BACKGROUND: Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is included in many newborn screening programmes worldwide. In addition to the prevalent mutation c.985A>G in the ACADM gene, potentially mild mutations like c.199T>C are frequently found in screening cohorts. There is ongoing discussion whether this mutation is associated with a clinical phenotype. METHODS: In 37 MCADD patients detected by newborn screening, biochemical phenotype (octanoylcarnitine (C8), ratios of C8 to acetylcarnitine (C2), decanoylcarnitine (C10) and dodecanoylcarnitine (C12) at screening and confirmation) and clinical phenotype (inpatient emergency treatment, metabolic decompensations, clinical assessments, psychometric tests) were assessed in relation to genotype. RESULTS: 16 patients were homozygous for c.985A>G (group 1), 11 compound heterozygous for c.199T>C and c.985A>G/another mutation (group 2) and 7 compound heterozygous for c.985A>G and mutations other than c.199T>C (group 3) and 3 carried neither c.985A>G nor c.199T>C but other known homozygous mutations (group 4). At screening C8/C2 and C8/C10, at confirmation C8/C2, C8/C10 and C8/C12 differed significantly between patients compound heterozygous for c.199T>C (group 2) and other genotypes. C8, C10 and C8/C2 at screening were strongly associated with time of sampling in groups 1 + 3 + 4, but not in group 2. Clinical phenotype did not differ between genotypes. Two patients compound heterozygous for c.199T>C and a severe mutation showed neonatal decompensation with hypoglycaemia. CONCLUSION: Biochemical phenotype differs between MCADD patients compound heterozygous for c.199T>C with a severe mutation and other genotypes. In patients detected by newborn screening, clinical phenotype does not differ between genotypes following uniform treatment recommendations. Neonatal decompensation can also occur in patients with the presumably mild mutation c.199T>C prior to diagnosis.
BACKGROUND: Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is included in many newborn screening programmes worldwide. In addition to the prevalent mutation c.985A>G in the ACADM gene, potentially mild mutations like c.199T>C are frequently found in screening cohorts. There is ongoing discussion whether this mutation is associated with a clinical phenotype. METHODS: In 37 MCADD patients detected by newborn screening, biochemical phenotype (octanoylcarnitine (C8), ratios of C8 to acetylcarnitine (C2), decanoylcarnitine (C10) and dodecanoylcarnitine (C12) at screening and confirmation) and clinical phenotype (inpatient emergency treatment, metabolic decompensations, clinical assessments, psychometric tests) were assessed in relation to genotype. RESULTS: 16 patients were homozygous for c.985A>G (group 1), 11 compound heterozygous for c.199T>C and c.985A>G/another mutation (group 2) and 7 compound heterozygous for c.985A>G and mutations other than c.199T>C (group 3) and 3 carried neither c.985A>G nor c.199T>C but other known homozygous mutations (group 4). At screening C8/C2 and C8/C10, at confirmation C8/C2, C8/C10 and C8/C12 differed significantly between patients compound heterozygous for c.199T>C (group 2) and other genotypes. C8, C10 and C8/C2 at screening were strongly associated with time of sampling in groups 1 + 3 + 4, but not in group 2. Clinical phenotype did not differ between genotypes. Two patients compound heterozygous for c.199T>C and a severe mutation showed neonatal decompensation with hypoglycaemia. CONCLUSION: Biochemical phenotype differs between MCADD patients compound heterozygous for c.199T>C with a severe mutation and other genotypes. In patients detected by newborn screening, clinical phenotype does not differ between genotypes following uniform treatment recommendations. Neonatal decompensation can also occur in patients with the presumably mild mutation c.199T>C prior to diagnosis.
Authors: Roman Yusupov; David N Finegold; Edwin W Naylor; Inderneel Sahai; Susan Waisbren; Harvey L Levy Journal: Mol Genet Metab Date: 2010-06-09 Impact factor: 4.797
Authors: Ho-Wen Hsu; Thomas H Zytkovicz; Anne Marie Comeau; Arnold W Strauss; Deborah Marsden; Vivian E Shih; George F Grady; Roger B Eaton Journal: Pediatrics Date: 2008-05 Impact factor: 7.124
Authors: N Gregersen; A I Blakemore; V Winter; B Andresen; S Kølvraa; L Bolund; D Curtis; P C Engel Journal: Clin Chim Acta Date: 1991-11-09 Impact factor: 3.786
Authors: Kristi Bentler; Shaohui Zhai; Sara A Elsbecker; Georgianne L Arnold; Barbara K Burton; Jerry Vockley; Cynthia A Cameron; Sally J Hiner; Mathew J Edick; Susan A Berry Journal: Mol Genet Metab Date: 2016-07-15 Impact factor: 4.797
Authors: A Maguolo; G Rodella; A Dianin; R Nurti; I Monge; E Rigotti; G Cantalupo; L Salviati; S Tucci; F Pellegrini; G Molinaro; F Lupi; P Tonin; A Pasini; N Campostrini; F Ion Popa; F Teofoli; M Vincenzi; M Camilot; G Piacentini; A Bordugo Journal: Mol Genet Metab Rep Date: 2020-08-05
Authors: Maria D Karaceper; Sara D Khangura; Kumanan Wilson; Doug Coyle; Marni Brownell; Christine Davies; Linda Dodds; Annette Feigenbaum; Deshayne B Fell; Scott D Grosse; Astrid Guttmann; Steven Hawken; Robin Z Hayeems; Jonathan B Kronick; Anne-Marie Laberge; Julian Little; Aizeddin Mhanni; John J Mitchell; Meranda Nakhla; Murray Potter; Chitra Prasad; Cheryl Rockman-Greenberg; Rebecca Sparkes; Sylvia Stockler; Keiko Ueda; Hilary Vallance; Brenda J Wilson; Pranesh Chakraborty; Beth K Potter Journal: Orphanet J Rare Dis Date: 2019-03-22 Impact factor: 4.123
Authors: Álvaro Martín-Rivada; Laura Palomino Pérez; Pedro Ruiz-Sala; Rosa Navarrete; Ana Cambra Conejero; Pilar Quijada Fraile; Ana Moráis López; Amaya Belanger-Quintana; Elena Martín-Hernández; Marcello Bellusci; Elvira Cañedo Villaroya; Silvia Chumillas Calzada; María Teresa García Silva; Ana Bergua Martínez; Sinziana Stanescu; Mercedes Martínez-Pardo Casanova; Miguel L F Ruano; Magdalena Ugarte; Belén Pérez; Consuelo Pedrón-Giner Journal: JIMD Rep Date: 2022-01-27