Inborn defects of cholesterol biosynthesis are metabolic disorders presenting with multi-organ and tissues anomalies. Recently, a new autosomal recessive defect in four patients involving the demethylating enzyme C4-methylsterols (SC4MOL) has been described. In infancy, all showed microcephaly, congenital cataracts, growth delay, psoriasiform dermatitis, immune dysfunction and intellectual disability. Herein, we describe a new case of SC4MOL deficiency, showing bilateral congenital cataracts, psychomotor and development delay and learning disabilities in the early life. At 15 years, he showed small stature and behavioral disorder. His skin never demonstrated a marked psoriasiform rash, but only abundant dandruff of scalp. Despite numerous biochemical and genetic examinations, the diagnosis was missed until 19 years. Based on clinical evidences, such as congenital cataracts, microcephaly and developmental delay, a cholesterol biosynthesis defect was suspected. Blood C4-monomethyl- and C4-dimethylsterols levels were significantly higher than controls, suggesting a true deficiency of SC4MOL. SC4MOL gene sequencing showed mutations in both alleles (1st variant: c.731A>G, p.Y244C, already known; 2nd one: c.605G>A, p.G202E, new variant). Both mutations are absent in both EXAC database and healthy controls. His parents are found heterozygous. Finally, integrating clinical, metabolic, and genetic tests, we diagnosed the SC4MOL deficiency definitively. Notably, the interactions of multi-field skills are fruitful to diagnose a new defect of cholesterol biosynthesis. Therefore, we suggest that plasma sterol profile should be taken early into account for all undiagnosed patients showing clinical signs overlapping that of patient presented here.
|Titolo:||The sterol-C4-methyl oxidase deficiency in cholesterol biosynthesis and the juvenile psoriasis form dermatitis: A new case in a teenager Italian male|
|Data di pubblicazione:||2016|
|Appare nelle tipologie:||1.5 Abstract in rivista|