Normal Mid-Gestation Fetal Ultrasonography Cannot Reliably Exclude Severe Perinatal Hypophosphatasia.

Area of Science:

• Medical Genetics
• Skeletal Dysplasias
• Prenatal Diagnosis

Background:

• Hypophosphatasia (HPP) is a rare genetic disorder affecting bone mineralization due to mutations in the ALPL gene, leading to deficient tissue-nonspecific alkaline phosphatase.
• The perinatal form of HPP is the most severe, historically associated with high mortality, but now treatable with enzyme replacement therapy.
• Antenatal diagnosis typically relies on mid-gestation ultrasound identifying skeletal undermineralization, a standard screening in the UK.

Observation:

• This report details two cases of perinatal HPP where mid-gestation ultrasounds failed to detect the condition.
• In one case with a family history, third-trimester ultrasound revealed skeletal abnormalities suggestive of HPP.
• In the second case, diagnosis was only confirmed immediately after birth.

Findings:

• Mid-gestation ultrasonography is not a reliable method for excluding perinatal HPP, even in pregnancies with a history of the condition.
• Normal mid-gestation scans can lead to a false sense of security, delaying diagnosis and treatment.

Implications:

• Serial antenatal ultrasonography or prenatal genetic testing should be considered for pregnancies with a family history of HPP.
• Early and accurate diagnosis is crucial for initiating timely enzyme replacement therapy, improving outcomes for infants with perinatal HPP.
• These findings highlight the limitations of current routine antenatal screening for severe HPP and advocate for enhanced diagnostic strategies in at-risk pregnancies.