Long-term outcomes in two adult siblings with Fucosidosis – Diagnostic odyssey and clinical manifestations
Fucosidosis (OMIN# 230000) is a rare lysosomal storage disorder (LSDs) caused by mutations in the FUCA1 gene, leading to alpha-L-fucosidase deficiency; it is inherited as an autosomal recessive trait. Fucosidosis represents a disease spectrum with a wide variety of clinical features, but most affect...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Molecular Genetics and Metabolism Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426923000551 |
| _version_ | 1797526217536045056 |
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| author | Nuria Puente-Ruiz Ian Ellis Marsel Bregu Cliff Chen Heather J. Church Karen L. Tylee Shalini Gladston Richard Hackett Andrew Oldham Surinder Virk Christian Hendriksz Andrew A.M. Morris Simon A. Jones Karolina M. Stepien |
| author_facet | Nuria Puente-Ruiz Ian Ellis Marsel Bregu Cliff Chen Heather J. Church Karen L. Tylee Shalini Gladston Richard Hackett Andrew Oldham Surinder Virk Christian Hendriksz Andrew A.M. Morris Simon A. Jones Karolina M. Stepien |
| author_sort | Nuria Puente-Ruiz |
| collection | DOAJ |
| description | Fucosidosis (OMIN# 230000) is a rare lysosomal storage disorder (LSDs) caused by mutations in the FUCA1 gene, leading to alpha-L-fucosidase deficiency; it is inherited as an autosomal recessive trait. Fucosidosis represents a disease spectrum with a wide variety of clinical features, but most affected patients have slow neurologic deterioration. Many patients die young and the long-term clinical outcomes in adult patients are poorly documented. Here, we report the long-term follow up of two Caucasian siblings, a 31-year-old man and 25-year-old woman.We describe the clinical, biochemical, radiological and genetic findings in two siblings affected by Fucosidosis and the differences between them after 19-years follow up. The dermatological features of the younger sibling have been reported previously by Bharati et al. (2007).Both patients have typical features of Fucosidosis, such as learning difficulties, ataxia, and angiokeratomas with differing severity. Case 1 presents severe ataxia with greater limitation of mobility, multiple dysostoses, angiokeratomas on his limbs, retinal vein enlargement and increased tortuosity in the eye and gastrointestinal symptoms. Biochemical analysis demonstrated a deficiency of alpha-fucosidase in leucocytes. Case 2 has a greater number of angiokeratomas and has suffered three psychotic episodes. The diagnosis of Fucosidosis was confirmed in cultured skin fibroblast at the age of 12 years. Molecular analysis of the FUCA1 gene showed a heterozygous mutation c.998G > A p.(Gly333Asp), with a pathogenic exon 4 deletion in the other allele in both patients.Conclusion. Fucosidosis presents a wide clinical heterogeneity and intrafamilial variability of symptoms. Psychosis and gastrointestinal symptoms have not been reported previously in Fucosidosis. |
| first_indexed | 2024-03-10T09:27:05Z |
| format | Article |
| id | doaj.art-e11c82b46a984ceebcbab2acd067099a |
| institution | Directory Open Access Journal |
| issn | 2214-4269 |
| language | English |
| last_indexed | 2024-03-10T09:27:05Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj.art-e11c82b46a984ceebcbab2acd067099a2023-11-22T04:47:28ZengElsevierMolecular Genetics and Metabolism Reports2214-42692023-12-0137101009Long-term outcomes in two adult siblings with Fucosidosis – Diagnostic odyssey and clinical manifestationsNuria Puente-Ruiz0Ian Ellis1Marsel Bregu2Cliff Chen3Heather J. Church4Karen L. Tylee5Shalini Gladston6Richard Hackett7Andrew Oldham8Surinder Virk9Christian Hendriksz10Andrew A.M. Morris11Simon A. Jones12Karolina M. Stepien13Adult Inherited Metabolic Diseases, Salford Royal NHS Foundation Trust, UK; Department of Clinical Medicine, Marqués de Valdecilla University Hospital, López-Albo Post Residency Program, Santander, SpainClinical Genetics, Royal Liverpool Children Hospital, Alder Hey, Liverpool, UKOphthalmology Department, Warrington Hospital, Warrington, UKClinical Neuropsychology Department, Salford Royal Hospital NHS Foundation Trust, Salford, UKWillink Metabolic Unit, St Mary's Hospital, Manchester Foundation Trust, Manchester, UKWillink Metabolic Unit, St Mary's Hospital, Manchester Foundation Trust, Manchester, UKWarrington Primary Care Psychiatry, Warrington, UKNeurology Department, Salford Royal Hospital NHS Foundation Trust, Salford, UKAdult Inherited Metabolic Diseases, Salford Royal NHS Foundation Trust, UKCardiology Department, Warrington Hospital, Warrington, UKUniversity of Pretoria, Steve Biko Academic Unit, Department of Paediatrics, Pretoria, South AfricaWillink Metabolic Unit, St Mary's Hospital, Manchester Foundation Trust, Manchester, UKWillink Metabolic Unit, St Mary's Hospital, Manchester Foundation Trust, Manchester, UKAdult Inherited Metabolic Diseases, Salford Royal NHS Foundation Trust, UK; Division of Cardiovascular Sciences, University of Manchester, Manchester M13 9PL, UK; Corresponding author at: Adult Inherited Metabolic Diseases, Salford Royal NHS Foundation Trust, UK.Fucosidosis (OMIN# 230000) is a rare lysosomal storage disorder (LSDs) caused by mutations in the FUCA1 gene, leading to alpha-L-fucosidase deficiency; it is inherited as an autosomal recessive trait. Fucosidosis represents a disease spectrum with a wide variety of clinical features, but most affected patients have slow neurologic deterioration. Many patients die young and the long-term clinical outcomes in adult patients are poorly documented. Here, we report the long-term follow up of two Caucasian siblings, a 31-year-old man and 25-year-old woman.We describe the clinical, biochemical, radiological and genetic findings in two siblings affected by Fucosidosis and the differences between them after 19-years follow up. The dermatological features of the younger sibling have been reported previously by Bharati et al. (2007).Both patients have typical features of Fucosidosis, such as learning difficulties, ataxia, and angiokeratomas with differing severity. Case 1 presents severe ataxia with greater limitation of mobility, multiple dysostoses, angiokeratomas on his limbs, retinal vein enlargement and increased tortuosity in the eye and gastrointestinal symptoms. Biochemical analysis demonstrated a deficiency of alpha-fucosidase in leucocytes. Case 2 has a greater number of angiokeratomas and has suffered three psychotic episodes. The diagnosis of Fucosidosis was confirmed in cultured skin fibroblast at the age of 12 years. Molecular analysis of the FUCA1 gene showed a heterozygous mutation c.998G > A p.(Gly333Asp), with a pathogenic exon 4 deletion in the other allele in both patients.Conclusion. Fucosidosis presents a wide clinical heterogeneity and intrafamilial variability of symptoms. Psychosis and gastrointestinal symptoms have not been reported previously in Fucosidosis.http://www.sciencedirect.com/science/article/pii/S2214426923000551FucosidosisAngiokeratomasLearning disabilityLong-term outcomesNatural history |
| spellingShingle | Nuria Puente-Ruiz Ian Ellis Marsel Bregu Cliff Chen Heather J. Church Karen L. Tylee Shalini Gladston Richard Hackett Andrew Oldham Surinder Virk Christian Hendriksz Andrew A.M. Morris Simon A. Jones Karolina M. Stepien Long-term outcomes in two adult siblings with Fucosidosis – Diagnostic odyssey and clinical manifestations Molecular Genetics and Metabolism Reports Fucosidosis Angiokeratomas Learning disability Long-term outcomes Natural history |
| title | Long-term outcomes in two adult siblings with Fucosidosis – Diagnostic odyssey and clinical manifestations |
| title_full | Long-term outcomes in two adult siblings with Fucosidosis – Diagnostic odyssey and clinical manifestations |
| title_fullStr | Long-term outcomes in two adult siblings with Fucosidosis – Diagnostic odyssey and clinical manifestations |
| title_full_unstemmed | Long-term outcomes in two adult siblings with Fucosidosis – Diagnostic odyssey and clinical manifestations |
| title_short | Long-term outcomes in two adult siblings with Fucosidosis – Diagnostic odyssey and clinical manifestations |
| title_sort | long term outcomes in two adult siblings with fucosidosis diagnostic odyssey and clinical manifestations |
| topic | Fucosidosis Angiokeratomas Learning disability Long-term outcomes Natural history |
| url | http://www.sciencedirect.com/science/article/pii/S2214426923000551 |
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