Original article
The natural history of medium-chain acyl CoA dehydrogenase deficiency in the Netherlands: Clinical presentation and outcome

https://doi.org/10.1016/j.jpeds.2005.12.028Get rights and content

Objectives

To describe the clinical presentation and long-term follow-up of a large cohort of patients with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

Study design

A nationwide, retrospective analysis of clinical presentation and follow-up in 155 Dutch patients with MCAD deficiency.

Results

Most patients presented between 3 months and 5.1 years of age; 13% had symptoms as neonates not exclusively related to breast-feeding. An acute presentation before the diagnosis was made resulted in a mortality of 22% (25/114), whereas 21% (19/89) developed disabilities after the diagnosis. On follow-up, a total of 44 patients reported fatigue (35%; 28/80), muscle pain (31%; 25/80), and/or reduced exercise tolerance (39%; 31/80). Cardiac evaluation in 11 adult patients revealed no abnormalities in cardiac function explaining these complaints. Children with MCAD deficiency readily become overweight.

Conclusions

Mortality and morbidity were high in undiagnosed children with MCAD deficiency; establishment of the diagnosis significantly improves outcome. Strikingly, after the diagnosis and initiation of treatment, overweight and chronic complaints (fatigue, muscle pain, and reduced exercise tolerance) were prominent.

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

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