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Citation: Ede Daar G, Baysoy G, Demir H, Kurtoglu S, Coşkun T. Metabolic cardiomyopathy in GM1 gangliosidosis: Worse prognosis factor?
Jr.med.res.2021;4(1): 7-9. Ede Daar et al © All rights are reserved. https://doi.org/10.32512/jmr.4.1.2021/7.9
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Case report
Ede Daar Ghaniya
1, *
, Baysoy Gokhan
2
, Demir Hülya
2
, Kurtoglu Selim
3
, Coşkun Turgay
4
.
Metabolic cardiomyopathy in GM1 gangliosidosis: Worse prognosis factor?
1: Department of Pediatrics, Neonatology unit,
Sidra Medicine, Doha, Qatar
2: Department of pediatric Gastroenterology
Hacettepe University, Ankara, Turkey
3: Department of Pediatrics, Erciyes University,
Neonatology Unit, Kayseri, Turkey
4: Department of Pediatrics, Metabolic Diseases
Unit,Hacettepe University, Ankara, Turkey
* Corresponding author
Correspondence to:
gede@sidra.org
Publication Data:
Submitted: March 28,2021
Accepted: May14,2021
Online: May 30,2021
This article was subject to full peer-
review.
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GM1 gangliosidosis is an autosomal recessive lysosomal storage disorder due to
deficiency of the β-galactosidase enzyme which hydrolyzes the terminal β-galactosyl
residues from GM1 ganglioside, glycoproteins, and glycosaminoglycans. Patients
with infantile GM1 gangliosidosis present at birth or shortly thereafter with visceral
changes and severe neurological deterioration leading to early death. In this report,
we presented a case of infantile GM1 gangliosidosis associated with multiple
organomegaly.
Keywords:
Infant; cardiomyopathy; GM1 gangliosidosis.
Introduction
Three clinical forms of GM1 gangliosidosis are recognized: infantile-, juvenile-, and
adult-onset forms. The β-galactosidase activity in affected individuals correlates with
disease onset. The infantile form is usually fatal within the first 2 years of life.
Metabolic cardiomyopathies develop as a result of impaired energy-producing
pathways concerning carbohydrate, fat, and mucopolysaccharide metabolism [1].
However, cardiomyopathy due to infantile GM1 gangliosidosis is related to disturbed
elastogenesis and elastin-binding protein defects [2].
Metabolic infantile GM1 gangliosidosis cardiomyopathy has been rarely reported [3].
Herein we report a new case of in 4-month-old boy. The aim is to highlight clinical,
pathological and prognostic characteristics of this entity.
Observation
A 4-month-old boy was referred to us for hepatosplenomegaly, nephromegaly, and
cardiomegaly. The infant was born from consanguineous marriage after 38 weeks
of unremarkable gestation. On his family history, we noted high rate of cardiac-
related child death among first-degree siblings. Physical examination on admission
revealed a height of 75 cm (at 97th percentile), weight of 7400 g (75th -90th
percentile) and head circumference was 43 cm (50th -75th percentile for age).
The baby had tachycardia, mild tachypnea with shortness of breath. He had a coarse
facial feature, hepatosplenomegaly, scrotal angiokeratoma, bilateral hydrocele and
large gluteal Mongolian spots. Neurological examination revealed hypotonia, with a
lack of head control, could not sit with support. The fundoscopic examination was
normal.
Laboratory analyses revealed mild anemia, elevated liver transaminases, high
alkaline phosphatase, and lactate dehydrogenase values. Blood lactate, pyruvate,
and amino acid values were normal. Thyroid function test, creatinine kinase, blood
gas, and urine analysis were normal. Tandem mass spectrometry of blood was
negative for amino acid and acylcarnitine abnormalities. Peripheral blood smear
findings were normal. Bone marrow aspiration was normocellular with foamy cells
(Figure a). Lysosomal enzymes (sphingomyelinase and glucosylceramidase) were
normal except for β-galactosidase, which showed only 1.48 nmol/hr/mg protein
activity in the lactates (normal range 107.3±35.8).
Abstract
Metabolic cardiomyopathy in GM1 gangliosidosis: Worse prognosis factor?
Citation: Ede Daar G, Baysoy G, Demir H, Kurtoglu S, Coşkun T. Metabolic cardiomyopathy in GM1 gangliosidosis: Worse prognosis factor?
Jr.med.res.2021;4(1): 7-9. Ede Daar et al © All rights are reserved.
Submit your manuscript: www.jmedicalresearch.com.
8
Chest X-ray showed a cardiac/thoracic ratio of 0.8 and pulmonary congestion (Figure b). Anterior beaking of the
vertebral bodies was noticeable. Abdominal ultrasonography revealed hepatosplenomegaly and bilateral nephromegaly.
Echocardiography showed dilatation of all four cavities specially the left ventricle with poor contractility and ejection
fraction of 57% (Figure c). Electrocardiography revealed hypertrophy of the left ventricle and left axis deviation.
Treatment for cardiac failure was initiated. The patient died 10 months later due to severe congestive decompensation.
a b c
Figures:
a: Bone marrow examination showing foamy cell proliferation.
b: Chest X-ray showing visible anterior beaking of the vertebral bodies.
C: Echocardiography showed dilatation of the four cardiac cavities with poor contractility
Discussion
GM1 gangliosidosis is a neuronopathic lysosomal storage disorder caused by a deficiency in the enzyme β-galactosidase
related to GLB1 gene mutations. This enzyme is responsible for the degradation of GM1 ganglioside, oligosaccharides,
and keratan sulfate. This disorder leads to lysosomal accumulation of the GM1 ganglioside and other galactose-
containing glycoconjugates [4,5]. GM1 gangliosidosis is ultra-rare disease with an estimated incidence of 1 in 100,000-
200,0000 live births [6]. The residual activity of the mutant β-galactosidase enzyme, organ distribution and the
importance of material accumulation determine the clinical classification of infantile (type 1), juvenile (type 2), and
adult (type 3) forms. The infantile form is characterized by absent mutant enzyme activity with progressive neurologic
deterioration, sensorimotor and psycho-intellectual dysfunction. The evolution is usually fatal within 3 years of life [7].
The prenatal diagnosis of GM1 gangliosidosis is still difficult because of the non-specificity of the related
ultrasonographic abnormalities [8]. typically, cherry-red spots at the macula, facial dysmorphism, hepatosplenomegaly,
neurologic degenerative disorder, and generalized skeletal dysplasia are hallmarks of the disease. Diagnosis is
confirmed by the assessment of the β-galactosidase activity [9].
Cardiac involvement rarely associated with GM1-gangliosidosis. Some mutations of the GLB1 are common to the
lysosomal enzyme and the elastin binding protein (EBP). Consequently, this form of the disease may present more
musculoskeletal and cardiac specific manifestations [10]. The cardiac involvement may worsen the prognosis and
accelerate the fatal evolution by hemodynamic disorder and bronchopulmonary recurrent infections.
Conflict of Interest: None
Metabolic cardiomyopathy in GM1 gangliosidosis: Worse prognosis factor?
Citation: Ede Daar G, Baysoy G, Demir H, Kurtoglu S, Coşkun T. Metabolic cardiomyopathy in GM1 gangliosidosis: Worse prognosis factor?
Jr.med.res.2021;4(1): 7-9. Ede Daar et al © All rights are reserved.
Submit your manuscript: www.jmedicalresearch.com.
References
[1] Sanchez-Fernandez EM, Garcia Fernandez JM, Mellet CO. Glycomimetic-based pharmacological chaperones for lysosomal storage disorders: lessons from Gaucher, GM1-
gangliosidosis and Fabry diseases. Chem Commun (Camb) 2016; 52:5497-15.
[2] Karimzadeh P, Naderi S, Modarresi F, Dastsooz H, Nemati H, Farokhashtiani T, et al. Case reports of juvenile GM1 gangliosidosisis type II caused by mutation in GLB1 gene.
BMC Med Genet. 2017; 18:73.
[3] Bouhouche A, Tibar H, Kriouale Y, Jiddane M, Smaili I, Bouslam N, et al. Genetic Analysis of Undiagnosed Juvenile GM1-Gangliosidosis by Microarray and Exome Sequencing.
Case Rep Genet. 2018; 2018:8635698.
[4] Lang FM, Korner P, Harnett M, Karunakara A, Tifft CJ. The natural history of Type 1 infantile GM1 gangliosidosis: A literature-based meta-analysis. Mol Genet Metab. 2020;
129:228-35.
[5] Arash-Kaps L, Komlosi K, Seegräber M, Diederich S, Paschke E, Amraoui Y, et al. The Clinical and Molecular Spectrum of GM1 Gangliosidosis. J Pediatr. 2019; 215:152-57.
[6] Tonin R, Caciotti A, Procopio E, Fischetto R, Deodato F, Mancardi MM, et al. Pre-diagnosing and managing patients with GM1 gangliosidosis and related disorders by the
evaluation of GM1 ganglioside content. Sci Rep. 2019; 9:17684.
[7] Regier DS, Proia RL, D'Azzo A, Tifft CJ. The GM1 and GM2 Gangliosidoses: Natural History and Progress toward Therapy. Pediatr Endocrinol Rev. 2016; 13:663-73.
[8] Sinelli MT, Motta M, Cattarelli D, Cardone ML, Chirico G. Fetal hydrops in GM (1) gangliosidosis: a case report. Acta Paediatr. 2005; 94:1847-9.
[9] Lawrence R, Van Vleet JL, Mangini L, Harris A, Martin N, Clark W, et al. Characterization of glycan substrates accumulating in GM1 Gangliosidosis. Mol Genet Metab Rep. 2019;
21:100524.
[10] Morrone A, Bardelli T, Donati MA, Giorgi M, Di Rocco M, Gatti R, et. Beta-galactosidase gene mutations affecting the lysosomal enzyme and the elastin-binding protein in
GM1-gangliosidosis patients with cardiac involvement. Hum Mutat. 2000; 15:354-66.
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