Original articleThe natural history of medium-chain acyl CoA dehydrogenase deficiency in the Netherlands: Clinical presentation and outcome
Section snippets
Methods
The Medical Ethical Committee of the University Medical Center Groningen (MEC 98/04/075) approved the study protocol. In The Netherlands, medical care for patients with a metabolic disorder is restricted to the metabolic divisions of pediatric departments in the 8 university hospitals. To perform a national analysis of MCAD-deficient patients, we contacted all of these divisions and their affiliated metabolic laboratories, all of which provided information on their patients with known MCAD
Genotype in Dutch Families With MCAD Deficiency
Genetic analysis of the ACADM gene (MIM 607008) performed in 99 of 110 Dutch families with MCAD deficiency revealed 8 different mutations, of which the c.985A>G mutations is by far the most common, followed by the c.233T>C mutation (Table I). Subjects of 4 families were analyzed only for the presence of the c.985A>G mutation and found to be heterozygous. In 1 family, sequencing of the entire ACADM gene revealed only 1 heterozygous c.233T>C mutation, although the subjects clearly demonstrated
Discussion
Mortality and morbidity in 155 patients with MCAD deficiency in The Netherlands were similar to findings in previous reports of patients with MCAD deficiency.3, 4, 5, 6, 7, 8 However, the present study addresses important issues regarding clinical presentation and follow-up in MCAD-deficient patients, with implications for neonatal screening.
This study reports on all known genotypes in Dutch patients with clinical symptoms related to MCAD deficiency. The c.985A>G mutation was by far the most
References (37)
- et al.
Suberylglycine excretion in the urine from a patient with dicarboxylic aciduria
Clin Chim Acta
(1976) - et al.
Medium-chain acyl-coenzyme A dehydrogenase deficiencyclinical course in 120 affected children
J Pediatr
(1994) - et al.
A fatal neonatal case of medium-chain acyl-coenzyme A dehydrogenase deficiency with homozygous A→G-985 transition
J Pediatr
(1992) - et al.
Neonatal onset of medium-chain acyl-coenzyme A dehydrogenase deficiency with confusing biochemical features
J Pediatr
(1995) - et al.
Medium-chain acyl-CoA dehydrogenase deficiencysudden and unexpected death of a 45-year-old woman
Genet Med
(1999) - et al.
ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography: summary article. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography)
J Am Coll Cardiol
(2003) - et al.
Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptomsidentification and characterization of a new, prevalent mutation that results in mild MCAD deficiency
Am J Hum Genet
(2001) - et al.
The tissue-specific expression and developmental regulation of two nuclear genes encoding rat mitochondrial proteinsmedium-chain acyl-CoA dehydrogenase and mitochondrial malate dehydrogenase
J Biol Chem
(1989) - et al.
Mice heterozygous for a defect in mitochondrial trifunctional protein develop hepatic steatosis and insulin resistance
Gastroenterology
(2005) - et al.
Mitochondrial fatty acid oxidation disorders
The inborn errors of mitochondrial fatty acid oxidation
J Inherit Metab Dis
Medium-chain acyl-CoA dehydrogenase deficiency
Arch Dis Child
Morbidity and mortality in medium-chain acyl coenzyme A dehydrogenase deficiency
Arch Dis Child
Prospective surveillance study of medium-chain acyl-CoA dehydrogenase deficiency in the UK
Arch Dis Child
Outcome of medium-chain acyl-CoA dehydrogenase deficiency after diagnosis
Arch Dis Child
Neonatal symptoms in medium-chain acyl coenzyme A dehydrogenase deficiency
Arch Dis Child
A novel mutation in medium-chain acyl-CoA dehydrogenase causes sudden neonatal death
J Clin Invest
Pulmonary haemorrhage and cardiac dysfunction in a neonate with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
Acta Paediatr
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