P091: Managing BCKDK deficiency on the frontier: Treating BCKDK deficiency in an underserved Hutterite community

Discussion: The patient had elevated plasma sterol levels and methylsterol/sterol ratio as well as normal cholesterol, consistent with prior patients with SC4MOL deficiency.In addition to global developmental delay and congenital cataracts, she exhibited more CNS involvement, but very mild skin pathology compared to previous reports.Conclusion: SC4MOL deficiency is an ultra-rare disorder of cholesterol biosynthesis amenable to treatment with HMG-coA reductase inhibitor and oral cholesterol supplementation.Additional reports, case series, and clinical trials are needed to better understand the phenotypic spectrum and develop consensus regarding optimal therapeutic treatment and biochemical monitoring targets.Introduction: Deficiency in sterol C4 methyl oxidase, encoded by SC4MOL (previously MSMOL1), is the first autosomal recessive disorder identified in the sterol demethylation complex.This complex includes 3 beta-hydroxysteroid C4-methyl oxidase (4-alpha-methylsterol oxidase) which converts dihydro-TMAS to cholestra-8(9)-en-3beta-ol in the cholesterol synthesis pathway.SC4MOL deficiency has been most consistently characterized by developmental delay, intellectual disability, congenital cataracts, and eczema to psoriasiform dermatitis.Other features include microcephaly, growth delay, and structural brain abnormalities.Ten patients from seven different families have been described in the literature since 2011.Case Presentation: The patient is a 5-year-old female with history of congenital cataracts (s/p removal), sensitive skin/eczema, spasticity of lower extremities, and non-specific white matter changes on brain MRI who was born AGA at term to nonconsanguineous parents after an uncomplicated pregnancy.Gross motor and speech delays were noted at the age of 6 months which prompted further evaluation by genetics.Diagnostic Workup: CMA and trio genome at age 1 year were non-diagnostic.Trio genome reanalysis at age 4 showed two variants of uncertain significance in MSMO1 not previously reported: c.405G>T (p.Trp135Cys) and c.801_804delinsATGA (p.Trp267Ter).Initial quantitative plasma sterol analysis showed elevation of 4 alpha-methyl-and 4, 4'-dimethylsterols with elevated methylsterol/cholesterol % ratio of 0.7 (ref <0.1).Clinical, genetic, and biochemical evidence was consistent with SC4MOL deficiency due to biallelic variants in MSMO1.