Diagnosis of Sjögren-Larsson Syndrome by Magnetic Resonance Spectroscopy

Abstract

A 25-month-old girl had been born, after an uneventful pregnancy, at 36 weeks of gestation. Her weight was low for her gestational age (2025 g). She was the first child of unrelated and healthy parents. She presented with marked congenital ichthyosis. Motor retardation was later observed (i.e., stable sitting and walking at ages 12 and 22 months, respectively). Her speech was also delayed. Her first clinical evaluation at age 25 months revealed hyperkeratotic ichthyosis, especially at the main flexor folds, with mild facial involvement. The girl manifested severe pruritus. Her hair, nails, and teeth were normal. No organomegaly was evident. A neurologic examination indicated spastic quadriplegia with axial hypotonia and a left convergent strabismus. Cranial magnetic resonance imaging and proton magnetic resonance spectroscopy were performed with a 1.5 T Signa HDXt scanner (General Electric Medical Systems, Milwaukee, WI) (echo times, 35 ms and 144 ms; repetition time, 1500 ms; volume of interest, 8 mL). Cranial magnetic resonance imaging indicated abnormal, hyperintense signals on T2-weighted sequences in the subcortical white matter, predominantly in periventricular areas (Fig 1A). Magnetic resonance spectra were analyzed in the parietal subcortical white matter (Fig 1B), and at various echo times indicated two abnormal peaks compatible with lipid content: one broad and small peak at 0.9 parts per million corresponding to CH3 lipids of the methyl group, and one high and sharp peak at 1.3 parts per million corresponding to (CH2)n lipids of the methylene group (Fig 1C,D). The remaining peaks for N-acetyl aspartate, creatine, choline, and myoinositol appeared normal in shape and relative proportions. The association of congenital ichthyosis with pruritus, spastic tetraplegia, mental retardation, and white-matter hyperintensities on magnetic resonance imaging was highly suggestive of Sjogren-Larsson syndrome. Fibroblast fatty aldehyde/NADþ oxidoreductase activity was not detectable, confirming our diagnosis of Sjogren-Larsson syndrome.