• Journal of Genetic Medicine
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• 제11권1호
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• pp.22-26
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• 2014

Maple syrup urine disease (MSUD) is a disorder that involves the metabolism of branched chain amino acids, arising from a defect in branched-chain ${\alpha}$-keto acid dehydrogenase complex. Mutations have been identified in the BCKDHA, BCKDHB, or DBT genes, which encode different subunits of the BCKDH complex. Although encephalopathy and progressive neurodegeneration are its major manifestations, the severity of the disease may range from the severe classic type to milder intermediate variants. We report two Korean siblings with the milder intermediate MSUD who were diagnosed with MSUD by a combination of newborn screening tests using tandem mass spectrometry and family genetic screening for MSUD. At diagnosis, the patients' plasma levels were elevated for leucine, isoleucine, valine, and alloisoleucine, and branched-chain ${\alpha}$-keto acids and branched-chain ${\alpha}$-hydroxy acids were detected in their urine. BCKDHA, BCKDHB, and DBT analysis was performed, and two novel mutations were identified in BCKDHB. Our patients were thought to have the milder intermediate variant of MSUD, rather than the classic form. Although MSUD is a typical metabolic disease with poor prognosis, better outcomes can be expected if early diagnosis and prompt management are provided, particularly for milder forms of the disease.

• 대한유전성대사질환학회지
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• 제23권2호
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• pp.31-38
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• 2023

Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder caused by a deficiency in branched chain α-keto acid dehydrogenase (BCKAD). Between 1997, when Korea's MSUD case was first reported, and 2023, 14 cases were reported in the literature. 29% of the cases experienced developmental delay, and 29% expired. The prevalence of MSUD in Korea was estimated to be 1 in 230,000. Of 21 MSUD patients currently being treated at the Korea Genetics Research Center, 19 were detected through newborn screening program, and 2 were diagnosed by the symptoms. 14 MSUD patients had confirmed genetic mutations; 6 (43%) were BCKDHA and 8 (57%) were BCKDHB. In one case, a large deletion was observed. 4 patients had leucine levels above 2,000 (umo/L), and post-dialysis diet therapy was initiated in the newborn period. No patient required further dialysis as diet therapy and regular monitoring proved highly effective. Most MSUD patients were growing normally; weight and height growth were above the 50th percentile in 76% of the cases while BMI values were higher than normal in 71% of cases. Developmental delays were observed only in 2 cases (10%) and anticonvulsant use in 3 cases (14%). With newborn screening available to all Korean infants, early diagnosis and intervention should allow most patients to remain asymptomatic. However, ongoing surveillance, dietary management and continued patient compliance as well as rapid correction of acute metabolic decompensations remain critical to a favorable long-term prognosis.

• 대한유전성대사질환학회지
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• 제18권2호
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• pp.43-49
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• 2018

단풍시럽뇨병은 드문 상염색체 열성 대사 질환으로 측쇄 알파 케토산 탈수소효소 돌연변이에 의해 발생되는 질환이다. 측쇄 아미노산인 류신, 이소류신, 발린의 분해가 되지 않아 몸에 축적이 되고 식욕 저하, 구토, 기면, 이상행동, 발작 및 심한 경우 죽음을 초래한다. 세계적으로 단풍시럽뇨병의 유병율은 185,000명당 한명 이지만 한국에서는 극히 드물어 1,148,413명당 한명으로 보고된다. 이 증례의 여아는 만삭에 2.54 kg로 주산기 특이 병력 없이 출생한 첫째 아이로 특이 가족력 없었던 환아이다. 생후 10일경 식욕저하, 구토, 기면으로 타병원에서 대증치료 중에 선천성 대사이상 선별 검사 결과 상류신이 높아 전원 되었다. 환아는 기면, 혼수를 보였고 중추 수면무호흡으로 인공호흡기를 적용하였으며 소변에서 단풍시럽 냄새를 보였다. 뇌 초음파, 뇌 자기공명영상에서 뇌부종 소견을 보였으며 혈중아미노산 검사상 류신, 이소류신, 발린의 수치가 정상치보다 매우 높았다. 측쇄 아미노산 없는 특수분유를 시작했고 뇌부종으로 만니톨과 이뇨제를 사용했으며 고암모니아혈증으로 벤조산을 투약하였다. 경련 예방을 위해 페노바비탈을 투약하였으며 측쇄 알파 케토산 탈수소효소의 조효소인 타이아민 보충을 시작하였다. 치료함에 따라 혈중 측쇄 아미노산 수치가 감소하였고 뇌부종의 감소가 확인되었다. 29일 간의 신생아중환자실 처지 후 환아는 호흡 및 구강 식이 진행이 안정적이었고 병동으로 전동 후 퇴원하였다. 환아는 현재 5개월로 페노바비탈을 점차 줄여가고 있으며 측쇄 아미노산 수치도 안정적으로 유지되고 있다. 고개 가누기는 완벽하지 않지만 옹알이 및 뒤집기 가능하며 따라잡기 성장 및 발달을 보이고 있다. 유전학적 검사에서는 두 개의 BCKDHB 이형접합 돌연변이 p.Ala32Phefs*48와 p.Val130Phe를 확인 하였으며, 가족 검사를 통하여 부모 모두 보인자임을 확인하였다. 이 두 변이는 모두 이전에 한국에서 보고되지 않은 변이이다. 단풍시럽뇨병의 빠른 진단과 즉각적이고 적절한 치료가 환아의 생명을 유지하고 예후를 호전시킴을 본 증례를 통하여 다시 한 번 확인할 수 있다.

• Animal Bioscience
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• 제37권6호
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• pp.982-992
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• 2024

Objective: Jining Grey goat is a local Chinese goat breed that is well known for its high fertility and excellent meat quality but shows low meat production performance. Numerous studies have focused on revealing the genetic mechanism of its high fertility, but its highlighting meat quality and muscle growth mechanism still need to be studied. Methods: In this research, an integrative analysis of the genomics and transcriptomics of Jining Grey goats compared with Boer goats was performed to identify candidate genes and pathways related to the mechanisms of meat quality and muscle development. Results: Our results overlap among five genes (ABHD2, FN1, PGM2L1, PRKAG3, RAVER2) and detected a set of candidate genes associated with fatty acid metabolism (PRKAG3, HADHB, FASN, ACADM), amino acid metabolism (KMT2C, PLOD3, NSD2, SETDB1, STT3B, MAN1A2, BCKDHB, NAT8L, P4HA3) and muscle development (MSTN, PPARGC1A, ANKRD2). Several pathways have also been detected, such as the FoxO signaling pathway and Apelin signaling pathway that play roles in lipid metabolism, lysine degradation, N-glycan biosynthesis, valine, leucine and isoleucine degradation that involving with amino acid metabolism. Conclusion: The comparative genomic and transcriptomic analysis of Jining Grey goat and Boer goat revealed the mechanisms underlying the meat quality and meat productive performance of goats. These results provide valuable information for future breeding of goats.