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Clinical and biochemical spectrum of D‐bifunctional protein deficiency
Author(s) -
Ferdinandusse Sacha,
Denis Simone,
Mooyer Petra A. W.,
Dekker Conny,
Duran Marinus,
SooraniLunsing Roelineke J.,
Boltshauser Eugen,
Macaya Alfons,
Gärtner Jutta,
Majoie Charles B. L. M.,
Barth Peter G.,
Wanders Ronald J. A.,
PollThe Bwee Tien
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20702
Subject(s) - cohort , bifunctional , hypotonia , pediatrics , life expectancy , medicine , phosphofructokinase 2 , peroxisomal disorder , peroxisome , biology , biochemistry , population , receptor , environmental health , enzyme , catalysis
Objective D‐bifunctional protein deficiency is an autosomal recessive inborn error of peroxisomal fatty acid oxidation. Although case reports and small series of patients have been published, these do not give a complete and balanced picture of the clinical and biochemical spectrum associated with this disorder. Methods To improve early recognition, diagnosis, prognosis, and management of this disorder and to provide markers for life expectancy, we performed extensive biochemical studies in a large cohort of D‐bifunctional protein–deficient patients and sent out questionnaires about clinical signs and symptoms to the responsible physicians. Results Virtually all children presented with neonatal hypotonia and seizures and died within the first 2 years of life without achieving any developmental milestones. However, within our cohort, 12 patients survived beyond the age of 2 years, and detailed information on 5 patients with prolonged survival (≥7.5 years) is provided. Interpretation Biochemical analyses showed that there is a clear correlation between several biochemical parameters and survival of the patient, with C26:0 β‐oxidation activity in cultured skin fibroblasts being the best predictive marker for life expectancy. Remarkably, three patients were identified without biochemical abnormalities in plasma, stressing that D‐bifunctional protein deficiency cannot be excluded when all peroxisomal parameters in plasma are normal. Ann Neurol 2006