Clinical and molecular diagnosis of non‐phosphomannomutase 2 N‐linked congenital disorders of glycosylation in Spain

Medrano, Celia; Vega, Ana; Navarrete, Rosa; Ecay, María Jesús; Calvo, Rocío Velasco; Pascual, Samuel Ignacio Pascual; Ruiz-Pons, Mónica; Toledo, Laura; García-Jiménez, Inmaculada; Arroyo, Ignacio; Andrea, Campo; Couce, María L.; Domingo‐Jiménez, M. Rosario; García‐Silva, María Teresa; González‐Gutiérrez‐Solana, Luis; Hierro, Loreto; Martín‐Hernández, Elena; Martínez‐Pardo, Mercedes; Roldán, Susana; Tomas, Miguel Santaularia; Cabrera, José Carlos; MártinezBugallo, F.; Martin-Viota, Lucia; Vitoria-Miñana, Isidro; Lefeber, Dirk; Girós, M.; Serrano, Mercedes; Ugarte, Magdalena; Pérez, Belén; Pérez‐Cerdá, Celia

doi:10.1111/cge.13508

Cited by 33 publications

(32 citation statements)

References 23 publications

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“…Literature review identified 14 articles published from 2005 to 2019 with individuals with ARCL2A or WSS due to deleterious variants in ATP6V0A2 (Medrano et al, 2019: Karacan et al, 2019; Beyens et al, 2019; Kariminejad et al, 2017; Ritelli et al, 2014; Bahena‐Bahena et al, 2014; Gardeitchik et al, 2014; Greally et al, 2014; Fischer et al, 2012; Hucthagowder et al, 2009; Kornak et al, 2008; Mohamed et al, 2011; Morava et al, 2005; Tantcheva‐Poor et al, 2012). A total of 70 affected individuals from 65 families, including ours, were found (Tables S1–S4).…”

Section: Resultsmentioning

confidence: 99%

Review of clinical and molecular variability in autosomal recessive cutis laxa 2A

Morlino

Nardella

Castellana

et al. 2020

American J of Med Genetics Pt A

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ATP6V0A2‐related cutis laxa, also known as autosomal recessive cutis laxa type 2A (ARCL2A), is a subtype of hereditary cutis laxa originally characterized by skin, skeletal, and neurological involvement, and a combined defect of N‐glycosylation and O‐glycosylation. The associated clinical spectrum subsequently expanded to a less severe phenotype dominated by cutaneous involvement. At the moment, ARCL2A was described in a few case reports and series only. An Italian adult woman ARCL2A with a phenotype restricted to skin and the two novel c.3G>C and c.1101dup ATP6V0A2 variants has been reported. A systematic literature review allowed us to identify 69 additional individuals from 64 families. Available data were scrutinized in order to describe the clinical and molecular variability of ARCL2A. About 78.3% of known variants were predicted null alleles, while 11 were missense and 2 affected noncanonical splice sites. Age at ascertainment appeared as the unique phenotypic discriminator with earlier age more commonly associated with facial dysmorphism (p .02), high/cleft palate (p .005), intellectual disability/global developmental delay (p .013), and seizures (p .024). No specific genotype–phenotype correlations were identified. This work confirmed the existence of an attenuated phenotype associated with ATP6V0A2 biallelic variants and offers an updated critique to the clinical and molecular variability of ARCL2A.

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Section: Resultsmentioning

confidence: 99%

Review of clinical and molecular variability in autosomal recessive cutis laxa 2A

Morlino

Nardella

Castellana

et al. 2020

American J of Med Genetics Pt A

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“…For instance, CCDC115-CDG (MIM: #616828) and MPI-CDG (MIM: #602579) have especially severe liver disease [7]. CCDC115-CDG presents with a Wilson disease-like phenotype with hepatosplenomegaly, increased serum aminotransferases, neonatal jaundice, early cirrhosis, and increased liver copper concentration [8][9][10]; other CDG involved with Golgi membrane trafficking such as TMEM199-CDG can also present with similar Wilsonian features [11,12]. MPI-CDG tends to present with severe liver dysfunction and rapidly progressive (sometimes congenital) fibrosis [7,13], although asymptomatic adults have been reported [14,15].…”

Section: Introductionmentioning

confidence: 99%

Liver manifestations in a cohort of 39 patients with congenital disorders of glycosylation: pin-pointing the characteristics of liver injury and proposing recommendations for follow-up

Starosta

Boyer

Tahata

et al. 2021

Orphanet J Rare Dis

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Background The congenital disorders of glycosylation (CDG) are a heterogeneous group of rare metabolic diseases with multi-system involvement. The liver phenotype of CDG varies not only according to the specific disorder, but also from patient to patient. In this study, we sought to identify common patterns of liver injury among patients with a broad spectrum of CDG, and to provide recommendations for follow-up in clinical practice. Methods Patients were enrolled in the Frontiers in Congenital Disorders of Glycosylation natural history study. We analyzed clinical history, molecular genetics, serum markers of liver injury, liver ultrasonography and transient elastography, liver histopathology (when available), and clinical scores of 39 patients with 16 different CDG types (PMM2-CDG, n = 19), with a median age of 7 years (range: 10 months to 65 years). For patients with disorders which are treatable by specific interventions, we have added a description of liver parameters on treatment. Results Our principal findings are (1) there is a clear pattern in the evolution of the hepatocellular injury markers alanine aminotransferase and aspartate aminotransferase according to age, especially in PMM2-CDG patients but also in other CDG-I, and that the cholangiocellular injury marker gamma-glutamyltransferase is not elevated in most patients, pointing to an exclusive hepatocellular origin of injury; (2) there is a dissociation between liver ultrasound and transient elastography regarding signs of liver fibrosis; (3) histopathological findings in liver tissue of PMM2-CDG patients include cytoplasmic glycogen deposits; and (4) most CDG types show more than one type of liver injury. Conclusions Based on these findings, we recommend that all CDG patients have regular systematic, comprehensive screening for liver disease, including physical examination (for hepatomegaly and signs of liver failure), laboratory tests (serum alanine aminotransferase and aspartate aminotransferase), liver ultrasound (for steatosis and liver tumors), and liver elastography (for fibrosis).

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“…At least 38 genetically confirmed patients (from 26 families) have been reported [ 1 – 19 ]. The frequency and the prevalence of the disease are not known.…”

Section: Disease Characteristicsmentioning

confidence: 99%

SRD5A3 defective congenital disorder of glycosylation: clinical utility gene card

2020

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Clinical and molecular diagnosis of non‐phosphomannomutase 2 N‐linked congenital disorders of glycosylation in Spain

Cited by 33 publications

References 23 publications

Review of clinical and molecular variability in autosomal recessive cutis laxa 2A

Review of clinical and molecular variability in autosomal recessive cutis laxa 2A

Liver manifestations in a cohort of 39 patients with congenital disorders of glycosylation: pin-pointing the characteristics of liver injury and proposing recommendations for follow-up

SRD5A3 defective congenital disorder of glycosylation: clinical utility gene card

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