Lathosterolosis - A Rare Treatable Cause for Global Developmental Delay, Cataract, and Liver Dysfunction Masquerading as Galactosemia

Excerpt

To the Editor: Lathosterolosis (OMIM#607330) is an autosomal recessive disorder of cholesterol biosynthesis. The first case was published in 2002 [1]. A 5.5-y-old girl born to consanguineous marriage presented with developmental delay and seizures (focal and generalized) from one month of age. The child was operated on for bilateral cataract. She attained walking with support and spoke 20 meaningful words. On examination, the occipitofrontal circumference (44 cm), weight (12.8 kg), and length (85 cm) all were less than the WHO -3 Z score. Flat bitemporal narrowing, nasal bridge, right eye exotropia, triangular face, normal vision, hearing, and hypotonia were noted. The complete hemogram was normal. The aspartate aminotransferase- 57.8 U/L (<32), and alanine aminotransferase- 77.5 U/L (<33) were increased with normal alkaline phosphatase (35 U/L) and gamma-glutamyl transferase (26 U/L). Ultrasound showed altered echotexture of the liver. MRI brain showed mild cortical atrophy and electroencephalogram showed multifocal epilepsy. The Erythrocyte GALT assay was normal, and IgG titers for rubella and cytomegalovirus (CMV) were negative. Whole exome sequencing showed a novel likely pathogenic missense change in SC5D NM_006918.5: c.13C>T: p.Leu5Phe and segregates with the condition in the family. The plasma sterol levels revealed high lathosterol- 54 μmol/L (normally <10), with normal 7-dehydrocholesterol, and total cholesterol suggestive of Lathosterolosis. The child was treated with simvastatin, 5 mg initially and the dose was increased to 10 mg daily over 6 wk later. Her lathosterol decreased to 15 μmol/L. …