Prenatal mucolipidosis type II (I‐cell disease) can present as Pacman dysplasia

Saul, Robert A.; Proud, Virginia K.; Taylor, Henry; Leroy, Jules; Spranger, Jürgen W.

doi:10.1002/ajmg.a.30716

Cited by 25 publications

(20 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several reports have described cases of ML II that expressed skeletal dysplasia prenatally 28,29) . In Lachman's study 29) , the most common disorders associated with fetal skeletal dysplasia were osteogenesis imperfect (18%), thanatophoric dysplasia (14%), campomelic dysplasia Ile1154GlnfsX3) (B).…”

Section: Discussionmentioning

confidence: 99%

A case of mucolipidosis II presenting with prenatal skeletal dysplasia and severe secondary hyperparathyroidism at birth

et al. 2012

View full text Add to dashboard Cite

Mucolipidosis II (ML II) or inclusion cell disease (I-cell disease) is a rarely occurring autosomal recessive lysosomal enzyme-targeting disease. This disease is usually found to occur in individuals aged between 6 and 12 months, with a clinical phenotype resembling that of Hurler syndrome and radiological findings resembling those of dysostosis multiplex. However, we encountered a rare case of an infant with ML II who presented with prenatal skeletal dysplasia and typical clinical features of severe secondary hyperparathyroidism at birth. A female infant was born at 37+1 weeks of gestation with a birth weight of 1,690 g (<3rd percentile). Prenatal ultrasonographic findings revealed intrauterine growth retardation and skeletal dysplasia. At birth, the patient had characteristic features of ML II, and skeletal radiographs revealed dysostosis multiplex, similar to rickets. In addition, the patient had high levels of alkaline phosphatase and parathyroid hormone, consistent with severe secondary neonatal hyperparathyroidism. The activities of β-D-hexosaminidase and α-N-acetylglucosaminidase were moderately decreased in the leukocytes but were 5- to 10-fold higher in the plasma. Examination of a placental biopsy specimen showed foamy vacuolar changes in trophoblasts and syncytiotrophoblasts. The diagnosis of ML II was confirmed via GNPTAB genetic testing, which revealed compound heterozygosity of c.3091C>T (p.Arg1031X) and c.3456_3459dupCAAC (p.Ile1154GlnfsX3), the latter being a novel mutation. The infant was treated with vitamin D supplements but expired because of asphyxia at the age of 2 months.

show abstract

Section: Discussionmentioning

confidence: 99%

A case of mucolipidosis II presenting with prenatal skeletal dysplasia and severe secondary hyperparathyroidism at birth

et al. 2012

View full text Add to dashboard Cite

show abstract

“…40 The main postnatal manifestations of ML II include gradual coarsening of neonatally evident craniofacial features, early cessation of statural growth and neuromotor development, dysostosis multiplex, and major morbidity by hardening of soft connective tissue about the joints and in the cardiac valves. Fatal outcome occurs often before or in early childhood.…”

Section: Phenotypeegenotype Correlationsmentioning

confidence: 99%

Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands

Cathey

Leroy

Wood

et al. 2009

Journal of Medical Genetics

137

163

View full text Add to dashboard Cite

Objectives Mucolipidoses II and III alpha/beta (ML II and ML III) are lysosomal disorders in which the essential mannose-6-phosphate recognition marker is not synthesized onto lysosomal hydrolases and other glycoproteins. The disorders are caused by mutations in GNPTAB, which encodes two of three subunits of the heterohexameric enzyme, N-acetylglucosamine-1-phosphotransferase. Clinical, biochemical, and molecular findings in 61 probands (63 patients) are presented in order to provide a broad perspective of these mucolipidoses. Methods GNPTAB was sequenced in all probands and/or parents. Activity of several lysosomal enzymes was measured in plasma, and GlcNac-1-phosphotransferase was assayed in leukocytes. Thirty-six patients were studied in detail, allowing extensive clinical data to be abstracted. Results ML II correlates with near total absence of phosphotransferase activity resulting from homozygosity or compound heterozygosity for frameshift or nonsense mutations. Craniofacial and orthopedic manifestations are evident at birth, skeletal findings become more obvious within the first year, and growth is severely impaired. Speech, ambulation, and cognitive function are impaired. ML III retains a low level of phosphotransferase activity due to at least one missense or splice site mutation. The phenotype is milder with minimal delays in milestones, the appearance of facial coarsening by early school age, and slowing of growth after age four years. Conclusions Fifty-one pathogenic changes in GNPTAB are presented, including 42 novel mutations. Ample clinical information improves criteria for delineation of ML II and ML III. Phenotype-genotype correlations suggested in more general terms in earlier reports on smaller groups of patients are specified and extended.

show abstract

“…A review of the literature identified a subset of patients with I-cell disease who presented in the neonatal period with features of “metabolic bone disease” rather than with the common signs of dysostosis multiplex that usually develop later in life. This presentation was accompanied by increased serum parathyroid hormone and alkaline phosphatase activity but normal calcium concentrations 36–42…”

Section: Frequent Clinical Manifestations In the Neonatal Periodmentioning

confidence: 99%

Lysosomal Storage Disorders in the Newborn

et al. 2009

View full text Add to dashboard Cite

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

show abstract

Prenatal mucolipidosis type II (I‐cell disease) can present as Pacman dysplasia

Cited by 25 publications

References 15 publications

A case of mucolipidosis II presenting with prenatal skeletal dysplasia and severe secondary hyperparathyroidism at birth

A case of mucolipidosis II presenting with prenatal skeletal dysplasia and severe secondary hyperparathyroidism at birth

Phenotype and genotype in mucolipidoses II and III alpha/beta: a study of 61 probands

Lysosomal Storage Disorders in the Newborn

Contact Info

Product

Resources

About