Compound heterozygosity of two functional null mutations in the ALPL gene associated with deleterious neurological outcome in an infant with hypophosphatasia

Hofmann, Christine; Liese, Johannes G.; Schwarz, Tobias; Kunzmann, Steffen; Wirbelauer, Johannes; Nowak, Johannes; Hamann, Joanna; Girschick, Hermann; Graser, Stephanie; Dietz, Karl‐Josef; Zeck, Sabine; Jakob, Franz; Mentrup, Birgit

doi:10.1016/j.bone.2013.02.017

Cited by 33 publications

(31 citation statements)

References 44 publications

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“…We summarized several cases of seizures with HPP that have been fully reported (Balasubramaniam et al 2010;Baumgartner-Sigl et al 2007;Bethenod et al 1967;Belachew et al 2013;Demirbilek et al 2012;Hofmann et al 2013;Litmanovitz et al 2002;Nunes et al 2002;Sia et al 1975;Smilari et al 2005;Yamamoto et al 2004). Seizures of HPP usually occur from days after birth.…”

Section: Seizurementioning

confidence: 91%

Neurological Symptoms of Hypophosphatasia

Taketani¹

2015

Subcellular Biochemistry

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Hypophosphatasia (HPP) is a bone metabolic disorder caused by mutations in the liver/bone/kidney alkaline phosphatase gene (ALPL), which encodes tissue-nonspecific alkaline phosphatase (TNAP). This disease is characterized by disrupted bone and tooth mineralization, and reduced serum AP activity. Along with bone and tooth symptoms, many neurological symptoms, seizure, encephalopathy, intracranial hypertension, mental retardation, deafness, and growth hormone deficiency (GHD), are frequently found in HPP patients. Seizure occurs in severe HPP types soon after birth, and responds to pyridoxine, but is an indicator of lethal prognosis. Encephalopathy rarely presents in severe HPP types, but has severe sequelae. Intracranial hypertension complicated in mild HPP types develops after the age of 1 year and sometimes need neurosurgical intervention. Mental retardation, deafness and GHD are more frequently found in Japanese HPP patients. Mental retardation occurs in all HPP types. Deafness in perinatal lethal type is both conductive and sensorineural. GHD develops in all but perinatal lethal type and the diagnosis tends to delay. The pathogenesis of these neural features of HPP might be due to impairment of both vitamin B6 metabolism and central nervous system development by ALPL mutations.

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Section: Seizurementioning

confidence: 91%

Neurological Symptoms of Hypophosphatasia

Taketani¹

2015

Subcellular Biochemistry

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“…However, patients may become refractory to this, and in some cases vitamin B6 is not able to control seizures. [30][31][32] NSAIDs: the presence of hyperprostaglandinism in childhood HP has been described. 26,33,34 In trials not placebo-controlled, an anti-inflammatory treatment using NSAIDs resulted in a significant improvement of physical activity, a reduction in pain-related complaints and normalisation of prostaglandin (PG) levels.…”

Section: Prognosis (Please Describe)mentioning

confidence: 99%

Clinical utility gene card for: Hypophosphatasia – update 2013

et al. 2013

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“…This was confirmed in knockout mice lacking TNAP which died from seizures (Waymire et al 1995). Pyridoxal phosphate in cerebrospinal fluid was above the normal range in three infants with hypophosphatasia (Baumgartner-Sigl et al 2007;Hofmann et al 2013;Belachew et al 2013) supporting the hypothesis that low alkaline phosphatase activity restricted uptake of vitamin B-6 by the brain. Waymire et al (1995) hypothesized that the seizures resulted from decreased concentration of the inhibitory neurotransmitter, gamma-aminobutyrate (GABA).…”

Section: Vitamin B-6 and Seizuresmentioning

confidence: 60%

“…Analysis of cerebrospinal fluid in infants with hypophosphatasia detected reduced 5-hydroxyindoleacetic acid and homovanillic acid in two out of four cases (Balasubramaniam et al 2010;Hofmann et al 2013;Belachew et al 2013). 3-O-methyldopa and 5-hydroxytryptophan were elevated in the only cases where they were measured (Baumgartner-Sigl et al 2007;Balasubramaniam et al 2010).…”

Section: Developmental Effectsmentioning

confidence: 92%

Vitamin B-6 Metabolism and Interactions with TNAP

Coburn

2015

Subcellular Biochemistry

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Compound heterozygosity of two functional null mutations in the ALPL gene associated with deleterious neurological outcome in an infant with hypophosphatasia

Cited by 33 publications

References 44 publications

Neurological Symptoms of Hypophosphatasia

Neurological Symptoms of Hypophosphatasia

Clinical utility gene card for: Hypophosphatasia – update 2013

Vitamin B-6 Metabolism and Interactions with TNAP

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