Galactosialidosis in a Newborn with a Novel Mutation in the  CTSA  Gene Presenting with Transient Hyperparathyroidism

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Abstract

Galactosialidosis is a lysosomal storage disease caused by deficiency of protective protein that is encoded by the cathepsin A ( CTSA) gene localized on chromosome 20q13.1. Mutations of this gene are the cause of galactosialidosis that result in loss of function of protective protein. Galactosialidosis is an autosomal recessive inherited disease and has been divided into three subtypes based on age of onset and the severity of clinical manifestations. We report an early infantile form of galactosialidosis in a newborn with a novel mutation on the CTSA gene.

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The natural history and osteodystrophy of mucolipidosis types II and III.

Melanie Alcausin, Michael Fietz, Meredith J.C. Wilson … (2010)

To assess the natural history and impact of the secondary bone disease observed in patients with mucolipidosis (ML) II and III. Affected children and adults were ascertained from clinical genetics units around Australia and New Zealand. Diagnoses were confirmed by the National Referral Laboratory in Adelaide. The study encompassed all patients ascertained between 1975 and 2005. Data focussing on biochemical parameters at diagnosis, and longitudinal radiographic findings were sought for each patient. Where feasible, patients underwent clinical review and examination. Examinations included skeletal survey, bone densitometry, and measurement of serum and urine markers of bone metabolism. In a subset of patients, functional assessment using the Pediatric Evaluation and Disability Inventory (PEDI) and molecular analysis of GNPTAB were performed. Twenty-five patients with mucolipidosis were ascertained over a 30-year period. Morbidity and functional outcomes on living patients were described. Serum calcium and phosphate were normal. All, but one patient, had normal alkaline phosphatase. Serum osteocalcin and urine deoxypyridinoline/creatinine were elevated. Two radiological patterns were observed (i) transient neonatal hyperparathyroidism in infants with ML II and (ii) progressive osteodystrophy in patients with ML intermediate and ML III. Molecular analyses of GNPTAB in nine subjects are reported. ML is characterised by a progressive bone and mineral disorder which we describe as the 'osteodystrophy of mucolipidosis'. The clinical and radiographic features of this osteodystrophy are consistent with a syndrome of 'pseudohyperparathyroidism'. Much of the progressive skeletal and joint pathology is attributable to this bone disorder.

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Clinical utility of whole-exome sequencing in rare diseases: Galactosialidosis.

Carlos E. Prada, Claudia Gonzaga-Jauregui, Rebecca Tannenbaum … (2014)

Rare genetic disorders can go undiagnosed for years as the entire spectrum of phenotypic variation is not well characterized given the reduced number of patients reported in the literature and the low frequency at which these occur. Moreover, the current paradigm for clinical diagnostics defines disease diagnosis by a specified spectrum of phenotypic findings; when such parameters are either missing, or other findings not usually observed are seen, the phenotype driven approach to diagnosis may result in a specific etiological diagnosis not even being considered within the differential diagnosis. The novel implementation of genomic sequencing approaches to investigate rare genetic disorders is allowing not only the discovery of new genes, but also the phenotypic expansion of known Mendelian genetic disorders. Here we report the detailed clinical assessment of a patient with a rare genetic disorder with undefined molecular diagnosis. We applied whole-exome sequencing to this patient and unaffected parents in order to identify the molecular cause of her disorder. We identified compound heterozygous mutations in the CTSA gene, responsible for causing galactosialidosis; the molecular diagnosis was further confirmed by biochemical studies. This report expands on the clinical spectrum of this rare lysosomal disorder and exemplifies how genomic approaches are further elucidating the characterization and understanding of genetic diseases.

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Early-infantile galactosialidosis: prenatal presentation and postnatal follow-up.

Jessica Hellmann, V. Levin, Banappa Unger … (1999)

Galactosialidosis (GS) is an autosomal recessive condition caused by combined deficiency of the lysosomal enzymes beta-galactosidase and alpha-neuraminidase. The combined deficiency has been found to result from a defect in protective protein/cathepsin A (PPCA), an intralysosomal protein which protects these enzymes from premature proteolytic processing. The most severe form of GS, the early-infantile form, results in early onset of edema, ascites, visceromegaly, and skeletal dysplasia. We report a case of early-infantile GS in a male infant who presented with nonimmune fetal hydrops (NIH), "coarse" facial appearance, massive fluid-filled inguinal hernias, multiple telangiectasia, and diffuse hypopigmentation; he subsequently developed visceromegaly. The diagnosis of GS was confirmed biochemically and the defect in PPCA characterized at the protein level. Examination of fetal peripheral blood smears sampled at 30 weeks gestation demonstrated vacuolation of lymphocytes, suggesting blood film examination may be a useful screening tool for cases of NIH where a metabolic disorder is suspected. Skeletal radiography at birth demonstrated punctate epiphyses of the femora, calcanei, and sacrum. We present a discussion of and differential diagnosis for this radiographic finding. To the best of our knowledge, this is the first case of early-infantile GS presenting with stippled epiphyses.

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Journal

Journal ID (nlm-ta): Balkan J Med Genet

Journal ID (publisher-id): bjmg

Journal ID (pmc): bjmg

Title: Balkan Journal of Medical Genetics : BJMG

Publisher: Sciendo

ISSN (Print): 1311-0160

ISSN (Electronic): 2199-5761

Publication date Collection: December 2017

Publication date (Electronic): 29 December 2017

Volume: 20

Issue: 2

Pages: 95-98

Affiliations

[1 ]deptDepartment of Pediatrics, Division of Neonatology , universityAnkara University School of Medicine , Ankara, Turkey

[2 ]deptDepartment of Pediatrics, Division of Pediatric Metabolism , universityAnkara University School of Medicine , Ankara, Turkey

Author notes

[* ] Emel Okulu, M.D., Department of Pediatrics, Division of Neonatology, Ankara University School of Medicine, Tip Fakultesi Street, 06620 Mamak, Ankara, Turkey. Tel: +90-312-595-6599. Fax: +90-312-319-1440. emelokulu@ 123456gmail.com

Article

Publisher ID: bjmg-2017-0031

DOI: 10.1515/bjmg-2017-0031

PMC ID: 5972510

PubMed ID: 29876240

SO-VID: 4d521241-035b-4cd2-aa55-454cd23e3eb3

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This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Galactosialidosis in a Newborn with a Novel Mutation in the CTSA Gene Presenting with Transient Hyperparathyroidism

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Pediatric Pulse: Advancing Neonatal and Child Health

Most cited references 12

The natural history and osteodystrophy of mucolipidosis types II and III.

Clinical utility of whole-exome sequencing in rare diseases: Galactosialidosis.

Early-infantile galactosialidosis: prenatal presentation and postnatal follow-up.

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