Clinical phenotype of lathosterolosis.
Lathosterolosis (LS) is a defect of cholesterol biosynthesis due to the deficiency of the enzyme sterol-C5-desaturase. Only two patients have been described to date, both presenting with multiple malformations, mental retardation, and liver involvement. In addition in one of them pathological examination revealed mucolipidosis-like inclusions on optic microscopy analysis, and peculiar lysosomal lamellar bodies on electron microscopy analysis. This study is focused on a better characterization of the clinical phenotype of LS. We describe a further case in a fetus, sibling of the first patient reported, presenting with neural tube defect, craniofacial and limb anomalies, and prenatal liver involvement. The fetal phenotype suggests the possible occurrence of significant intrafamilial variability in LS, and expands the phenotypic spectrum of the disease. Histological examination of autopsy samples from the fetus and skin fibroblasts from the living sibling suggested that the mucolipidosis-like picture previously reported is not a constant feature of LS, being possibly associated with the most severe biochemical defects, but confirmed the ultrastructural finding of lamellar inclusions. The LS phenotype appears to be characterized by the distinctive association of a recognizable pattern of congenital anomalies, involving axial and appendicular skeleton, liver, central nervous and urogenital systems, and lysosomal storage. This condition partially overlaps with other defects of sterol metabolism, suggesting intriguing pathogenic links among these conditions.
Rossi
Massimiliano
M
Dipartimento di Pediatria, Federico II University, Naples, Italy, and Department of Radiology, Great Ormond Street Hospital for Children, London, UK.
D'Armiento
Maria
M
Parisi
Ida
I
Ferrari
Paola
P
Hall
Christine M
CM
Cervasio
Mariarosaria
M
Rivasi
Francesco
F
Balli
Fiorella
F
Vecchione
Raffaella
R
Corso
Gaetano
G
Andria
Generoso
G
Parenti
Giancarlo
G
D002648:Child; D002675:Child, Preschool; D002784:Cholesterol / Q000378:metabolism*; D000013:Congenital Abnormalities / Q000473:pathology; D005260:Female; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000201:enzymology / Q000473:pathology*; D008297:Male; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency / Q000378:metabolism; D010641:Phenotype; D019082:Smith-Lemli-Opitz Syndrome / Q000235:genetics / Q000473:pathology
C033144:lathosterol delta-5-dehydrogenase; C001521:lathosterol; D002784:Cholesterol; D044925:Oxidoreductases Acting on CH-CH Group Donors