Hypophosphatasia

Aka: Hypophosphatasia, Odontohypophosphatasia

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II. Epidemiology

  1. Severe disease is rare
    1. Prevalance: 1:100,000 to 1:300,000 live births
  2. Adult form (less severe)
    1. Prevalence: 1:3100 to 1:508

III. Pathophysiology

  1. Rare genetic metabolic disorder
    1. Gene defect encoding activity of tissue non-specific Alkaline Phosphatase (TNSALP)
      1. More than 400 mutations identified
      2. Autosomal Recessive or Autosomal Dominant inheritance
    2. TNSALP substrates accumulate
      1. Inorganic pyrophosphate
      2. Pyridoxal-5'-phosphate
  2. Serum and bone Alkaline Phosphatase deficiency
    1. Hypercalcemia
    2. Ethanolamine phosphatemia and phosphaturia
  3. Associated with severe skeletal defects similar to Vitamin D-resistant Rickets
    1. Failed calcification of calvarium
    2. Costochondral junction beading
    3. Rachitic bone changes

IV. Types

  1. Current classification
    1. Severe (recessive inheritance)
      1. Perinatal
      2. Infantile Severe
    2. Moderate (Autosomal Dominant or recessive inheritance)
    3. Mild
  2. Historical Classification
    1. Perinatal
    2. Prenatal benign
    3. Infantile
    4. Childhood
    5. Adult
    6. Odontohypophosphatasia

V. Findings

  1. Lung
    1. Dyspnea
    2. Cyanosis
  2. Gastrointestinal
    1. Vomiting
    2. Constipation
  3. Renal
    1. Renal calcinosis
  4. Growth and Development
    1. Fetal demise (in utero)
    2. Failure to Thrive
  5. Dental (Odontohypophosphatasia)
    1. Premature deciduous teeth loss
    2. Early adult teeth loss
  6. Musculoskeletal
    1. Osteomalacia
    2. Skeletal defects
    3. Recurrent, poorly healing Fractures
    4. Movement Disorders and Muscle Weakness

VI. Labs

  1. Serum Alkaline Phosphatase
    1. Low for age
  2. Tissue non-specific Alkaline Phosphatase (TNSALP) natural substrate increased levels
    1. Pyridoxal 5'-phosphate
    2. Phosphoethanolamine

VII. Imaging

  1. XRay changes
    1. Rickets like bone changes in children
    2. Fractures (old and new)

VIII. Management

  1. Multidisciplinary team management
  2. Dietary Calcium restriction in children
  3. Targeted enzyme replacement therapy

IX. References

  1. Fenn (2021) J Clin Pathol 74(10):635-40 +PMID: 33931563 [PubMed]
  2. Tournis (2021) J Clin Med 10(23):5676 +PMID: 34884378 [PubMed]

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Related Studies

Ontology: Hypophosphatasia (C0020630)

Definition (NCI) A rare, serious metabolic disorder caused by mutations in the gene encoding tissue non-specific alkaline phosphatase (TNSALP) activity. It is characterized by low activity of TNSALP in the serum. The signs and symptoms vary significantly and include death in utero, failure to thrive, premature loss of deciduous teeth, early loss of the adult dentition, hypercalcemia, osteomalacia, skeletal defects, renal stones, and movement disorders.
Definition (MSH) A genetic metabolic disorder resulting from serum and bone alkaline phosphatase deficiency leading to hypercalcemia, ethanolamine phosphatemia, and ethanolamine phosphaturia. Clinical manifestations include severe skeletal defects resembling vitamin D-resistant rickets, failure of the calvarium to calcify, dyspnea, cyanosis, vomiting, constipation, renal calcinosis, failure to thrive, disorders of movement, beading of the costochondral junction, and rachitic bone changes. (From Dorland, 27th ed)
Definition (CSP) genetic metabolic disorder resulting from serum and bone alkaline phosphatase deficiency leading to hypercalcemia, ethanolamine phosphatemia, and ethanolamine phosphaturia; manifestations include severe skeletal defects resembling vitamin D resistant rickets, failure of the calvarium to calcify, dyspnea, cyanosis, vomiting, constipation, renal calcinosis, failure to thrive, disorders of movement, beading of the costochondral junction, and rachitic bone changes.
Concepts Disease or Syndrome (T047)
MSH D007014
ICD10 E83.39
SnomedCT 124431003, 70848009, 190859005, 360792001
English Hypophosphatasias, hypophosphatasia, hypophosphatasia (diagnosis), Hypophosphatasia [Disease/Finding], Alkaline phosphatase deficiency, Deficiency of alkaline phosphatase (disorder), Deficiency of alkaline phosphatase, Hypophosphatasia (disorder), Hypophosphatasia, NOS, Deficiency of alkaline phosphatase (disorder) [Ambiguous], Hypophosphatasia (disorder) [Ambiguous], Hypophosphatasia
Italian Ipofosfatasia, Carenza di fosfatasi alcalina
Japanese 低ホスファターゼ症, ﾃｲﾎｽﾌｧﾀｰｾﾞｼｮｳ
Swedish Hypofosfatasi
Czech hypofosfatázie, Hypofosfatázie
Finnish Hypofosfatasia
Russian FOSFOETANOLAMINURIIA, GIPOFOSFATAZIIA, ГИПОФОСФАТАЗИЯ, ФОСФОЭТАНОЛАМИНУРИЯ
Polish Hipofosfatazja
Hungarian Hypophosphatasia
Norwegian Hypofosfatasi
Spanish deficiencia de FAL, deficiencia de fosfatasa alcalina (concepto no activo), deficiencia de fosfatasa alcalina (trastorno), deficiencia de fosfatasa alcalina, hipofosfatasia (concepto no activo), hipofosfatasia (trastorno), hipofosfatasia, Hipofosfatasia
Portuguese Profilaxia de sintomas menopáusicos, Hipofosfatasia
Dutch hypofosfatasemie, Fosfatasemie, hypo-, Hypofosfatasemie
French Hypophosphatasie, Maladie de Rathburn, Phosphoéthanolaminurie
German Hypophosphatasie
Derived from the NIH UMLS (Unified Medical Language System)

Ontology: ODONTOHYPOPHOSPHATASIA (disorder) (C1840322)

Concepts Disease or Syndrome (T047)
MSH C564146
English ODONTOHYPOPHOSPHATASIA, ODONTOHYPOPHOSPHATASIA (disorder), Odontohypophosphatasia
Derived from the NIH UMLS (Unified Medical Language System)

Related Topics in Bone Disorders

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