Clinical, morphological, and molecular aspects of sialic acid storage disease manifesting in utero

Froissart, Roseline; Cheillan, David; Bouvier, Raymonde; Tourret, Séverine; Bonnet, Véronique; Piraud, Monique; Maire, I.

doi:10.1136/jmg.2004.029744

Cited by 43 publications

(27 citation statements)

References 24 publications

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“…This is essentially in keeping with the reported phenotype of other patients with truncating SLC17A5 mutations, suggesting a poor prognosis in patients lacking residual transporter activity (Reviewed in Froissart et al 2005). From a molecular standpoint, both patients were homozygous for the same SLC17A5 mutation (c.526-2A>G).…”

Section: Discussionsupporting

confidence: 84%

“…Findings seen in a subset of cases include dysostosis multiplex, cardiomegaly, heart failure, and prematurity. A majority of ISSD cases demonstrate fetal hydrops and/or ascites; hence, this can be considered a prenatal-onset condition (Froissart et al 2005). General genotype-phenotype correspondences have been established, and (with exceptions) most Salla disease patients have at least one copy of the common Finnish founder allele, p.Arg39Cys (NM_012434.4:c.115C>T) bearing some residual transporter activity in vitro (Aula et al 2000;Morin et al 2004;Verheijen et al 1999;Wreden et al 2005;Mochel et al 2009).…”

Section: Introductionmentioning

confidence: 99%

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Infantile Sialic Acid Storage Disease: Two Unrelated Inuit Cases Homozygous for a Common Novel SLC17A5 Mutation

et al. 2013

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Infantile sialic acid storage disease (ISSD) is a lysosomal storage disease characterized by accumulation of covalently unlinked (free) sialic acid in multiple tissues. ISSD and Salla disease (a predominantly neurological disorder) are allelic disorders caused by recessive mutations of a lysosomal anionic monosaccharide transporter, SLC17A5. While Salla disease is common in Finland due to a founder-effect mutation (p.Arg39Cys), ISSD is comparatively rare in all populations studied.Here, we describe the clinical and molecular features of two unrelated Canadian Inuit neonates with a virtually identical presentation of ISSD. Both individuals presented antenatally with fetal hydrops, dying shortly following delivery. Urinary free sialic acid excretion was markedly increased in the one case in which urine could be obtained for testing; postmortem examination showed a picture of widespread lysosomal storage in both. Both children were homozygous for a novel splice site mutation (NM_012434: c.526-2A>G) resulting in skipping of exon 4 and an ensuing frameshift. Analysis of a further 129 pan-Arctic Inuit controls demonstrated a heterozygous carrier rate of 1/129 (~0.4 %) in our sample. Interestingly, lysosomal enzyme studies showed an unexplained ninefold increase in neuraminidase activity, with lesser elevations in the activities of several other lysosomal enzymes. Our results raise the possibility of a common founder mutation presenting as hydrops in this population. Furthermore, if confirmed in subsequent cases, the marked induction of neuraminidase activity seen here may prove useful in the clinical diagnosis of ISSD.

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Section: Discussionsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Infantile Sialic Acid Storage Disease: Two Unrelated Inuit Cases Homozygous for a Common Novel SLC17A5 Mutation

et al. 2013

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“…Placental histology can serve as an early diagnostic clue for a number of storage diseases, including GM1 gangliosidosis,20,127 MPS VII,128,129 ISSD,130,131 Gaucher disease,132 galactosialidosis,133 and Fabry disease 134. The presence of highly vacuolated cells or cells demonstrating storage should be followed up with enzymatic testing.…”

Section: Frequent Clinical Manifestations In the Neonatal Periodmentioning

confidence: 99%

Lysosomal Storage Disorders in the Newborn

et al. 2009

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Lysosomal storage disorders are rare inborn errors of metabolism, with a combined incidence of 1 in 1500 to 7000 live births. These relatively rare disorders are seldom considered when evaluating a sick newborn. A significant number of the >50 different lysosomal storage disorders, however, do manifest in the neonatal period and should be part of the differential diagnosis of several perinatal phenotypes. We review the earliest clinical features, diagnostic tests, and treatment options for lysosomal storage disorders that can present in the newborn. Although many of the lysosomal storage disorders are characterized by a range in phenotypes, the focus of this review is on the specific symptoms and clinical findings that present in the perinatal period, including neurologic, respiratory, endocrine, and cardiovascular manifestations, dysmorphic features, hepatosplenomegaly, skin or ocular involvement, and hydrops fetalis/congenital ascites. A greater awareness of these features may help to reduce misdiagnosis and promote the early detection of lysosomal storage disorders. Implementing therapy at the earliest stage possible is crucial for several of the lysosomal storage disorders; hence, an early appreciation of these disorders by physicians who treat newborns is essential. Keywordslysosomal storage disorders; neonatal; hydrops; enzyme deficiency THE LYSOSOMAL STORAGE disorders (LSDs) are rare diseases with a combined incidence of ~1 in 1500 to 7000 live births. 1,2 LSDs result from the inherited deficiency of 1 or more of the many catabolic enzymes that are located within the lysosome. This group of inborn errors of metabolism encompasses >50 different diseases, each characterized by the accumulation of specific substrates. [3][4][5][6] There are many steps necessary for the synthesis and processing of lysosomal enzymes, which makes this system prone to dysfunctions that can result from different mechanisms and at many different steps in the pathway.LSDs classically have not been considered disorders of the newborn. Generally, clinicians are taught that newborns with LSDs appear normal at birth and that the symptoms develop progressively over the first few months of life or even after many years. However, a portion

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“…It has been documented in several other lysosomal storage diseases, either isolated or as part of hydrops fetalis, such as Gaucher disease [Sarfati et al, 2000], Wolman disease [Ben-Haroush et al, 2003], sialic acid storage disease [Froissart et al, 2005], and GM1 gangliosidosis [Sinelli et al, 2005]. In NPC it was initially reported in three patients and was identified first as early as 18 weeks gestation [Maconochie et al, 1989;Manning et al, 1990].…”

Section: Discussionmentioning

confidence: 96%

The clinical spectrum of fetal Niemann–Pick type C

Spiegel

Raas‐Rothschild

Reish

et al. 2009

American J of Med Genetics Pt A

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Niemann-Pick type C (NPC) disease is a lysosomal neurovisceral storage disease. The spectrum of the clinical presentation as well as the severity of the disease and the age of presentation may be highly variable. Fetal presentation is rarely described in the literature. Here, we report on seven new cases of fetal onset NPC of whom two were diagnosed in utero and five postnatally. The fetal clinical presentation, included, in utero splenomegaly (6/7), in utero hepatomegaly (5/7), in utero ascites (4/7), intra uterine growth retardation (IUGR) (2/7), and oligohydramnios (2/7). Placentomegaly was present in two of the three pregnancies examined. Congenital thrombocytopenia (4/4), congenital anemia (2/4), and petechial rash (2/5) were diagnosed immediately after birth. Three patients were born preterm. Pregnancy and postnatal outcome were remarkably poor with one case of intrauterine fetal death, one elective termination of pregnancy, and four patients who died within the first months of life from a rapidly fatal neonatal cholestatic disease. NPC1 gene mutation analysis identified all of the mutant alleles including three novel mutations. Splenomegaly, hepatomegaly, and ascites were the most consistent prenatal ultrasonographic findings of the NPC fetuses. We suggest that once identified these findings, should raise the suspicion of fetal NPC. Our study further expands the antenatal clinical spectrum of NPC and provides clues to its prenatal diagnosis.

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Clinical, morphological, and molecular aspects of sialic acid storage disease manifesting in utero

Cited by 43 publications

References 24 publications

Infantile Sialic Acid Storage Disease: Two Unrelated Inuit Cases Homozygous for a Common Novel SLC17A5 Mutation

Infantile Sialic Acid Storage Disease: Two Unrelated Inuit Cases Homozygous for a Common Novel SLC17A5 Mutation

Lysosomal Storage Disorders in the Newborn

The clinical spectrum of fetal Niemann–Pick type C

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