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Low alkaline phosphatase

MedGen UID:
349734
Concept ID:
C1860130
Finding
Synonym: Decreased serum alkaline phosphatase
 
HPO: HP:0003282

Definition

Abnormally reduced serum levels of alkaline phosphatase. [from HPO]

Conditions with this feature

Cholesteryl ester storage disease
MedGen UID:
40266
Concept ID:
C0008384
Disease or Syndrome
Deficiency of lysosomal acid lipase causes 2 distinct phenotypes in humans: Wolman disease (WOLD; 620151) and cholesteryl ester storage disease (CESD). WOLD is an early-onset fulminant disorder of infancy with massive infiltration of the liver, spleen, and other organs by macrophages filled with cholesteryl esters and triglycerides. Death occurs early in life. CESD is a milder, later-onset disorder with primary hepatic involvement by macrophages engorged with cholesteryl esters. This slowly progressive visceral disease has a wide spectrum of involvement ranging from early onset with severe cirrhosis to later onset of more slowly progressive hepatic disease with survival into adulthood (summary by Du et al., 2001).
Childhood hypophosphatasia
MedGen UID:
65089
Concept ID:
C0220743
Congenital Abnormality
Hypophosphatasia is characterized by defective mineralization of growing or remodeling bone, with or without root-intact tooth loss, in the presence of low activity of serum and bone alkaline phosphatase. Clinical features range from stillbirth without mineralized bone at the severe end to pathologic fractures of the lower extremities in later adulthood at the mild end. While the disease spectrum is a continuum, seven clinical forms of hypophosphatasia are usually recognized based on age at diagnosis and severity of features: Perinatal (severe): characterized by pulmonary insufficiency and hypercalcemia. Perinatal (benign): prenatal skeletal manifestations that slowly resolve into one of the milder forms. Infantile: onset between birth and age six months of clinical features of rickets without elevated serum alkaline phosphatase activity. Severe childhood (juvenile): variable presenting features progressing to rickets. Mild childhood: low bone mineral density for age, increased risk of fracture, and premature loss of primary teeth with intact roots. Adult: characterized by stress fractures and pseudofractures of the lower extremities in middle age, sometimes associated with early loss of adult dentition. Odontohypophosphatasia: characterized by premature exfoliation of primary teeth and/or severe dental caries without skeletal manifestations.
Hereditary acrodermatitis enteropathica
MedGen UID:
66355
Concept ID:
C0221036
Disease or Syndrome
Acrodermatitis enteropathica of the zinc deficiency type (AEZ) is characterized by intermittent simultaneous occurrence of diarrhea and dermatitis with failure to thrive. Alopecia of the scalp, eyebrows, and eyelashes is a usual feature. The skin lesions are bullous. Noteworthy is the cure by diodoquin, or diiodohydroxyquinoline (Dillaha et al., 1953; Bloom and Sobel, 1955). Rodin and Goldman (1969) described autopsy findings, including pancreatic islet hyperplasia, absence of the thymus and of germinal centers, and plasmocytosis of lymph nodes and spleen.
Infantile hypophosphatasia
MedGen UID:
75677
Concept ID:
C0268412
Disease or Syndrome
Hypophosphatasia is characterized by defective mineralization of growing or remodeling bone, with or without root-intact tooth loss, in the presence of low activity of serum and bone alkaline phosphatase. Clinical features range from stillbirth without mineralized bone at the severe end to pathologic fractures of the lower extremities in later adulthood at the mild end. While the disease spectrum is a continuum, seven clinical forms of hypophosphatasia are usually recognized based on age at diagnosis and severity of features: Perinatal (severe): characterized by pulmonary insufficiency and hypercalcemia. Perinatal (benign): prenatal skeletal manifestations that slowly resolve into one of the milder forms. Infantile: onset between birth and age six months of clinical features of rickets without elevated serum alkaline phosphatase activity. Severe childhood (juvenile): variable presenting features progressing to rickets. Mild childhood: low bone mineral density for age, increased risk of fracture, and premature loss of primary teeth with intact roots. Adult: characterized by stress fractures and pseudofractures of the lower extremities in middle age, sometimes associated with early loss of adult dentition. Odontohypophosphatasia: characterized by premature exfoliation of primary teeth and/or severe dental caries without skeletal manifestations.
Adult hypophosphatasia
MedGen UID:
120636
Concept ID:
C0268413
Disease or Syndrome
Hypophosphatasia is characterized by defective mineralization of growing or remodeling bone, with or without root-intact tooth loss, in the presence of low activity of serum and bone alkaline phosphatase. Clinical features range from stillbirth without mineralized bone at the severe end to pathologic fractures of the lower extremities in later adulthood at the mild end. While the disease spectrum is a continuum, seven clinical forms of hypophosphatasia are usually recognized based on age at diagnosis and severity of features: Perinatal (severe): characterized by pulmonary insufficiency and hypercalcemia. Perinatal (benign): prenatal skeletal manifestations that slowly resolve into one of the milder forms. Infantile: onset between birth and age six months of clinical features of rickets without elevated serum alkaline phosphatase activity. Severe childhood (juvenile): variable presenting features progressing to rickets. Mild childhood: low bone mineral density for age, increased risk of fracture, and premature loss of primary teeth with intact roots. Adult: characterized by stress fractures and pseudofractures of the lower extremities in middle age, sometimes associated with early loss of adult dentition. Odontohypophosphatasia: characterized by premature exfoliation of primary teeth and/or severe dental caries without skeletal manifestations.
Glycosylphosphatidylinositol biosynthesis defect 18
MedGen UID:
1648478
Concept ID:
C4748357
Disease or Syndrome
DEE95 is a severe autosomal recessive developmental disorder characterized by severely impaired global development, hypotonia, weakness, ataxia, coarse facial features, and intractable seizures. More variable features may include abnormalities of the hands and feet, inguinal hernia, and feeding difficulties. The disorder is part of a group of similar neurologic disorders resulting from biochemical defects in the glycosylphosphatidylinositol (GPI) biosynthetic pathway (summary by Nguyen et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350. For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures
MedGen UID:
1710849
Concept ID:
C5394372
Disease or Syndrome
Neurodevelopmental disorder with hypotonia and cerebellar atrophy, with or without seizures (NEDHCAS) is an autosomal recessive neurodevelopmental disorder characterized by global developmental delay with variably impaired intellectual development, delayed motor skills, and poor or absent speech. Most patients develop early-onset seizures and demonstrate cerebellar ataxia or dysmetria associated with progressive cerebellar atrophy on brain imaging. The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis (summary by Nguyen et al., 2020). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).
Glycosylphosphatidylinositol biosynthesis defect 25
MedGen UID:
1823964
Concept ID:
C5774191
Disease or Syndrome
Glycosylphosphatidylinositol biosynthesis defect-25 (GPIBD25) is an autosomal recessive neurodevelopmental disorder characterized by global developmental delay, brain anomalies, hypotonia, and contractures (Salian et al., 2022). For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (610293).

Professional guidelines

PubMed

Mornet E, Taillandier A, Domingues C, Dufour A, Benaloun E, Lavaud N, Wallon F, Rousseau N, Charle C, Guberto M, Muti C, Simon-Bouy B
Eur J Hum Genet 2021 Feb;29(2):289-299. Epub 2020 Sep 24 doi: 10.1038/s41431-020-00732-6. PMID: 32973344Free PMC Article
Baujat G, Michot C, Le Quan Sang KH, Cormier-Daire V
Arch Pediatr 2017 May;24(5S2):5S61-5S65. doi: 10.1016/S0929-693X(18)30016-2. PMID: 29405934
Saraff V, Narayanan VK, Lawson AJ, Shaw NJ, Preece MA, Högler W
J Pediatr 2016 May;172:181-186.e1. Epub 2016 Feb 16 doi: 10.1016/j.jpeds.2016.01.045. PMID: 26896157

Recent clinical studies

Etiology

Araci MB, Akgun B, Atik T, Isik E, Ak G, Barutcuoglu B, Ozkinay F
Ann Clin Biochem 2021 Jul;58(4):335-341. Epub 2021 Mar 18 doi: 10.1177/00045632211000102. PMID: 33601892
İnci A, Ergin FBC, Yüce BT, Çiftçi B, Demir E, Buyan N, Okur İ, Biberoğlu G, Öktem RM, Tümer L, Ezgü FS
J Bone Miner Metab 2021 Jul;39(4):598-605. Epub 2021 Jan 6 doi: 10.1007/s00774-020-01193-z. PMID: 33404770
Mornet E, Taillandier A, Domingues C, Dufour A, Benaloun E, Lavaud N, Wallon F, Rousseau N, Charle C, Guberto M, Muti C, Simon-Bouy B
Eur J Hum Genet 2021 Feb;29(2):289-299. Epub 2020 Sep 24 doi: 10.1038/s41431-020-00732-6. PMID: 32973344Free PMC Article
Yang Y, Rader E, Peters-Carr M, Bent RC, Smilowitz JT, Guillemin K, Rader B
BMC Pediatr 2019 Jan 3;19(1):2. doi: 10.1186/s12887-018-1379-1. PMID: 30606146Free PMC Article
Cormier C
Joint Bone Spine 2019 Jul;86(4):459-466. Epub 2018 Oct 6 doi: 10.1016/j.jbspin.2018.10.001. PMID: 30300686

Diagnosis

Mornet E, Taillandier A, Domingues C, Dufour A, Benaloun E, Lavaud N, Wallon F, Rousseau N, Charle C, Guberto M, Muti C, Simon-Bouy B
Eur J Hum Genet 2021 Feb;29(2):289-299. Epub 2020 Sep 24 doi: 10.1038/s41431-020-00732-6. PMID: 32973344Free PMC Article
Cormier C
Joint Bone Spine 2019 Jul;86(4):459-466. Epub 2018 Oct 6 doi: 10.1016/j.jbspin.2018.10.001. PMID: 30300686
Mornet E
Metabolism 2018 May;82:142-155. Epub 2017 Sep 20 doi: 10.1016/j.metabol.2017.08.013. PMID: 28939177
Briot K, Roux C
Arch Pediatr 2017 May;24(5S2):5S71-5S73. doi: 10.1016/S0929-693X(18)30018-6. PMID: 29405936
Rockman-Greenberg C
Pediatr Endocrinol Rev 2013 Jun;10 Suppl 2:380-8. PMID: 23858621

Therapy

Pierpont EI, Simmons JH, Spurlock KJ, Shanley R, Sarafoglou KM
Orphanet J Rare Dis 2021 Feb 12;16(1):80. doi: 10.1186/s13023-021-01722-7. PMID: 33579333Free PMC Article
Hawkes CP, Roy SM, Dekelbab B, Frazier B, Grover M, Haidet J, Listman J, Madsen S, Roan M, Rodd C, Sopher A, Tebben P, Levine MA
J Clin Endocrinol Metab 2021 Jan 23;106(2):e485-e495. doi: 10.1210/clinem/dgaa759. PMID: 33124662Free PMC Article
Genest F, Claußen L, Rak D, Seefried L
Osteoporos Int 2021 Feb;32(2):377-385. Epub 2020 Sep 2 doi: 10.1007/s00198-020-05612-9. PMID: 32879991Free PMC Article
Mori K, Kimura T, Fukuokaya W, Iwatani K, Sakanaka K, Kurokawa G, Yanagisawa T, Sasaki H, Miki J, Shimomura T, Miki K, Hatano T, Endo K, Egawa S
Int J Clin Oncol 2020 Mar;25(3):479-485. Epub 2019 Sep 11 doi: 10.1007/s10147-019-01541-8. PMID: 31512007
Belkhouribchia J, Bravenboer B, Meuwissen M, Velkeniers B
BMJ Case Rep 2016 Jan 28;2016 doi: 10.1136/bcr-2015-212827. PMID: 26823351Free PMC Article

Prognosis

Mori K, Janisch F, Parizi MK, Mostafaei H, Lysenko I, Enikeev DV, Kimura S, Egawa S, Shariat SF
Int J Clin Oncol 2020 Feb;25(2):247-257. Epub 2019 Nov 25 doi: 10.1007/s10147-019-01578-9. PMID: 31768692Free PMC Article
Cormier C
Joint Bone Spine 2019 Jul;86(4):459-466. Epub 2018 Oct 6 doi: 10.1016/j.jbspin.2018.10.001. PMID: 30300686
Briot K, Roux C
Arch Pediatr 2017 May;24(5S2):5S71-5S73. doi: 10.1016/S0929-693X(18)30018-6. PMID: 29405936
Riancho-Zarrabeitia L, García-Unzueta M, Tenorio JA, Gómez-Gerique JA, Ruiz Pérez VL, Heath KE, Lapunzina P, Riancho JA
Eur J Intern Med 2016 Apr;29:40-5. Epub 2016 Jan 11 doi: 10.1016/j.ejim.2015.12.019. PMID: 26783040
Salles JP
Subcell Biochem 2015;76:3-24. doi: 10.1007/978-94-017-7197-9_1. PMID: 26219704

Clinical prediction guides

Santurtún M, Mediavilla-Martinez E, Vega AI, Gallego N, Heath KE, Tenorio JA, Lapunzina P, Riancho-Zarrabeitia L, Riancho JA
Front Endocrinol (Lausanne) 2022;13:965476. Epub 2022 Aug 11 doi: 10.3389/fendo.2022.965476. PMID: 36072928Free PMC Article
Yang Y, Rader E, Peters-Carr M, Bent RC, Smilowitz JT, Guillemin K, Rader B
BMC Pediatr 2019 Jan 3;19(1):2. doi: 10.1186/s12887-018-1379-1. PMID: 30606146Free PMC Article
Mornet E
Metabolism 2018 May;82:142-155. Epub 2017 Sep 20 doi: 10.1016/j.metabol.2017.08.013. PMID: 28939177
Briot K, Roux C
Arch Pediatr 2017 May;24(5S2):5S71-5S73. doi: 10.1016/S0929-693X(18)30018-6. PMID: 29405936
Riancho-Zarrabeitia L, García-Unzueta M, Tenorio JA, Gómez-Gerique JA, Ruiz Pérez VL, Heath KE, Lapunzina P, Riancho JA
Eur J Intern Med 2016 Apr;29:40-5. Epub 2016 Jan 11 doi: 10.1016/j.ejim.2015.12.019. PMID: 26783040

Recent systematic reviews

Mori K, Janisch F, Parizi MK, Mostafaei H, Lysenko I, Enikeev DV, Kimura S, Egawa S, Shariat SF
Int J Clin Oncol 2020 Feb;25(2):247-257. Epub 2019 Nov 25 doi: 10.1007/s10147-019-01578-9. PMID: 31768692Free PMC Article
Bloch-Zupan A
Int J Paediatr Dent 2016 Nov;26(6):426-438. Epub 2016 Mar 31 doi: 10.1111/ipd.12232. PMID: 27030892

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