Carnitine transporter and holocarboxylase synthetase deficiencies in The Faroe Islands

• Published in: Journal of inherited metabolic disease 2007-06, Vol.30 (3), p.341-349
• Main Authors: Lund, A. M, Joensen, F, Hougaard, D. M, Jensen, L. K, Christensen, E, Christensen, M, Nørgaard-Petersen, B, Schwartz, M, Skovby, F
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Carnitine - blood; Carnitine - therapeutic use; Errors of metabolism; Feasibility Studies; Female; Follow-Up Studies; Gene Frequency; Genetic Carrier Screening; Genetic Testing; Geography; Holocarboxylase Synthetase Deficiency - diagnosis; Holocarboxylase Synthetase Deficiency - drug therapy; Holocarboxylase Synthetase Deficiency - epidemiology; Holocarboxylase Synthetase Deficiency - genetics; Humans; Infant; Infant, Newborn; Lipids (lysosomal enzyme disorders, storage diseases); Male; Medical genetics; Medical sciences; Metabolic diseases; Molecular Sequence Data; Neonatal Screening - methods; Norway - epidemiology; Organic Cation Transport Proteins - deficiency; Organic Cation Transport Proteins - genetics; Solute Carrier Family 22 Member 5; Tandem Mass Spectrometry
• ISSN: 0141-8955; 1573-2665
• DOI: 10.1007/s10545-007-0527-9

Carnitine transporter deficiency (CTD) and holocarboxylase synthetase deficiency (HLCSD) are frequent in The Faroe Islands compared to other areas, and treatment is available for both disorders. In order to evaluate the feasibility of neonatal screening in The Faroe Islands we studied detection in the neonatal period by tandem mass spectrometry, carrier frequencies, clinical manifestations, and effect of treatment of CTD and HLCSD. We found 11 patients with CTD from five families and 8 patients with HLCSD from five families. The natural history of both disorders varied extensively among patients, ranging from patients who presumably had died from their disease to asymptomatic individuals. All symptomatic patients responded favourably to supplementation with l-carnitine (in case of CTD) or biotin (in case of HLCSD), but only if treated early. Estimates of carrier frequency of about 1:20 for both disorders indicate that some enzyme-deficient individuals remain undiagnosed. Prospective and retrospective tandem mass spectrometry (MS/MS) analyses of carnitines from neonatally obtained filter-paper dried blood-spot samples (DBSS) uncovered 8 of 10 individuals with CTD when using both C₀ and C₂ as markers (current algorithm) and 10 of 10 when using only C₀ as marker. MS/MS analysis uncovered 5 of 6 patient with HLCSD. This is the first study to report successful neonatal MS/MS analysis for the diagnosis of HLCSD. We conclude that CTD and HLCSD are relatively frequent in The Faroe Islands and are associated with variable clinical manifestations, and that diagnosis by neonatal screening followed by early therapy will secure a good outcome.