By the Time She Diagnosed with GM1 Gangliosidoses She Is No More: Case Presentation

Journal of Perinatal, Pediatric and Neonatal Nursing Volume 1 Issue 1

By the time she diagnosed with GM1 Gangliosidoses she is no more: Case Presentation

1Samundy Kumbhakar, 2Aravind Singh 1Faculty of OBG department, College of Nursing, Uttar Pradesh University of Medical sciences, Saifai, Etawah, Uttar Pradesh, India 2 Faculty of Medical Surgical Department, College of Nursing, Uttar Pradesh University of Medical sciences, Saifai, Etawah, Uttar Pradesh, India Email: [email protected]

Abstract Beta-galactosidase-1 deficiency is rare lysosomal storage disorder which is also called as GLB1 deficiency or Landing disease. It is an autosomal recessive disorder whose age of onset is usually child hood. Deficiency of beta – galatosidase enzyme due to mutations of GLB1 gene results in toxic accumulation of gangliosides in either body tissues or particularly in the central nervous system which ultimately ends up in neurovisceral, ophthalmological and dysmorphic features. The types of GM1 gangliosidosis is based on the age of onset; infantile form which is severe and rapidly progressive, a late infantile or juvenile form with onset usually from seventh month to 3 years of age accompanied with delayed motor and cognitive development and thirdly an adult or chronic form with late onset characterized by generalized dystonia. The severity of disease depends on the level of beta – galactosidase activity. Due to the wide spectrum of disease, the diagnosis may be difficult. Facial coarsening, hypertrophic gums, cherry -red macula, visceromegaly, dysostosis and psychomotor are some signs of storage disorders which may help to diagnose GM1 gangliosidosis. The confirmative diagnosis is biochemical assay of beta – galactosidase activity by molecular genetic testing. GLB1 molecular analysis can be done either by chorionic villus or amniotic cells as prenatal diagnosis. There is no specific treatment for GM1 gangliosidosis; treatment is symptomatic as well as supportive. Extremely poor prognosis found in severe infantile form.

Key Terms: GM1 Gangliosidosis, Beta-galactosidase-1 deficiency, landing disease, GLB1 deficiency, β -galactosidase-1 deficiency, Lysosomal disorders

INTRODUCTION (1/27) have an increased risk with a carrier GM1 gangliosidosis is broadly classified state compared to Irish/ British Isle (1/50 under lysosomal storage disorder. It is an to 1/150) [5]. Lysosomal storage disorders inherited autosomal recessive disorder that include nearly 50 different diseases with a gradually degenerates nerve cells combined incidence of 1:1500 to 1:7000 (neurons) in the brain and spinal cord births. Prevalence of GM1 among Maltese [1,2]. Absence or significantly reduced Islands is 1:3,700, Roma ancestry is level of vital enzyme called beta – 1:10,000, and from Brazil is 1:17,000 [6]. galactosidase cause GM1 gangliosidosis Studies have proved that siblings are prone [3,4]. Each child has 25% of having the to get GM1 Gangliosidosis. For instance, disease if both the parents are carriers. In Gascon et al. (1992) reported that two general population, the carrier rate is Saudi Arab siblings (brother and sisters of 1/250. Natives of French Canadians, 9 and 7 years respectively) were diagnosed Louisiana Cajuns and Ashkenazi Jews with GM1 Gangliosidosis and presented

Journal of Perinatal, Pediatric and Neonatal Nursing Volume 1 Issue 1

with developmental arrest, gait disturbance manifestations. Also, gastro intestinal and dementia. In addition, both were disorders like hepatosplenomegaly at confined to bed by 2 years of age, had around 6 months, distended abdomen; progressive myoclonic epilepsy syndrome muscle weakness; macular cherry red spots with hyperacusis and in due course, they in the eye by 6- 10 months or corneal had spastic quadriparesis which led to a opacities and deaf and blind by age 1 and decerebrate state. The CT scans revealed hyperacusis (increased sensitivity to global brain atrophy and the deficiency of certain frequency) may be present in child. ß-galactosidase activity was confirmed by Over and above facial dysmorphology, bone marrow biopsies. They had another frontal bossing, wide nasal bridge, facial sibling with same complaints but passed edema or puffy eyelids, peripheral edema, away at the age of three [7]. epicanthus, long upper lip, microretrognathia, gingival hypertrophy Based on the onset or the first appearance (thick alveolar ridges), macroglossia, of the clinical manifestation, GM1 developmental regression (losing acquired gangliosidoses are classified as type 1 - skills) and profound intellectual disability early or classic infantile, type 2 - late are also seen. The child may die due to infantile or juvenile or type 3 - adult or cardiac complication or pneumonia/ chronic [8]. The child with type 1 or early respiratory failure [12]. infantile usually doesn’t survive beyond infanthood [2,9]. Neurodegeneration, Type 2 involves intermediate form of convulsions, exaggerated startle response, condition and hence, includes late infantile early psychomotor deterioration such as (around 18 months) or juvenile forms (3 - decreased activity, lethargy in the first 5 years) [12]. Usually these children have weeks like initial hypotonia (hypotonic normal development initially, later develop infant with regression in milestones and developmental regression, distinctive hepatomegaly occur not only in facial features, or enlarged organs. Even gangliosidoses (i.e., GM1 type I, Tay- though type 2 progresses are slower than Sachs, Sandhoff, fucosidosis, α- type 1, but still it causes a shortened life mannosidosis) but also in mucolipidoses expectancy. Type 3 is adult or chronic (i.e., sialidosis, I-cell disease, multiple form as the onset is between 3 and 30 sulfatase deficiency), years and represents the mildest end of the mucopolysaccharidoses (i.e., Hurler disease. Furthermore, muscle atrophy syndrome), and glycogen storage leading to dystonia (involuntary tensing of disorders (i.e., Pompe disease)[10,11], various muscles), abnormalities of the followed by spasticity, delayed milestones, spinal cord, corneal clouding and feeding problems, visual failure by 6 angiokeratomas are also found. months, secondary microcephaly, decerebrate rigidity by 1 year are Acid β -galactosidase genotyping neurological signs of GM1 gangliosidosis. (molecular diagnosis of the beta – 1 In addition, skeletal abnormalities, galactosidase gene - GLB1) to detect particularly, joint stiffness, flexion heterozygous carriers and affected patients contractures by 3 months, early [13,14], lumbar puncture to rule out subperiosteal bone formation, diaphyseal GM1 ganglioside levels which may be widening later, demineralization, increased in CSF, skin biopsy to establish thoracolumbar vertebral hypoplasia acid β -galactosidase activity in cultured leading to fracture around age 3–6 months; fibroblasts, prenatal diagnosis such as kyphoscoliosis, dysostosis multiplex are amniocentesis or chorionic villi testing to some of the initial stage clinical find β -galactosidase activity in cultured

Journal of Perinatal, Pediatric and Neonatal Nursing Volume 1 Issue 1

amniocytes or amniotic chorionic villi, the [14]. Presence of Galactosyl- screening test includes acid β - oligosaccharides in amniotic fluid with galactosidase activity in peripheral blood high-performance liquid chromatography leukocytes, not opted for the screening of (HPLC) at 14 weeks gestation may help to heterozygote carriers as an overlap is often diagnose GM1 gangliosidosis prenatally present between homozygotes without [16]. GM1 gangliosidosis and heterozygote carriers, an ancillary diagnostic test for CASE PRESENTATION galactose-containing oligosaccharides in This is 27 years old female with obstetric urine, Complete Blood Count for Score G1P0L0A0 presented with meconium Vacuolation of lymphocytes (nonspecific stained liquor and delivered a single live indicator in lysosomal storage disorders) term female baby with APGAR 7 and 9 at and dried blood spots from new born 1 and 5 minutes by Caesarean Section. screening filter paper (even after 15 Both couples had family history of infant months in storage enable to diagnose)[15]. death with unidentified cause. Although Skeletal radiographs may reveal dysostosis she had history of mild anaemia since multiplex including thickened calvaria, J- childhood, she was diagnosed to have shaped enlarged sella turcica, wide minor thalassemia. spatula-shaped ribs, flared ilia, acetabular dysplasia and flat femoral heads, wide MANAGEMENT AND OUTCOMES wedge-shaped metacarpals, shortened long Currently, there is no particular bones with diaphyseal widening, and management for GM1 gangliosidosis. hypoplastic and anteriorly beaked Although symptomatic treatment could thoracolumbar vertebrae. Delayed bone help to reduce neurologic signs and age also may be demonstrated. In the adult symptoms but then does not significantly form, only mild vertebral changes may be alter the progression of the condition. observed [14]. Neuroimaging by CT scan Mostly, the principle of treatment includes or MRI generally reveals diffuse atrophy restoring the missing enzyme or and white matter demyelination with or decreasing the waste accumulation [1]. without basal ganglia changes. Bilateral Within 24 hours of the birth, the child had T2-weighted hyperintensities in the generalized convulsions and was referred putamen are a frequently reported MRI to NICU. After blood investigations, the finding in adult-onset disease. Mild child was diagnosed with imbalanced cerebral atrophy may also be observed in electrolytes, particularly potassium and the adult form. MR spectroscopy has calcium within few hours of birth. demonstrated increased striatal Generalized convulsions were relieved by myoinositol. An ultrasound of the calcium gluconate whereas hypoxia by abdomen may demonstrate organomegaly, oxygen administration via nasal prongs, signs of cardiomyopathy or valvulopathy bilevel positive airway pressure (BiPAP) may be observed by echocardiography or and oxygen concentrator later in life. electrocardiography and generalized Symptomatic (anticonvulsants for dysrhythmia and epileptogenic foci seizures) and supportive therapy like electroencephalography. Bone marrow proper nutrition, hydration, maintaining aspiration not recommended as diagnostic clear airway, etc. was provided with care test since of nonspecific large foam cells, [17]. Physical examination discovered Gaucher cells, and ballooned cells have facial and peripheral edema, been reported in bone marrow but are kyphoscoliosis, gingival hypertrophy and typically reported in lower concentrations angiokeratomas (red to blue colour benign than in other lysosomal storage disorders cutaneous lesions of capillaries) on thorax,

Journal of Perinatal, Pediatric and Neonatal Nursing Volume 1 Issue 1

abdomen and upper extremities since birth. nurse plays a vital role in educating She was diagnosed with delayed families of patients with GM1 myelination with unmyelination deep gangliosidosis. Planned adequate physical white matter of corona radiata and centrum activity by occupational or physiotherapy semiovale as expected for this age; wide could reduce skeletal difficulties. spaced frontal horn of bilateral ventricles and mild colpocephaly by MRI at 5 DISCUSSION months. At 6 months, the leukocyte GM1 gangliosidoses is an inherited enzyme activity which is measured by beta autosomal recessive disorder with galactosidase (nmol/h/mg) was highly prevalence at birth is approximately diminished (1.2) in comparison to the 1:100,000 to 200,000 live births across the normal range (70-324). USG stated hepato globe [18]. It is due to the marked splenomegaly while visual evoked deficiency of beta – galactosidase resulting potential test revealed sign of visual th in abnormal acidic lipid materials in the pathway dysfunction at 7 month. nerve cells. Generally, GLB1 Piracetam is a gamma amnio butyric acid (galactosidase beta -1) gene help to make a (GABA) analogues (protect brain against vital enzyme called beta – galactosidase shortness of oxygen) was the major and resides in cell compartments (called treatment. Neither bone marrow lysosomes) in order to metabolize certain transplantation (though reported successful molecules like GM1 ganglioside which is in infantile/juvenile for short- term benefit) nor pre-symptomatic cord- blood important for nerve cell function. Any hematopoietic stem-cell transplantation mutation in GLB1 gene may decrease or (recommended due to its success in other eliminate the β -galactosidase enzyme. lysosomal storage disorders) was not done. Consequently, it accumulates to toxic Occupational and Physiotherapy found to levels in tissues and organs, particularly in be beneficial. The child had feeding brain. Therefore, a fatty substance or lipid difficulty and was started on tube feeding. (called GM-1 ganglioside) accumulates She developed abdominal distention, abnormally in the nerve cells. Hence, this severe chest congestion and ended up with accumulation (called substrate) leads to pneumonia. She breathed last on her 10th progressive destruction of nerve cells [3]. birthday. A study was conducted between 2011 and Nursing management 2014 among patients referred from all over Adequate information, support and India and Pakistan. The coarse facies, counselling were made available for parent short stature, multiplex dysostosis (bone to make a future decision which indeed is development disorder, particularly essential. Infant was laid on comfortable ossification), corneal clouding and position and position was changed every hepatosplenomegaly were the most two hourly as the baby could not move by common phenotype considered for her own. The child with infantile type may referred case. The study reported that 4 have feeding problems which could be were diagnosed with GM1 gangliosidosis overcome by tube feeding with adequate by biochemically as well as confirmed by nutrients. Proper neck support, either by DNA analysis [19]. As India is a neck collar or towel, could prevent the developing country, several cases could be complications of atlantoaxial instability. unobserved due to difficulty in Steam inhalation and nebulization interpretation/ unawareness and cost of the followed by chest physiotherapy was investigations. beneficial during chest congestion. A

Journal of Perinatal, Pediatric and Neonatal Nursing Volume 1 Issue 1

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