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Lathosterolosis: A Relatively Mild Case with Cataracts and Learning Difficulties
Lathosterolosis is a rare defect of cholesterol synthesis. Only four previous cases have been reported, two of whom were siblings. We report a fifth patient, with a relatively mild phenotype. He presented at 5 years of age with bilateral posterior cataracts, which were managed with lensectomies and intraocular lens implants. He also had learning difficulties, with a full-scale IQ of 64 at 11 years of age. His head circumference is between the 0.4th and 2nd centiles, and he has mild hypotonia and subtle dysmorphism (a high-arched palate, anteverted nostrils, long philtrum and clinodactyly of toes). The diagnosis was established after sequencing a panel of genes associated with cataracts, which revealed compound heterozygous SC5D mutations: c.479C>G p.(Pro160Arg) and c.630C>A p.(Asp210Glu). The plasma lathosterol concentration was markedly raised at 219.8 μmol/L (control range 0.53–16.0), confirming the diagnosis. The c.630C>A p.(Asp210Glu) mutation has been reported in one previous patient, who also had a relatively mild phenotype (Ho et al., JIMD Rep 12:129–134, 2014). The mutation leads to a relatively conservative amino acid substitution, consistent with some residual enzyme activity. Our patient’s family did not notice any benefit from treatment with simvastatin. In summary, milder patients with lathosterolosis may present with learning difficulties, cataracts and very subtle dysmorphism. The diagnosis will be missed unless plasma sterols are analysed or relevant genes sequenced.
KeywordsCataracts Cholesterol synthesis Dysmorphism Lathosterolosis Learning difficulties SC5D mutations
Next-generation sequencing was supported by Fight for Sight UK (grant no. 1831). RLT is supported by a Medical Research Council/UK Research and Innovation Skills Development Fellowship (Ref: MR/R024952/1).
- Brunetti-Pierri N, Corso G, Rossi M et al (2002) Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of 3beta-hydroxysteroid-delta5-desaturase. Am J Hum Genet 71(4):952–958Google Scholar
- Gillespie RL, O’Sullivan J, Ashworth J et al (2014) Personalized diagnosis and management of congenital cataract by next-generation sequencing. Ophthalmology 121(11):2124–2137Google Scholar
- Gillespie RL, Urguhart J, Anderson B et al (2016) Next-generation sequencing in the diagnosis of metabolic disease marked by paediatric cataract. Ophthalmology 123(1):217–220Google Scholar
- Herman GE (2003) Disorder of cholesterol biosynthesis: prototypic metabolic malformation syndromes. Hum Mol Genet 12:R75–R88Google Scholar
- Ho ACC, Fung CW, Siu TS et al (2014) Lathosterolosis: a disorder of cholesterol biosynthesis resembling Smith-Lemli-Opitz syndrome. JIMD Rep 12:129–134Google Scholar
- Krakowiak PA, Wassif CA, Kratz L et al (2003) Lathosterolosis: an inborn error of human and murine cholesterol synthesis due to lathosterol 5-desaturase deficiency. Hum Mol Genet 12(13):1631–1641Google Scholar
- Merkens LS, Wassif C, Healy K et al (2009) Smith-Lemli-Opitz syndrome and inborn errors of cholesterol synthesis: summary of 2007 SLOS/RSH foundation scientific conference sponsored by National Institutes of Health. Genet Med 11(5):359–364Google Scholar
- Parnes S, Hunter AG, Jimenez C, Carpenter BF, MacDonald I (1990) Apparent Smith-Lemli-Opitz syndrome in a child with a previously undescribed form of mucolipidosis not involving the neurons. Am J Med Genet 35:397–405Google Scholar
- Rossi M, D’Armiento M, Parisi I et al (2007) Clinical phenotype of lathosterolosis. Am J Med Genet 143A(20):2371–2381Google Scholar
- Waterham HR (2006) Defects of cholesterol biosynthesis. FEBS Lett 580(23):5442–5449Google Scholar