn screening (26/30), treated in a timely manner, and kept healthy (24/30). Disease onset occurred in 7 patients. Developmental delay or intellectual impairment occurred in 4 patients. Vitamin B12 is responsive in 100% of these patients (29/29). The blood propionylcarnitine, blood propionylcarnitine/acetylcarnitine ratio, urinary methylmalonic acid, urinary methylcitric acid before and after treatment in c.1663G>A (p.A555T) carrying patients were much lower than those in non-c.1663G>A (p.A555T) carrying patients.Conclusion: Compared to patients with other mutations in the MMUT gene, patients with the c.1663G>A (p.A555T) mutation showed later onset, milder clinical phenotype, lighter biochemical abnormalities, better vitamin B12 responsiveness, lower morbidity, easier metabolic control, and thereby better prognosis. Newborn screening project plays an important role in early diagnosis, treatment, and prognosis of these patients.

Prenatal treatment of a patient with vitamin B12-responsive methylmalonic acidemia

1990 ◽  
Vol 117 (6) ◽  
pp. 923-926 ◽  
Author(s):  
S.B. van der Meer ◽  
L.J.M. Spaapen ◽  
B. Fowler ◽  
C. Jakobs ◽  
W.J. Kleijer ◽  
...  
Keyword(s):  
Vitamin B12 ◽  
Methylmalonic Acidemia ◽  
Prenatal Treatment
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