Do Not Miss the (Genetic) Diagnosis of Gaucher Syndrome: A Narrative Review on Diagnostic Clues and Management in Severe Prenatal and Perinatal-Lethal Sporadic Cases

Jezela‐Stanek, Aleksandra; Kleinotienė, Gražina; Chwiałkowska, Karolina; Tylki‐Szymańska, Anna

doi:10.3390/jcm10214890

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…GD type 2 (# 230900) has been termed as acutely neuronopathic because of progressive neurodegeneration, while GD type 3 (# 231000), a subacute neuronopathic form, has a later onset of CNS signs and a highly variable rate of progression. Opisthotonus, bulbar signs (swallowing disorders), oculomotor paralysis (or bilateral fixed strabismus), and hepatosplenomegaly in the first 3–6 months of a patient’s life are very suggestive of GD type 2 [ 19 ]. GD3 patients usually present with similar somatic signs and symptoms to those observed in GD1 [ 20 , 21 ].…”

Section: The Liver and Gaucher Disease Acid Sphingomyelinase Deficien...mentioning

confidence: 99%

The Liver and Lysosomal Storage Diseases: From Pathophysiology to Clinical Presentation, Diagnostics, and Treatment

Lipiński,

Tylki-Szymańska

2024

Diagnostics

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The liver, given its role as the central metabolic organ, is involved in many inherited metabolic disorders, including lysosomal storage diseases (LSDs). The aim of this manuscript was to provide a comprehensive overview on liver involvement in LSDs, focusing on clinical manifestation and its pathomechanisms. Gaucher disease, acid sphingomyelinase deficiency, and lysosomal acid lipase deficiency were thoroughly reviewed, with hepatic manifestation being a dominant clinical phenotype. The natural history of liver disease in the above-mentioned lysosomal disorders was delineated. The importance of Niemann–Pick type C disease as a cause of cholestatic jaundice, preceding neurological manifestation, was also highlighted. Diagnostic methods and current therapeutic management of LSDs were also discussed in the context of liver involvement.

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Section: The Liver and Gaucher Disease Acid Sphingomyelinase Deficien...mentioning

confidence: 99%

The Liver and Lysosomal Storage Diseases: From Pathophysiology to Clinical Presentation, Diagnostics, and Treatment

Lipiński,

Tylki-Szymańska

2024

Diagnostics

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“…24,26,28,33 In others, these were histological findings (GBA, IMPAD1, and EPG5) or dissection findings (cerebral hemisphere fusion in POMT1, CENPJ, and NBN), which are often not available in postnatal cohorts. 20,21,23,32,[35][36][37] In certain instances, these unusual findings appear to be consequences of a more severe genotype, for example, nonsense CDK8 variant presenting with lethality, biallelic variants in dominant disorder genes presenting with severe manifestations (ENG) or digenic inheritance with blended phenotype (FBN1&FBN2 variant co-inheritance). Genotype-phenotype studies in other genetic diseases have revealed similar correlations of complex phenotypes with severe genotypes.…”

Section: T a B L E 1 Cases With Variants In Same Molecular Pathways O...mentioning

confidence: 99%

Fetal phenotypes of Mendelian disorders: A descriptive study from India

et al. 2022

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Objective: Exome sequencing (ES)-based diagnosis of Mendelian diseases in the fetus is limited by paucity of phenotypic information. This study reports the comprehensive phenotypes of some fetuses with Mendelian disorders. Methods: Next generation technology-based sequencing of all coding regions of the genome (Exome sequencing) or targeted gene sequencing using Sanger or next generation platforms was performed in a cohort of deeply phenotyped, cytogenetically normal fetuses with morphological defects. Prenatal ultrasonographic phenotypes and postmortem details including dysmorphology, histopathology, and radiography were ascertained. Novel candidate genes, novel/unusual findings, and unusual genotypes in cases with confirmed Mendelian disorders are described. Results: Of the 102 fetuses sequenced, 45 (44%) achieved definitive diagnosis of aMendelian disorder with 50 pathogenic/likely pathogenic variants. The majority (87%) were autosomal recessive, 69% families were consanguineous, and 54% variants were novel. Dysmorphic syndromes, skeletal dysplasias, and metabolic disorders were the commonest disease categories, ciliopathies and dystroglycanopathies, commonest molecular categories. We describe the first fetal description of six monogenic diseases, and nine cases with novel histological findings. Nineteen cases had novel/unusual findings. Conclusion:This cohort demonstrates how deep fetal phenotypes of some Mendelian disorders can show novel/unusual findings, which have important implications for prenatal diagnosis of these conditions. Key pointsWhat's already known about this topic � Exome sequencing improves the genetic diagnostic yield in fetuses with abnormal perinatal phenotypes.� Knowledge of perinatal phenotypes of Mendelian disorders is limited and this compromises use of exome sequencing in prenatal period.� Dysmorphology plays an important role in recognition of Mendelian disorders.Neelam Saini and Vijaya Sree Venkatapuram have contributed equally

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Neuronopathic Gaucher disease: Rare in the West, common in the East

Goker‐Alpan,

Ivanova

2024

J of Inher Metab Disea

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Gaucher disease (GD) stands as one of the most prevalent lysosomal disorders, yet neuronopathic GD (nGD) is an uncommon subset characterized by a wide array of clinical manifestations that complicate diagnosis, particularly when neurological symptoms are understated. nGD may manifest as the acute neuronopathic type, or GD type 2 (GD2), either prenatally or within the first weeks to months of life, whereas GD type 3 (GD3) symptoms may emerge at any point during childhood or occasionally in adolescence. The clinical presentation encompasses severe systemic involvement to mild visceral disease, often coupled with a spectrum of progressive neurological signs and symptoms such as cognitive impairment, ataxia, seizures, myoclonus, varying degrees of brainstem dysfunction presenting with stridor, apneic episodes, and/or impaired swallowing. This manuscript aims to provide a comprehensive review of the incidence, distinctive presentations, and diverse clinical phenotypes of nGD across various countries and regions. It will explore the natural history of the neurodegenerative process in GD, shedding light on its various manifestations during infancy and childhood, and offer insights into the diagnostic journey, the challenges faced in the clinical management, and current and investigative therapeutic approaches for GD's neurological variants.

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Do Not Miss the (Genetic) Diagnosis of Gaucher Syndrome: A Narrative Review on Diagnostic Clues and Management in Severe Prenatal and Perinatal-Lethal Sporadic Cases

Cited by 4 publications

References 26 publications

The Liver and Lysosomal Storage Diseases: From Pathophysiology to Clinical Presentation, Diagnostics, and Treatment

The Liver and Lysosomal Storage Diseases: From Pathophysiology to Clinical Presentation, Diagnostics, and Treatment

Fetal phenotypes of Mendelian disorders: A descriptive study from India

Neuronopathic Gaucher disease: Rare in the West, common in the East

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