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Sjogren-Larsson syndrome: Importance of early diagnosis and aggressive physiotherapy

  • Author(s): Kathuria, Sushruta, MD
  • Arora, Shikha
  • Ramesh, V
  • et al.
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Sjögren-Larsson syndrome: Importance of early diagnosis and aggressive physiotherapy
Sushruta Kathuria MD, Shikha Arora DVD, V Ramesh MD
Dermatology Online Journal 18 (9): 11

Department of Dermatology and STD, Safdarjung Hospital & Vardhaman Mahavir Medical College, Ansari Nagar, New Delhi, India

Abstract

Sjögren-Larsson syndrome (SLS) is a congenital ichthyotic disorder with spasticity. We describe a case of a 5-year-old boy with SLS diagnosed clinically based on congenital ichythosis, quadriplegia, and mental retardation. The child responded well to emollients and antihistamines. His quadriplegia was managed by aggressive physiotherapy and mental retardation by stimulation techniques. After a 3-year follow up, significant improvement was seen in his motor and mental disability. This case highlights the importance of clinical diagnosis and early intervention for such a disabling disorder.


A 5-year-old boy, born of non-consanguineous marriage, presented 3 years previously with generalized scaling since birth, itching, and collodion membrane at birth. There was no history of erythroderma, seasonal variation of scaling, vesicobullous lesions, cyclical shedding of scales, atopy, or photosensitivity. At age of 10 days, the child had single episode of generalized seizures associated with hypocalcemia, which resolved with treatment. Family history of similar complaints was absent.


Figure 1Figure 2
Figure 1. Generalized ichthyosis with accentuation at flexures and umbilicus

Figure 2. Skin biopsy (H&E x10): Orthohyperkeratosis with normal granular layer

Cutaneous examination showed generalized scaling without erythema and relative sparing of the genitalia, thighs, and buttocks. The scales were small over the forehead, trunk, and arms and were larger over the preauricular area, axillae, forearms, and legs with accentuation at flexures and umbilicus (Figure 1). Mild palmar keratoderma was present. All developmental milestones were delayed at 2 years of age, when the child was brought to us. The child could not sit or stand even with support and had scissoring of the lower limbs. Spasticity was present in all four limbs. He had difficulty in understanding parents’ commands. The weight and height were below the 50th percentile. IQ assessment by Development Assessment scale revealed mild mental retardation. Skin biopsy showed orthohyperkeratosis, acanthosis, papillomatosis, normal granular cell layer, and mild upper dermal inflammatory infiltrate (Figure 2). On CECT head, leukodystrophy was present. A diagnosis of Sjögren-Larsson syndrome (SLS) was made based on the classic triad of congenital ichthyosis, spastic quadriplegia, and mental retardation, collodion membrane at birth, pruritus, leukodystrophy on CECT, and compatible histopathology.

The ichthyosis was treated with emollients and antihistamines. Aggressive physiotherapy was started for limb spasticity, which was the major concern. The child was encouraged to walk with a walker and an ankle orthosis was applied. Mental retardation was managed by stimulation techniques including milestone- accelerating activities and play therapy. Over the past 3 years, there has been significant improvement in scaling and itching. His social skills have improved; he interacts with people including strangers. He understands simple commands and is more active and playful. The most promising improvement is seen in the spasticity of his limbs. There has been a 90-100 percent improvement in upper limb spasticity and a 50 percent improvement in spasticity of the lower limbs. He is now able to stand with support on his toes. Scissoring is seen occasionally. No fixed deformities or contractures have developed which would have been inevitable in the absence of physiotherapy. Physiotherapy of the lower limbs is continued because he is not able to stand on his own.

Sjögren-Larsson syndrome is a rare, fully penetrant autosomal recessive disorder characterized by a triad of congenital ichthyosis, spastic diplegia, and mental retardation, often associated with leukodystrophy and ophthalmological changes such as foveal white dots [1]. It is caused by deficiency of fatty aldehyde dehydrogenase (FALDH) that catalyses conversion of fatty alcohol to fatty acid and leads to accumulation of fatty aldehydes in skin, liver, central nervous system, and muscles leading to various symptoms. The defect is seen on the short arm of chromosome 17 [1]. Various mutations are known worldwide, but in an Indian family, c.142G>T (p.Asp48Tyr) in exon 1 of the coding region of ALDH3A2 is reported [2]. This child was born of a non-consanguineous marriage and his condition could relate to spontaneous mutation [2].

Ichthyosis in SLS is present at birth, with exaggeration at flexures and neck, relative sparing of central face, and moderate to severe pruritus [3, 4] as seen in this child. Hypohidrosis [3] and macular dystrophy were absent, but need not be a consistent feature in all patients. The entities in the differential diagnosis include other ichthyotic syndromes with neurological involvement such as neutral lipid storage disorder, hystrix-like-ichthyosis and deafness syndrome, and multiple sulphatase deficiency syndrome. However, none of these have spastic diplegia, which is characteristic of SLS. Mutation analysis, FALDH, and FAO enzyme (a component of microsomal fatty alcohol: NAD oxidoreductase) activity in cultured fibroblasts or leukocytes, urinary concentrations of leukotriene(LT)B4 and 20-OH-LTB4, which can help confirm the diagnosis, could not be assessed because of unavailability in our setup.

Mild to moderate ichthyosis is treated with emollients and keratolytics and systemic retinoids are used in severe ichthyosis. Dietary modifications such as reduced fat intake to <30 percent of total caloric intake, supplementation with canola oil, and increasing unsaturated fatty acids, as adjunctive therapy, has also shown improvement in ichthyosis and pruritus, but has not had significant affect on the neurological symptoms [1]. Mild to moderate pruritus responds to antihistamines but persistent pruritus can be treated with zileuton, a leukotriene inhibitor. Almost all patients of SLS are known to develop contractures, deformities, and inability to stand or walk in time [5, 6]. Initial early intervention includes physiotherapy and once physiotherapy is ineffective, surgery remains the mainstay of treatment [6]. Passive and active exercises, rollator, ankle orthosis, and mental stimulation techniques were used in this case and there was significant improvement in quality of life.

This case report highlights that early recognition of SLS is important so that aggressive physiotherapy can be started to avoid long-term contractures, spasticity, and surgery. Ichthyosis is a significant clinical finding and most patients of SLS present initially to the dermatology department [6]. As a dermatologist, early onset ichthyosis with pruritus and spasticity should raise a high clinical suspicion of SLS. Clinical symptoms by themselves are quite suggestive of the diagnosis.

References

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2. Sakai K, Akiyama M, Yanagi T, Nampoothiri S, Mampilly T, Sunitha V, Shimizu H. An Indian family with Sjögren-Larsson syndrome caused by a novel ALDH3A2 mutation. Int J Dermatol. 2010; 49:1031-3. [PubMed]

3. Willemson MAAP, IJ1st L, Steijlen PM, Rotteveel JJ, de Jong JGN, van Domburg PHMF, etal. Clinical, biochemical and molecular genetic characteristics of 19 patients with Sjögren-Larsson syndrome. Brain 2001; 124: 1426-37. [PubMed]

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6. Haddad FS, Lacour M, Harper JI, Fixsen JA. The orthopaedic presentation and management of Sjögren-Larsson syndrome. J Pediatr Orthop. 1999; 19: 617-9. [PubMed]

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