Fucosidosis with Pathogenic Variant in FUCA1 Gene
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SCIENTIFIC LETTER
Fucosidosis with Pathogenic Variant in FUCA1 Gene Vykuntaraju K. Gowda 1
&
Varunvenkat M. Srinivasan 1 & Hemadri Vegda 1 & Maya Bhat 2
Received: 19 August 2019 / Accepted: 10 February 2020 # Dr. K C Chaudhuri Foundation 2020
To the Editor: Fucosidosis is a rare autosomal recessive lysosomal storage disorder characterized by deficiency of alpha – L-fucosidase. Its estimated frequency is below 1 in 200,000 live births. We report two families (F1, F2) with two affected children (F1a, F1b, F2a, F2b), each diagnosed with fucosidosis. Four children, born to consanguineously married couples from two families (F1, F2), three boys and one girl with mean age of 2 y – 6 mo presented with developmental delay followed by regression of milestones. All children had coarse facies, angiokeratomas on palms and soles, and thoracolumbar kyphosis (Fig. 1). We considered clinical differentials of muc opoly sacc harid oses (MPS), S ialidos is, G M1 gangliosidosis and Fucosidosis. Sialidosis and GM1 gangliosidosis will be associated with cherry red spot. Angiokeratomas are seen in Fabry disease also, however, it is not associated with coarse facies. Hence, we suspected Fucosidosis. Urinary glycosaminoglycan (GAG) was absent and X-ray revealed anterior beaking of vertebrae in all children. MRI brain showed hypointensity of globus pallidus, thalami on T2WI with white matter signal changes and
* Vykuntaraju K. Gowda [email protected]; [email protected] 1
Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India
2
Department of Neuroradiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India
mineralization of globus pallidus with splitting on gradient image (Fig. 2). Alpha fucosidase levels were not detected in all children. Targeted exome sequencing identified a homozygous variant c.1057G > T; p.Glu353Ter in FUCA1 gene from F1a and p.E353* on Exon 6 of FUCA1 gene in F2a. Sanger sequencing for variant was positive in homozygous state in F1b and F2b. Parental testing for carrier status revealed that, they were asymptomatic carriers of the same variant in both families. Fucosidosis is characterized by progressive mental and motor deterioration, coarse facies, dysostosis multiplex, angiokeratoma corporis diffusum and seizures [1]. Earlier fucosidosis was classified into type I and type II based on symptoms and age of onset, but current opinion is that the two types are actually a single disorder with signs. The clinical symptoms of type II fucosidosis are similar to, but milder than, those of type I and the presence of angiokeratoma corporus diffusum. All are children belong to type II based on late age of presentation and angiokeratomas [1]. MRI brain in fucosidosis shows global hypomyelination, T2-hyperintense medial and lat-
Indian J Pediatr
Fig. 1 Photograph of the child showing course facies (a, b); angiokeratoma corporis diffusum (c) and kyphosis (d) (Consent taken from the parents to publish the photographs)
Fig. 2 MRI T2WI axial (a
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