Hypophosphatasia

Linglart, Agnès; Duplan, Martin Biosse

doi:10.1007/s11914-016-0309-0

Cited by 98 publications

(83 citation statements)

References 56 publications

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“…1, which shows that in the category of syndromic craniosynostosis with an identified mutation, “other monogenic” (comprising mutations in 20 different genes) is the second leading causal category after FGFR2 mutations in Apert syndrome. These rare diagnoses include potentially treatable conditions for which early recognition is particularly important, such as hypophosphatasia ( ALPL ) [46], Albright osteodystrophy ( GNAS1 ) [47, 48] and rickets ( XLH ) [49]. A diverse variety of chromosomal abnormalities also occurs in association with craniosynostosis, probably often through non-specific mechanisms involving suboptimal brain growth.…”

Section: Molecular Diagnostic Approach To Craniosynostosismentioning

confidence: 99%

Clinical genetics of craniosynostosis

Wilkie

Johnson²,

Wall³

2017

Current Opinion in Pediatrics

145

169

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Purpose of review When providing accurate clinical diagnosis and genetic counselling in craniosynostosis, the challenge is heightened by knowledge that etiology in any individual case may be entirely genetic, entirely environmental, or anything in between. This review will scope out how recent genetic discoveries from next-generation sequencing have impacted on the clinical genetic evaluation of craniosynostosis. Recent findings Survey of a 13-year birth cohort of patients treated at a single craniofacial unit demonstrates that a genetic cause of craniosynostosis can be identified in one quarter of cases. The substantial contributions of mutations in two genes, TCF12 and ERF, is confirmed. Important recent discoveries are mutations of CDC45 and SMO in specific craniosynostosis syndromes, and of SMAD6 in non-syndromic midline synostosis. The added value of exome or whole genome sequencing in the diagnosis of difficult cases is highlighted. Summary Strategies to optimise clinical genetic diagnostic pathways by combining both targeted and next-generation sequencing are discussed. As well as improved genetic counselling, recent discoveries spotlight the important roles of signalling through the bone morphogenetic protein and hedgehog pathways in cranial suture biogenesis, as well as a key requirement for adequate cell division in suture maintenance.

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Section: Molecular Diagnostic Approach To Craniosynostosismentioning

confidence: 99%

Clinical genetics of craniosynostosis

Wilkie

Johnson²,

Wall³

2017

Current Opinion in Pediatrics

145

169

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“…The hypercalcemia is seen in the infantile form of HPP, and may resolve spontaneously within the first year of life, or following targeted asfotase alfa enzyme replacement therapy . However, hypercalcemia may occur in adults with HPP who have been immobilized . In CLD, the severely reduced or absent activity of the gut enzyme lactase, leads to an inability to breakdown dietary lactose, which results in osmotic diarrhea, dehydration, and weight loss shortly after feeding commences, and patients typically have hypercalcemia with nephrocalcinosis.…”

Section: Pth‐independent Hypercalcemiamentioning

confidence: 99%

Hypercalcemic Disorders in Children

Stokes

Nielsen

Hannan

et al. 2017

Journal of Bone and Mineral Research

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Hypercalcemia is defined as a serum calcium concentration that is greater than two standard deviations above the normal mean, which in children may vary with age and sex, reflecting changes in the normal physiology at each developmental stage. Hypercalcemic disorders in children may present with hypotonia, poor feeding, vomiting, constipation, abdominal pain, lethargy, polyuria, dehydration, failure to thrive, and seizures. In severe cases renal failure, pancreatitis and reduced consciousness may also occur and older children and adolescents may present with psychiatric symptoms. The causes of hypercalcemia in children can be classified as parathyroid hormone (PTH)‐dependent or PTH‐independent, and may be congenital or acquired. PTH‐independent hypercalcemia, ie, hypercalcemia associated with a suppressed PTH, is commoner in children than PTH‐dependent hypercalcemia. Acquired causes of PTH‐independent hypercalcemia in children include hypervitaminosis; granulomatous disorders, and endocrinopathies. Congenital syndromes associated with PTH‐independent hypercalcemia include idiopathic infantile hypercalcemia (IIH), William's syndrome, and inborn errors of metabolism. PTH‐dependent hypercalcemia is usually caused by parathyroid tumors, which may give rise to primary hyperparathyroidism (PHPT) or tertiary hyperparathyroidism, which usually arises in association with chronic renal failure and in the treatment of hypophosphatemic rickets. Acquired causes of PTH‐dependent hypercalcemia in neonates include maternal hypocalcemia and extracorporeal membrane oxygenation. PHPT usually occurs as an isolated nonsyndromic and nonhereditary endocrinopathy, but may also occur as a hereditary hypercalcemic disorder such as familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, and familial isolated primary hyperparathyroidism, and less commonly, as part of inherited complex syndromic disorders such as multiple endocrine neoplasia (MEN). Advances in identifying the genetic causes have resulted in increased understanding of the underlying biological pathways and improvements in diagnosis. The management of symptomatic hypercalcemia includes interventions such as fluids, antiresorptive medications, and parathyroid surgery. This article presents a clinical, biochemical, and genetic approach to investigating the causes of pediatric hypercalcemia. © 2017 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.

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“…In patients with HPP, low alkaline phosphatase activity results in the accumulation of phosphorylated substrates, specifically inorganic pyrophosphate, pyridoxal 5′-phosphate and phosphoethanolamine [1, 3–5]. Elevated inorganic pyrophosphate levels inhibit mineralization of the bone matrix, leading to hypomineralization of the skeleton [2, 6–8]. The inability of pyridoxal 5′-phosphate, the circulating form of vitamin B6, to cross the blood-brain barrier likely contributes to the seizures observed in some infants with HPP [2, 8].…”

Section: Introductionmentioning

confidence: 99%

“…Elevated inorganic pyrophosphate levels inhibit mineralization of the bone matrix, leading to hypomineralization of the skeleton [2, 6–8]. The inability of pyridoxal 5′-phosphate, the circulating form of vitamin B6, to cross the blood-brain barrier likely contributes to the seizures observed in some infants with HPP [2, 8]. …”

Section: Introductionmentioning

confidence: 99%

Differential diagnosis of perinatal hypophosphatasia: radiologic perspectives

et al. 2018

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Perinatal hypophosphatasia (HPP) is a rare, potentially life-threatening, inherited, systemic metabolic bone disease that can be difficult to recognize in utero and postnatally. Diagnosis is challenging because of the large number of skeletal dysplasias with overlapping clinical features. This review focuses on the role of fetal and neonatal imaging modalities in the differential diagnosis of perinatal HPP from other skeletal dysplasias (e.g., osteogenesis imperfecta, campomelic dysplasia, achondrogenesis subtypes, hypochondrogenesis, cleidocranial dysplasia). Perinatal HPP is associated with a broad spectrum of imaging findings that are characteristic of but do not occur in all cases of HPP and are not unique to HPP, such as shortening, bowing and angulation of the long bones, and slender, poorly ossified ribs and metaphyseal lucencies. Conversely, absent ossification of whole bones is characteristic of severe lethal HPP and is associated with very few other conditions. Certain features may help distinguish HPP from other skeletal dysplasias, such as sites of angulation of long bones, patterns of hypomineralization, and metaphyseal characteristics. In utero recognition of HPP allows for the assembly and preparation of a multidisciplinary care team before delivery and provides additional time to devise treatment strategies.

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Hypophosphatasia

Cited by 98 publications

References 56 publications

Clinical genetics of craniosynostosis

Clinical genetics of craniosynostosis

Hypercalcemic Disorders in Children

Differential diagnosis of perinatal hypophosphatasia: radiologic perspectives

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