title: Perinatal onset mevalonate kinase deficiency.
abstract: Defects in mevalonate kinase, a critical rate-limiting enzyme in cholesterol and isoprene metabolism, have been associated with 2 clinical phenotypes: mevalonic aciduria, which presents in infancy or early childhood with growth failure, dysmorphic features, and neurologic disease; and hyperimmunoglobulinemia D and periodic fever syndrome, which usually presents outside the neonatal period as an autoinflammatory periodic fever syndrome. This report describes a kindred with 2 siblings affected by severe mevalonate kinase deficiency (mevalonic aciduria) with perinatal onset. Dysmorphic and central nervous system abnormalities, anemia, and cholestasis were prominent features in 1 sibling. Both cases were fatal, 1 in the immediate neonatal period and 1 in utero. The small number of cases of mevalonate kinase deficiency presenting in the perinatal period have typically been severely affected, with signs and symptoms of a severe multisystem disorder. Predominant features of perinatal onset mevalonate kinase deficiency include intrauterine growth restriction, cerebral ventriculomegaly, dysmorphic features, skeletal abnormalities, dyserythropoietic anemia with extramedullary erythropoiesis, thrombocytopenia, cholestatic liver disease, persistent diarrhea, renal failure, recurrent sepsis-like episodes, and failure to thrive. Clinical findings may mimic severe intrauterine viral infection, a chromosomal abnormality, or an acute sepsis syndrome, potentially contributing to delays in diagnosis of this rare condition. Perinatal onset mevalonate kinase deficiency is associated with a very poor prognosis, with death in utero or in early infancy. Detailed autopsy findings in mevalonate kinase deficiency have rarely been reported.
authors.affiliation: Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Steiner
authors.forename: Richard A
authors.initials: RA
authors.lastname: Ehrenkranz
authors.forename: Steven M
authors.initials: SM
authors.lastname: Peterec
authors.forename: Robert D
authors.initials: RD
authors.lastname: Steiner
authors.forename: Miguel
authors.initials: M
authors.lastname: Reyes-Múgica
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Gallagher
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D008297:Male; D054078:Mevalonate Kinase Deficiency / Q000235:genetics* / Q000473:pathology*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011247:Pregnancy