title: Clinical, genetic, and therapeutic diversity in 2 patients with severe mevalonate kinase deficiency.
abstract: Mevalonic aciduria (MA) represents the severest form of mevalonate kinase deficiency due to recessively inherited, loss-of-function MVK mutations. MA is an early-onset disorder characterized by a marked failure to thrive, diverse neurologic symptoms, dysmorphic features, and recurrent febrile episodes. However, significant clinical differences have been reported in the few cases published to date. Here we describe 2 unrelated Spanish patients with MA, emphasizing the clinical heterogeneity observed. One patient presented with the severe classic MA phenotype due to the homozygous p.Ile-268-Thr MVK genotype, with a poor response to conventional treatments. However, the anti-interleukin 1 agent anakinra in this patient resulted in improvement in many clinical and laboratory parameters. The second patient presented with an atypical milder phenotype because of an older age at disease onset, mild neurologic symptoms, absence of febrile episodes and dysmorphic features, and moderate-to-good response to conventional treatments. The novel p.Arg-241-Cys MVK mutation, associated with the already known p.Ser-135-Leu mutation, detected in this patient expands the genetic diversity of mevalonate kinase deficiency. This atypical presentation of MA suggests that it should be included in the differential diagnosis of unclassified patients with psychomotor retardation, failure to thrive or ataxia, even in the absence of febrile episodes.
authors.affiliation: Metabolic Diseases Unit, Pediatric Neurology Department, Hospital Universitario Son Dureta, Palma de Mallorca, Spain.
authors.forename: Angeles
authors.initials: A
authors.lastname: Ruiz Gomez
authors.forename: María Luz
authors.initials: ML
authors.lastname: Couce
authors.forename: Judit
authors.initials: J
authors.lastname: Garcia-Villoria
authors.forename: Angeles
authors.initials: A
authors.lastname: Torres
authors.forename: Ana
authors.initials: A
authors.lastname: Baña Souto
authors.forename: Jordi
authors.initials: J
authors.lastname: Yagüe
authors.forename: María Antonia
authors.initials: MA
authors.lastname: Vilaseca
authors.forename: Antonia
authors.initials: A
authors.lastname: Ribes
authors.forename: Juan I
authors.initials: JI
authors.lastname: Aróstegui
mesh_terms: D000483:Alleles; D001921:Brain / Q000473:pathology; D002524:Cerebellar Ataxia / Q000175:diagnosis / Q000235:genetics; D002531:Cerebellum / Q000473:pathology; D002648:Child; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005183:Failure to Thrive / Q000175:diagnosis / Q000235:genetics; D005335:Fever of Unknown Origin / Q000175:diagnosis / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007223:Infant; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D008297:Male; D054078:Mevalonate Kinase Deficiency / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D008798:Mevalonic Acid / Q000652:urine; D002527:Myoclonic Cerebellar Dyssynergia / Q000175:diagnosis / Q000235:genetics; D010641:Phenotype; D011596:Psychomotor Disorders / Q000175:diagnosis / Q000235:genetics
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D008798:Mevalonic Acid