Clinical, genetic, and therapeutic diversity in 2 patients with severe mevalonate kinase deficiency

• Published in: Pediatrics (Evanston) 2012-02, Vol.129 (2), p.e535-e539
• Main Authors: Ruiz Gomez, Angeles, Couce, María Luz, Garcia-Villoria, Judit, Torres, Angeles, Baña Souto, Ana, Yagüe, Jordi, Vilaseca, María Antonia, Ribes, Antonia, Aróstegui, Juan I
• Format: Article
• Language: English
• Subjects: Alleles; Brain - pathology; Causes of; Cerebellar Ataxia - diagnosis; Cerebellar Ataxia - genetics; Cerebellum - pathology; Child; Diagnosis, Differential; DNA Mutational Analysis; Failure to Thrive - diagnosis; Failure to Thrive - genetics; Fever of Unknown Origin - diagnosis; Fever of Unknown Origin - genetics; Gene mutation; Gene mutations; Genes, Recessive - genetics; Genetic aspects; Genetic Variation; Genetics; Genotype; Genotype & phenotype; Health aspects; Humans; Infant; Interleukin 1 Receptor Antagonist Protein - therapeutic use; Magnetic Resonance Imaging; Male; Medical treatment; Metabolic diseases; Metabolic disorders; Mevalonate; Mevalonate Kinase Deficiency - diagnosis; Mevalonate Kinase Deficiency - drug therapy; Mevalonate Kinase Deficiency - genetics; Mevalonic Acid - urine; Mutation; Myoclonic Cerebellar Dyssynergia - diagnosis; Myoclonic Cerebellar Dyssynergia - genetics; Pediatrics; Phenotype; Psychomotor Disorders - diagnosis; Psychomotor Disorders - genetics
• ISSN: 0031-4005; 1098-4275
• DOI: 10.1542/peds.2010-2192

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.