Extensive Mongolian spots: A clinical sign merits special attention
Extensive Mongolian spots
A clinical sign merits special attention
M.R.Ashrafi1, R.Shabanian2, M.Mohammadi3, S.Kavusi4
Department of Pediatric Neurology, Children’s Medical Center, School of
Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Authors:
1. Mahmood Reza Ashrafi: Associate Professor of Pediatric Neurology, Tehran
University of Medical Sciences, Children’s Medical Center, Tehran, Iran.
2. Reza Shabanian: Pediatric Resident, Tehran University of Medical Sciences,
Children’s Medical Center, Tehran, Iran.*
3. Mahmood Mohammadi: Professor of Pediatric Neurology, Tehran University of
Medical Sciences, Children’s Medical Center, Tehran, Iran.
4. Susan Kavusi: Assistant Professor of Dermatology, Tehran University of
Medical Sciences, Razi Hospital, Tehran, Iran.
*
Corresponding Author: Reza Shabanian, Pediatric Resident, Tehran University of Medical
Sciences, Department of Pediatric Neurology, Children’s Medical Center, 62 Gharib Street,
14194, Tehran, Iran
Tel: 98-912-219-1726
Fax: 98-21-693-0024
Email: rshabanian@gmail.com
Academic degrees for persons listed in acknowledgment section
Mina Izadyar: Assistant professor of pediatric hematology and oncology
Javad Jannati: Assistant professor of radiology
Nasrin Ghandi: Dermatology resident
Category: case report
Abstract & Key words
Main Text (introduction, case report, Discussion)
Acknowledgements
References
Legends for illustrations
Illustrations
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Extensive Mongolian spots: A clinical sign merits special attention
Extensive Mongolian spots
A clinical sign merits special attention
Abstract
Although typical and limited Mongolian spots are benign skin markings at birth
which fade and disappear as the child grows, extensive Mongolian spots deserve
special attention as possible indications of associated inborn error of metabolism.
A few cases of extensive Mongolian spots in association with inheritable storage
diseases have been reported. Some hypotheses have been put forward, but
further investigation is necessary to elucidate the causative factors. We describe
3 infants with generalized Mongolian spots, two infants with GM1gangliosidosis
type1 and one in association with Hurler syndrome. Findings of generalized
Mongolian spots in newborns may lead to an early detection and early treatment
before irreversible organ damage occurs.
Keywords: Mongolian spots, inborn error of metabolism, GM1gangliosidosis,
Hurler syndrome, dermal melanocytosis.
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Extensive Mongolian spots: A clinical sign merits special attention
Introduction
Mongolian spots are blue or slate-gray macular lesions occurring most
commonly in the sacral area but also found over posterior thighs, legs, back and
shoulders. They may be solitary or numerous. Generalized or extended
Mongolian spots involve large areas over the entire posterior and anterior
aspects of the trunk and extremities. Mongolian spots usually fade during the first
few years of life but they occasionally persist. Those associated with inborn error
of metabolism (IEM) such as GM1gangliosidosis and Mucopolysaccharidosis
show no sign of resolution. They may also become heavier in their colors [1, 2,
3]. The potential association of generalized Mongolian spots with inheritable
storage disease has been described but still their relationship is poorly
understood. We describe 3 infants with generalized Mongolian spots in
association with IEM.
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Extensive Mongolian spots: A clinical sign merits special attention
Case report
Case1. A male infant who was born to consanguineous parents after a normal
vaginal delivery was seen at the age of 12 months for delayed developmental
milestones. He had coarse face, frontal bossing, hepatosplenomegaly, bilateral
inguinal hernia and widespread Mongolian spots extending over the back and
upper and lower extremities (Fig 1). He had an exaggerated startle response to
noise. Skeletal bone survey showed paddle- shaped ribs, beaking of lumbar
vertebral bodies and flaring of iliac wings resembling skeletal abnormalities seen
in mucopolysaccharidosis. Liver function tests showed elevated transaminases.
Urine was negative for mucopolysaccharides. BMA revealed numerous foamy
cells (sea blue histiocytes) in favor of storage disease. Skin biopsy showed
dermal spindle cell melanocytic proliferation associated with focal ectasia
(Fig
2). Cherry red spot was seen in fundoscopic examination. galactosidase
activity in leukocytes was absent. He had GM1gangliosidosis.
Case2. A 15-month-old boy of consanguineous parents came to observation
due to neurodevelopmental regression. In physical examination he had coarse
facial
feature
hepatosplenomegaly,
kyphosis,
bilateral
umbilical
hernia,
nystagmus, spasticity, psychomotor retardation and extensive Mongolian
spots. Skeletal bone survey showed osteoporosis, paddle shaped ribs and
beaking of a lumbar vertebral body. In fundoscopy he had cherry red spot of the
retina. The report of numerous foamy cells in bone marrow aspiration supported
a diagnosis of storage disease (Fig 3). galactosidase activity was undetectable
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Extensive Mongolian spots: A clinical sign merits special attention
in peripheral leukocytes consistent with the diagnosis of GM1gangliosidosis
type1. He died five months later.
Case 3.The third patient was a five–month-old male infant, product of
nonconsanguineous parents, presenting with recurrent upper respiratory tract
infection, persistent noisy breathing and vomiting after breast feeding. Two
siblings died at 8 months of age due to cardiac complication probably
cardiomypopathy. He had coarse facial features, wide-apart eyes, and a
depressed nasal bridge. He also had harsh breath sounds, hepatosplenomegaly,
right inguinal hernia and extensive blue Mongolian spots on the back, buttock
and distal extremities. Echocardiography showed cardiomayopathy. Urine
analysis for MPS was positive. He had corneal clouding. Cherry red spot was not
seen in retinal examination. Bone marrow aspiration was unremarkable. Enzyme
assay established the definitive diagnosis of MPS (Hurler syndrome). He died
because of infection 45 days after bone marrow transplantation.
Parents of these three patients expected that these blue spots would fade and
disappear with passing time (according to their physicians’ prognoses), but in
these cases the Mongolian spots neither faded nor disappeared. Furthermore, in
two cases, the spots became darker. .
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Extensive Mongolian spots: A clinical sign merits special attention
Discussion
Mongolian blue spots or dermal melanocytosis are birth marks with wavy
borders and irregular shapes [3, 4]. Among different ethnic groups, over 90% of
Native Americans and people of African descent, about 80% of Asians, about
70% of Hispanics and fewer than 10% of Caucasians have Mongolian spots [4].
A study in 1976 showed the presence of Mongolian spots in about 40% of Iranian
newborns [5]. The sacral area is the classic site of involvement. Typical and
limited Mongolian spots are benign skin markings, commonly appear at birth or
shortly after, and are not associated with any disorder .They generally fade in a
few years and disappear by puberty. However, extensive Mongolian spots which
involve large areas of the posterior and anterior aspect of the trunk and
extremities deserve special attention. A retrospective review of the literature
revealed that the combination of extensive Mongolian spots and inborn error of
metabolism may not be coincidental [1, 3, 6].
This is the first case report from Iran since 1981, when Weissbluth et al first
recognized the relationship between IEM and extensive Mongolian spots [7]. By
reviewing the last 10 years’ medical records of patients admitted in Children
Medical Center that is a referral center for pediatric neurometabolic disorders in
Iran, we did not find any report of extensive Mongolian spots associated with
IEM. This may be due to the belief that Mongolian spot is a benign skin marking
with high prevalence in Asian newborns. It is obvious that a comprehensive study
is necessary to follow infants with extensive and ectopic Mongolian spots for
IEM, to determine the association and the predictive value of this clinical sign.
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Extensive Mongolian spots: A clinical sign merits special attention
The most common lysosomal storage disease associated with generalized
Mongolian spots is Hurler syndrome followed by GM1gangliosidosis type1 [3]. A
literature review revealed 39 cases of lysosomal storage disease associated with
dermal melanocytosis. 24 cases had Hurler disease and 11 patients were
suffered from GM1gangliosidosis type1 [3]. An association with Niemann_pick
disease, hunter and _mannosidosis was also reported [1, 3, 8, 9, 10]. In these
conditions hyperpigmentation is a long–lasting symptom.
Histopathologic
examination
of
skin
lesion
shows
elongated
dermal
melanocytes with fine melanin pigment. Electron microscopic examination shows
that the dermal melanocytes are similar to those seen in the developmental stage
of common Mongolian spots in normal infants [3, 8]. In cases of lysosomal
storage disease, ultra structural features of melanocytes in the biopsy specimen
from unaffected skin show a higher concentration of empty lysosomal vacuoles
compared to menalocytes of lesional skin. It is assumed that with the progressive
accumulation of metabolites and neurological deterioration, the lysosomal
vacuoles are simply displaced or reabsorbed as melanocytes activation continue
to progress in the affected skin. Mongolian spots result from entrapment of
melanocytes in the dermis because of arrested transdermal migration from the
neural crest into the epidermis. Exogenous peptide growth factors through
activation of receptors with tyrosin kinase properties regulate this migration.
Some experts noted that accumulated metabolite such as GM1 and heparan
sulfate bind to this tyrosin kinase-type receptor (Trk) which enhances nerve
growth factor activity and leads to both severe neurologic manifestation and
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Extensive Mongolian spots: A clinical sign merits special attention
aberrant neural crest migration. Since melanocytes have chemotropic receptors
for nerve growth factor, metabolite-Trk binding may lead to arrested melanocytes
transdermal migration. However further investigation is necessary to confirm the
role of growth factors (e.g. hepatocyte growth factors) and Homebox gene in the
pathogenesis of dermal melanocytosis [3].
Better prognoses in cases with early application of stem cell transplantation or
recombinant enzyme therapy emphasize the importance of early diagnosis in
children before irreversible organ damage occurs. A proven clinical correlation
could lead to early diagnosis and treatment of IEM in these patients with
extensive Mongolian spots, identification of at-risk families, and prevention of
complications. Proving this correlation will require more cases to be reported and
more comprehensive investigations. If this correlation is proved in future, a
workup for inborn error of metabolism will be necessary for all newborns with
extensive Mongolian spots. Until that time, close observation of patients with
extended and ectopic Mongolian spots, especially in cases with positive family
history, seems to be useful.
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Extensive Mongolian spots: A clinical sign merits special attention
Acknowledgements
We appreciate Dr. Mina Izadyar MD, Dr Javad Jannati MD and Dr Nasrin Ghandi
MD for their help and cooperation.
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Extensive Mongolian spots: A clinical sign merits special attention
References
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2. Ochiai T, Ito K, Okada T, Chin M. Significance of extensive Mongolian spots in
Hunter’s syndrome. British J of Dermatology 2003; 148:1173-78.
3.Hanson M, Lupski J, Hicks J, Metry D. Association of dermal melanocytosis
with lysosomal storage disease. Arch Dermatology 2003; 139:916-920.
4. Jacobs AH, Walton RG.The incidence of birthmarks in the neonate. Pediatrics
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5. Valizadeh G. Mongolian spots and its prevalence in Iranian newborns .J of Iran
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to Hurler disease. Ann Dermatol Venerol 1999; 126(1):35-7.
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Weissbluth
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with
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syndrome .J Am Acad Dermatol 1998; 39:1013-15.
9 Camur S, Coskun T, Kiper N. Alpha-mannosidosis :The first Turkish case .
Acta Paediatr Jpn 1995; 37:230-232.
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Extensive Mongolian spots: A clinical sign merits special attention
Legends for illustrations
Fig 1- Generalized Mongolian spots over the back and also upper and lower
extremities of an infant with GM1gangliosidosis type 1.
Fig 2-Skin biopsy obtained from blue spots showing dermal spindle cell
melanocytic proliferation (black arrows) with focal ectasia in an infant with
GM1gangliosidosis type1.
Figure 3–Foamy cell or sea blue histiocyte (black arrow) in the bone marrow
aspiration of an infant with GM1 gangliosidosis type1.
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