Apparent Smith–Lemli–Opitz syndrome in a child with a previously undescribed form of mucolipidosis not involving the neurons

Abstract

A diagnosis of Smith-Lemli-Opitz syndrome was made shortly after birth in a small-for-dates infant, on the basis of a characteristic face, penoscrotal hypospadias, bilateral postaxial hexadactyly, and bilateral syndactyly of toes 2-3. The clinical course was marked by failure to thrive, severe delay, refractory myoclonic jerks beginning at age 2 months, and increasing hepatosplenomegaly. He developed corneal clouding and increased gingival hypertrophy and died at age 18 weeks. Autopsy disclosed widespread storage of mucopolysaccharides and lipids within the macrophages and, to a lesser extent, parenchymal cells, of all organ systems. There was extensive demyelination of the cerebral white matter, and dystrophic calcification in the cerebrum, cerebellum, and brainstem. There was no evidence of primary neuronal involvement in the storage. Although the chance concurrence of 2 uncommon diseases is rare, a causal link between the clinical anomalies and the storage disorder cannot be argued convincingly on the basis of one case. Careful pathologic studies of other children who die with clinical signs compatible with Smith-Lemli-Opitz syndrome are indicated.

Malformation syndromes caused by disorders of cholesterol synthesis

“…The second reported case of lathosterolosis was identifi ed by Krakowiak et al ( 209 ). This case was initially reported by Parnes et al ( 212 ) as a mutations are laminopathies rather than inborn errors of cholesterol synthesis.…”

Lathosterolosis: A Disorder of Cholesterol Biosynthesis Resembling Smith-Lemli-Opitz Syndrome

“…It was first reported by Brunetti-Pierri in 2002(Brunetti-Pierri et al 2002. The second case was reported initially as apparent Smith-Lemli-Opitz syndrome by Parnes in 1990(Parnes et al 1990), but was subsequently diagnosed to have lathosterolosis by postmortem examination by Krakowiak et al in 2003(Krakowiak et al 2003. The third case was reported by Rossi in 2007 who followed up on the first case reported by Brunetti-Pierri and described her affected sibling who was a stillborn (Rossi et al 2007).…”

“…To our knowledge, our patient is the first lathosterolosis patient receiving a therapeutic trial of simvastatin. This drug was started at a low dose (0.2 mg/kg/day) and was Each sterol is given in percent of total sterols Table 3 Comparison of clinical features of reported lathosterolosis cases Case 1 (Fetus) (Rossi et al 2007) Case 2 (Brunetti-Pierri et al 2002) (Rossi et al 2007) Case 3 (Krakowiak et al 2003) (Parnes et al 1990) Case gradually stepped up to 1 mg/kg/day. The level of lathosterol successfully decreased from 81.6 mmol/L to 15.1 mmol/L within 4 weeks time (normal level: <18 umol/L) and remained at a relatively low level afterwards.…”

Clinical phenotype of lathosterolosis

“…SLOS patients present with typical facial dysmorphisms, limb anomalies, incomplete development of male genitalia, and malformations possibly involving all organs and systems. Lathosterolosis (LS, OMIM: #607330) is an additional example of this group of metabolic syndromes [Parnes et al, 1990;. Interestingly, the latter case showed massive mucolipidosis-like inclusions [Parnes et al, 1990;Krakowiak et al, 2003], a feature not evident on histological examination of a liver biopsy performed in the first case reported [Rossi et al, 2005].…”