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Case Report

SjogrenLarsson syndrome: Arare

neurocutaneous disorder
Velusamy Subramanian, Praveen Hariharan, J. Balaji
Department of Paediatric Neurology, Institute of Social Paediatrics, Stanley Medical College and Hospital, Chennai, Tamil Nadu,
India

Address for correspondence: Dr.Velusamy Subramanian, 115, Dinesh Street, Paneer Nagar PartII, Mugappair East, Chennai600037,
Tamil Nadu, India. Email:drvelsneuro@yahoo.co.in

ABSTRACT
SjogrenLarsson syndrome is an autosomal recessive disorder characterized by defective activity of fatty aldehyde
dehydrogenase. It presents as a triad of congenital ichthyosis, spastic diplegia, and mental retardation. The
pathology behind this syndrome is the failure of degradation of fatty aldehydes. This case is presented for its
rarity.

Key words: Congenital ichthyosis, fatty aldehyde dehydrogenase, glistening spots in retina, ichthyosis
oligophrenia syndrome, lipid peak, SjogrenLarsson syndrome, spastic diplegia

Introduction
SjogrenLarsson syndrome(SLS)/ichthyosis oligophrenia
syndrome is a rare autosomal recessive disorder with
neurocutaneous manifestations. It is associated with a defective
activity of the enzyme fatty alcohol: NAD+oxidoreductase.[1]
It presents as a triad of congenital ichthyosis, spastic diplegia,
and mental retardation. Excessive fatty aldehydes in SLS
patients form adducts with myelin and accumulate in
stratum corneum and granular cells resulting in various
manifestations of SLS. Alterations in the fundus, speech
defects, short stature, kyphosis of the thoracic vertebral
column, and seizures of varying frequency are described as
secondary symptoms.
Case Report
A 6yearold male child, first born of thirddegree
consanguineous parents, presented with scaly lesions on skin
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over both upper and lower limbs since day 5 of life, global
developmental delay and stiffness of all limbs. The child was
delivered by cesarean section. He was admitted in neonatal
intensive care unit for neonatal jaundice. He had recurrent
episodes of generalized tonic clonic seizures since the age of
1 years with a total of 8 episodes so far(last episode at the
age of 4years).
On examination, diffuse large brown colored diamond
shaped adherent scales were present over the skin of all limbs
implicating generalized ichthyosis with relative sparing of
face [Figure 1]. Seborrheic dermatitis of scalp was present.
Diffuse hyperpigmented macules were present over the
flexural areas and abdominal skin. Kyphoscoliosis of trunk was
present [Figure 2]. On assessment of higher cortical functions,
he had global developmental delay. He is not able to stand
till date. He is able to speak only monosyllables and obeys
simple commands. Central nervous system motor examination
showed spasticity, reduced power(3/5 in lower limbs and
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DOI: Cite this article as: Subramanian V, Hariharan P, Balaji J. Sjogren-

10.4103/1817-1745.181267 Larsson syndrome: A rare neurocutaneous disorder. J Pediatr Neurosci
2016;11:68-70.

68 / 2016 Journal of Pediatric Neurosciences | Published by Wolters Kluwer - Medknow

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Subramanian, etal.: Ichthyosis oligophrenia syndrome
4/5 in upper limbs), exaggerated deep tendon reflexes of
all four limbs, and bilateral plantar extensor. Cranial nerve
examination was normal. There was no sensory deficit or
cerebellar signs. Eye examination revealed ectropion, mildly
congested conjunctiva, and small opacity in the cornea at 8
oclock position. Fundus examination revealed glistening spots
in the foveal and parafoveal region. The triad of congenital
ichthyosis, mental retardation and spastic diplegia arouses
the suspicion of SLS.
Investigations
Magnetic resonance imaging(MRI) brain indicated
bilateral periventricular hyperintensities in parietooccipital
region [Figure 3]. On MR spectroscopy, elevated lipid peak
was noted. Electroencephalogram revealed no epileptiform
activity [Figure 4]. Histopathology of skin lesions revealed
hyperkeratosis, normal dermis with irregular acanthosis
indicating lamellar ichthyosis.
Fatty aldehyde dehydrogenase(FALDH) enzyme activity
in skin fibroblasts and sequence analysis of FALDH gene is
confirmatory(could not be done due to financial constraint).
The child was prescribed emollients for symptomatic relief.
Physiotherapy was advised to relieve spasticity.
Discussion
SLS is an autosomal recessively inherited inborn error of
lipid metabolism. The incidence of the disease is<1 in
Figure1: Brown color diamond shaped adherent scales on the upper limb
and peeling of skin on the lower limb
Figure3: Coronal T1weighted image of magnetic resonance imaging of
brain showing bilateral periventricular hyperintensities
100,000.[2] The disease is caused by mutations in ALDH3A2
gene on chromosome 17p11.2 that encodes fatty alcohol:
NAD+oxidoreductase complex. About 72 mutations in
ALDH3A2 gene have been identified in SLS patients with
missense mutations constituting the highest percentage.[3]
Among the two components (Fatty alcohol dehydrogenase
and FALDH) of the enzyme, there is reduced activity of
FALDH component leading to impaired oxidation of free
toxic aldehyde.[1] FALDH is a Class3 microsomal enzyme
which catalyzes the NADdependent oxidation of aliphatic
aldehydes derived from the metabolism of fatty alcohols,
phytanic acid, ether glycerophospholipids, and leukotriene
B4.[4] FALDH also protects the cells against oxidative stress
induced lipid peroxidation.[5] These accumulated highly
reactive aldehyde substrates are diverted into the production
of other metabolites causing various symptoms.
The disorder presents as ichthyosis soon after birth and
rarely as collodion baby. Ichthyosis is generalized with
sparing of face. Pruritus is usually present. Periumbilical
hyperkeratosis with radiating furrows[6] with palmoplantar
keratoderma may be present. Most common differential
Figure2: Case photograph of SjogrenLarsson syndrome
Figure4: Magnetic resonance spectroscopy of hyperintense lesions
showing abnormally elevated lipid peak
2016 / Jan-Mar / Volume 11 / Journal of Pediatric Neurosciences / 69
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Subramanian, etal.: Ichthyosis oligophrenia syndrome
diagnosis of congenital ichthyosis include harlequin
ichthyosis, Xlinked ichthyosis, and Netherton syndrome.
However, the clinical triad of the syndrome eliminates
the possibilities of other ichthyosiform erythrodermas.
The cutaneous manifestations are the result of abnormal
lipid accumulation in stratum corneum and granular
cells. This leads to leaky dysfunctional water barrier and
hyperkeratosis.[7,8] Pruritus results from elevated levels of
leukotriene B4.[9] Zileuton, 5lipoxygenase inhibitor relieves
this symptom. Prematurity is common due to the inefficient
degradation of Leukotriene B4.
Speech defects, delayed motor milestones, spastic diplegia
or quadriplegia, and mental retardation are the neurological
findings.[10] Excessive fatty aldehydes in SLS patients form
adducts with phosphatidylethanolamine and myelin, thereby
resulting in defects in myelination. MRI generally shows
periventricular hyperintensities, and MR spectroscopy reveals
elevated lipid peaks indicating defect in fatty acid metabolism.
Retinal glistening with white dots in the perimacular region
of the retina on fundus examination is pathognomic of the
disease.[11]
Histopathological features of skin biopsy include
hyperkeratosis and acanthosis consistent with lamellar
ichthyosis. Confirmatory tests include FALDH enzyme assay
in cultured skin fibroblasts and leukocytes and sequence
analysis of ALDH3A2 gene on the locus 17p11.2.[12]
Management is mainly supportive and involves
multidisciplinary approach. Topical emollients, keratolytics,
and oral retinoids provide symptomatic relief. Lowfat diet
early in infancy may improve clinical outcome.[13]
Any case of congenital ichthyosis with spastic paresis and
mental retardation should be evaluated for SLS.
Declaration of patient consent
The authors certify that they have obtained all appropriate
patient consent forms. In the form the patient(s) has/have
given his/her/their consent for his/her/their images and other
clinical information to be reported in the journal. The patients
understand that their names and initials will not be published
and due efforts will be made to conceal their identity, but
anonymity cannot be guaranteed.
70 / Journal of Pediatric Neurosciences / Volume 11 / Jan-Mar / 2016
Acknowledgment
We acknowledge the Department of Radiology, Stanley
Medical College, for MR Spectroscopy.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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