A male infant at your hospital has failed a hearing test and developed permanent hearing loss. His development was delayed as shown by an exaggerated Moro response (startle reflex) and his height was below the 3rd percentile. He was given supplemental vitamins, such as thiamine and riboflavin. At 5 months, he had motor weakness and hypotonia. At 10 months, he had feeding problems, recurrent emesis (vomiting), and metabolic acidosis from elevated lactate. <\/p>\n\n\n\n
Lab Findings<\/strong>1<\/sup><\/strong><\/p>\n\n\n\n Key Words:<\/strong> SUCLA2<\/em>, Anaplerotic Therapy, methylmalonic acid, succinylcarnitine<\/p>\n\n\n\n Analysis<\/strong> <\/p>\n\n\n\n Q1<\/strong>. Based on the Lactate and Pyruvate lab results, what type of dietary change would you recommend to help reduce the lactic acidosis in this patient?<\/p>\n\n\n\n Biochemistry1<\/sup>\u00a0<\/strong><\/p>\n\n\n\n Sanger sequencing revealed that the\u00a0patient has a compound heterozygous mutation\u00a0in SUCLA2<\/em>. Mutations in this gene lead to a\u00a0deficient succinyl-CoA synthetase, and therefore\u00a0the accumulation of succinyl-CoA, along with methylmalonic acid and succinylcarnitine, both\u00a0of which are succinyl-CoA\u2013related metabolites. SUCLA2 <\/em>is mostly expressed in the brain and\u00a0skeletal muscle.<\/p>\n\n\n\n Q2<\/strong>. After the dietary intervention, the patient\u2019s blood lactate returned to normal levels (1.8 mM). However, over time, the patient developed pronounced lethargy. Further analysis revealed elevated levels of methylmalonic acid and succinylcarnitine.1<\/sup> Propose an explanation for why energy levels might have decreased despite the initial benefit. <\/p>\n\n\n\n Q3.<\/strong> You were discussing this case with a colleague who informed you of a recent experimental trial to alleviate symptoms of another citric acid cycle disease. This trial aimed to help pediatric twin patients who experienced seizures and exhibited low motor development, truncal hypotonia, and cerebellar atrophy. After genetic sequencing, both children were diagnosed with aconitase 2 deficiency. They were prescribed triheptanoin. While taking triheptanoin, lab findings revealed increased urinary succinate, fumarate, and malate, and the patients\u2019 motor abilities improved. Alleviated symptoms were attributed to the metabolic conversion of triheptanoin to succinyl-CoA.2<\/sup> Explain how triheptanoin helped to alleviate the twins\u2019 symptoms. <\/p>\n\n\n\n Q4.<\/strong> Would you consider prescribing triheptanoin to your own patient?<\/p>\n\n\n\n References:<\/strong><\/p>\n\n\n\n Anny Vo, Celia Buetens, and John Jeong 4\/3\/2026 Case Study #7: Mitochondrial Citric Acid Cycle Disorder in Skeletal Muscles Case Background1 A male infant at your hospital has failed a hearing test and developed permanent hearing loss. His development was … Continue reading Test<\/th> Levels<\/th><\/tr><\/thead> Lactate\/Pyruvate Panel<\/td> Blood lactate: 8.6 mM (normal: 0.5-2.2 mM)Blood pyruvate: 0.14 mM (normal: 0.03-0.08)L\/P ratio: 61 <\/td><\/tr> Liquid Chromatography tandem Mass Spectrometry<\/td> Serum methylmalonic acid: 1,909 nM (normal: 73-271)<\/td><\/tr> Skeletal Muscle Acylcarnitine Analysis<\/td> Succinylcarnitine: 149 nmol\/g (normal < 9.4 nmol\/g) <\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n <\/p>\n\n\n\n
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