3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: Clinical presentation and outcome in a series of 37 patients.
Date
2017Author
Schmitt, Robert Niklas
Roland, Dominique
Rutsch, Frank
Santer, Rene
Schlune, Andrea
Staufner, Christian
Schwab, Karl Otfried
Mitchell, Grant A.
Sass, Joern Oliver
Balci, Mehmet Cihan
Goekcay, Gülden Fatma
Gruenert, Sarah Catharina
Schlatter, Sonja Marina
Gemperle-Britschgi, Corinne
Mrazova, Lenka
Bischof, Felix
ÇOKER, MAHMUT
Das, Anibh M.
Demirkol, Muebeccel
de Vries, Maaike
Haeberle, Johannes
Ucar, Sema Kalkan
Lotz-Havla, Amelie Sophia
Luecke, Thomas
Metadata
Show full item recordAbstract
3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is a rare inborn error of ketone body synthesis and leucine degradation, caused by mutations in the HMGCL gene. In order to obtain a comprehensive view on this disease, we have collected clinical and biochemical data as well as information on HMGCL mutations of 37 patients (35 families) from metabolic centers in Belgium, Germany, The Netherlands, Switzerland, and Turkey. All patients were symptomatic at some stage with 94% presenting with an acute metabolic decompensation. In 50% of the patients, the disorder manifested neonatally, mostly within the first days of life. Only 8% of patients presented after one year of age. Six patients died prior to data collection. Long-term neurological complications were common. Half of the patients had a normal cognitive development while the remainder showed psychomotor deficits. We identified seven novel HMGCL mutations. In agreement with previous reports, no clear genotype phenotype correlation could be found. This is the largest cohort of HMGCLD patients reported so far, demonstrating that HMGCLD is a potentially life-threatening disease with variable clinical outcome. Our findings suggest that the clinical course of HMGCLD cannot be predicted accurately from HMGCL genotype. The overall outcome in HMGCLD appears limited, thus rendering early diagnosis and strict avoidance of metabolic crises important. (C) 2017 Elsevier Inc. All rights reserved.
Collections
- Makale [92796]