Methylmalonic acidemia

Matsuda, Ichiro; Terashima, Takanori; Yamamoto, Jiro; Akaboshi, Izumi; Shinozuka, S.; Hattori, Shinzaburo; Nagata, Noriyuki; Oka, Yogo

doi:10.1007/bf00444303

Cited by 7 publications

(8 citation statements)

References 13 publications

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“…This report identifies the first reported case of MMA in Japan that survived long‐term. We previously reported long‐term outcomes in vitamin B12‐non‐responsive MMA patients were poor, and the expected survival rate to the age of 30 years was estimated at 45% …”

Section: Discussionmentioning

confidence: 75%

“…A 39‐year‐old female patient was diagnosed with vitamin B12‐non‐responsive MMA and followed in our institute . The patient was referred to our institute with symptoms of tachypnea, vomiting, lethargy, and poor appetite at 3 months of age.…”

Section: Case Reportmentioning

confidence: 99%

“…Almost 40 years ago, we reported the first vitamin B12non-responsive MMA patient in Japan. 2 She experienced three metabolic attacks during her childhood but no severe metabolic problems since her regular hemodialysis treatment (RHT) for chronic renal failure (CRF). However, she developed pulmonary artery hypertension (PAH) 18 years after receiving RHT.…”

Section: Introductionmentioning

confidence: 99%

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Pulmonary artery hypertension in methylmalonic acidemia

Kido

Mitsubuchi

Sakanashi

et al. 2016

Hemodialysis International

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Methylmalonic acidemia (MMA) is an autosomal recessive disorder that can be classified into two types: (1) vitamin B12-responsive and (2) vitamin B12-non-responsive. In MMA cases with long-term survival, renal failure is often a problem, and timing for kidney transplantation for MMA is controversial. We encountered a vitamin B12-non-responsive MMA case for which regular hemodialysis for renal failure was initiated; the patient was 16 years old when she first received regular hemodialysis and 35 years old when she developed pulmonary artery hypertension (PAH). PAH can complicate regular hemodialysis; however, PAH in this case was considered to be a complication of MMA because it was responsive to medical treatment and reversible. In this report, we discuss the role of regular hemodialysis in MMA and the causal relationship between MMA and regular hemodialysis for PAH.

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Section: Discussionmentioning

confidence: 75%

Section: Case Reportmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pulmonary artery hypertension in methylmalonic acidemia

Kido

Mitsubuchi

Sakanashi

et al. 2016

Hemodialysis International

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“…Lymphoblastoid cell lines were established by Epstein-Barr virus-mediated transformation of peripheral blood B lymphocytes from the patient (18). Studies were done on peripheral leukocytes taken from 10 ml of (heparinized) blood from the family members.…”

Section: Methodsmentioning

confidence: 99%

Maple syrup urine disease caused by a partial deletion in the inner E2 core domain of the branched chain alpha-keto acid dehydrogenase complex due to aberrant splicing. A single base deletion at a 5'-splice donor site of an intron of the E2 gene disrupts the consensus sequence in this region.

Mitsubuchi¹,

Nobukuni²,

Akaboshi³

et al. 1991

J. Clin. Invest.

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We have studied the molecular bases of maple syrup urine disease by analyzing the activity, subunit structure, mRNA sequence, and the genome of the affected enzyme. The branched chain a-keto acid dehydrogenase (BCKDH) activity in the patient was 4.2-4.5% of the control level. Immunoblot analysis revealed that the E2 subunit of BCKDH (M, 52,000) was absent and another protein band with an M, of 49,000 was present. We amplified the cDNA of the E2 subunit obtained from the patient's cell using the polymerase chain reaction method, then sequenced the amplified cDNA, in which a 78-bp deletion was identified. The consanguineous parents and a sister had two species of mRNA; the one corresponding to the normal E2 subunit and the other with a 78-bp deletion, whereas findings in a brother were normal. The molecular size of the translation products as deduced from the abnormal mRNA sequence was compatible with an abnormal protein band (M, 49,000) detected in the patient's cells by immunoblot analysis.Analysis of genomic DNA of BCKDH-E2 subunit revealed that the 78-bp deletion in the mRNA was caused by an exon skipping due to a single base deletion in the 5'-splice donor site. As a result ofthe mutation, part ofthe inner E2 core domain was omitted. The specified region of the inner E2 core domain was highly homologous to the region of the E2 subunit of pyruvate dehydrogenase and a-ketoglutalate dehydrogenase. These observations imply the biological importance of the region in the inner E2 core domain of BCKDH to maintain normal function of the activity.

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“…Although MSUD is one of the most common inborn errors of metabolism, first detected by Menkes et al (6), fundamental knowledge of the biochemical and genetic mechanisms involved in this disease is lacking. We established lymphoblastoid cell lines from patients with different types ofthis disease as these cells have advantages for studying biochemical genetics (20)(21)(22)(23)(24) Preparation ofthe BCKDH (El and EJ and PDH complexes from bovine tissue. The BCKDH (El and E2) complex was purified from bovine kidney, basically as described by Lawson et al (32).…”

Section: Introductionmentioning

confidence: 99%

Altered kinetic properties of the branched-chain alpha-keto acid dehydrogenase complex due to mutation of the beta-subunit of the branched-chain alpha-keto acid decarboxylase (E1) component in lymphoblastoid cells derived from patients with maple syrup urine disease.

Indo¹,

Kitano²,

Endo³

et al. 1987

J. Clin. Invest.

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Branched-chain ac-keto acid dehydrogense (BCKDH) complexes of lymphoblastoid cell lines derived from patients with classical maple syrup urine disease (MSUD) phenotypes were studied in terms of their catalytic functions and analyzed by immunoblotting, using affinity purified anti-bovine BCKDH antibody. Kinetic studies on three cell lines derived from patients with the classical phenotype showed sigmoidal or near sigmoidal kinetics for overall BCKDH activity and a deficiency of the El component activity.An immunoblot study revealed a markedly decreased amount of the E1, subunit accompanied by weak staining of the El. sublit.The E2 and E3 component exhibited a cross-reactive peptide. Thus, in at least some patients with MSUD, mutations of the E1f subunit might provide an explanation for the altered kinetic properties of the BCKDH complex.

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Methylmalonic acidemia

Cited by 7 publications

References 13 publications

Pulmonary artery hypertension in methylmalonic acidemia

Pulmonary artery hypertension in methylmalonic acidemia

Maple syrup urine disease caused by a partial deletion in the inner E2 core domain of the branched chain alpha-keto acid dehydrogenase complex due to aberrant splicing. A single base deletion at a 5'-splice donor site of an intron of the E2 gene disrupts the consensus sequence in this region.

Altered kinetic properties of the branched-chain alpha-keto acid dehydrogenase complex due to mutation of the beta-subunit of the branched-chain alpha-keto acid decarboxylase (E1) component in lymphoblastoid cells derived from patients with maple syrup urine disease.

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