MSMO1 deficiency: a potentially partially treatable, ultrarare neurodevelopmental disorder with psoriasiform dermatitis, alopecia and polydactyly

Abstract

MSMO1 deficiency (OMIM #616834) is an ultrarare autosomal recessive disorder of distal cholesterol metabolism with only five cases reported to date. The disorder is caused by missense variants in the MSMO1 gene encoding methylsterol monooxygenase 1, leading to the accumulation of methylsterols. Clinically, MSMO1 deficiency is characterized by growth and developmental delay, often in association with congenital cataracts, microcephaly, psoriasiform dermatitis and immune dysfunction. Treatment with oral and topical cholesterol supplements and statins was reported to improve the biochemical, immunological, and cutaneous findings, supporting a potential treatment following the precision diagnosis of MSMO1 deficiency. We describe two siblings from a consanguineous family presenting with novel clinical features of polydactyly, alopecia and spasticity. Whole-exome sequencing revealed a novel, homozygous c.548A > C, p.(Glu183Ala) variant. Based on previously published treatment algorithms, we initiated a modified dosage regime with systemic cholesterol supplementation, statins and bile acid along with topical application of a cholesterol/statin formulation. This resulted in a marked improvement of psoriasiform dermatitis and some hair growth.

A founder COL4A3 pathogenic variant resulting in Alport syndrome and thin basement membrane disease: a case report series

“…A recent demonstration of a founder effect was described in an isolated Czech Romani population, where two variants in the COL4A4 and COL4A3 genes contributed to a high prevalence of kidney failure (21). Currently, there is almost no literature describing genetic diseases from the Marneuli region of South Georgia, except for a single case report involving siblings with ultra-rare SC4MOL deficiency and a novel mutation in the MSMO1 gene (22).…”