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Clinical characteristics of perinatal lethal hypophosphatasia: a report of 6 cases

Akari Nakamura-Utsunomiya1, Satoshi Okada, Keiichi Hara

  • 1Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.

Clinical Pediatric Endocrinology : Case Reports and Clinical Investigations : Official Journal of the Japanese Society for Pediatric Endocrinology
|August 9, 2013
PubMed

Insights

Perinatal lethal hypophosphatasia, a severe inherited disorder, causes respiratory failure and convulsions. Vitamin B6 therapy helped manage seizures, but genetic factors alone don't predict lifespan, highlighting the need for genetic counseling.

Area of Science:

  • Genetics
  • Pediatrics
  • Metabolic Disorders

Background:

  • Hypophosphatasia is a rare inherited disorder caused by deficient tissue-nonspecific alkaline phosphatase activity.
  • The perinatal lethal form is the most severe subtype, presenting with respiratory failure, craniosynostosis, bone abnormalities, convulsions, and hypercalcemia.

Purpose of the Study:

  • To report on six cases of the perinatal lethal form of hypophosphatasia.
  • To analyze clinical manifestations, treatment responses, and genetic findings in these patients.
  • To discuss the implications for genetic counseling.

Main Methods:

  • Case series of six patients with perinatal lethal hypophosphatasia.
  • Ultrasonographic examinations for in utero bone abnormalities.
  • Clinical observation of symptoms, mortality, and response to Vitamin B6 therapy.
  • Genetic analysis, including mutation screening for the 1559delT mutation in the Alkaline Phosphatase (ALP) gene.

Main Results:

  • All patients exhibited in utero long bone shortening.
  • Mortality was high, with two deaths at birth and three before age one, primarily due to respiratory failure from hypoplastic lungs.
  • Convulsions occurred in most survivors, with Vitamin B6 therapy reducing their frequency and severity.
  • The 1559delT mutation was identified as a hotspot, with homozygous mutations observed in two patients who presented with differing symptom severity.

Conclusions:

  • The genotype alone does not always predict the lifespan or severity of symptoms in perinatal lethal hypophosphatasia, despite the 1559delT mutation being a significant factor.
  • Vitamin B6 therapy can be beneficial for managing convulsions but does not always eliminate them.
  • These findings underscore the critical importance of genetic counseling for families affected by this severe disorder.

Keywords:
ALPALPLHypophosphatasiaalkaline phosphataseperinatal lethal form

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