Perinatal lethal hypophosphatasia (PLH) is one of the sub-types of hypophosphatasia. It is one of the most severe types.
The estimated incidence is at ~1:100,000 live births.
This sub type is thought to be due to an ALPL gene mutation location in chromosome 1q36 or the tissue non-specific alkaline phosphatase (TNSALP) gene. It carries an autosomal recessive inheritance. Patients with the heterozygous form of the disease are often normal or may be mildly affected.
- carriers may have low levels of serum alkaline phophatase (ALP)
- fetal ALP isoenzymes are often low on chorionic villus sampling
- urine phosphoethanolamine is elevated
Other features include:
- blue sclerae
- spurs (Bowdler spurs) in the mid-portion of the forearms and lower legs
- marked variability in the amount of bone ossification
- general underossification of the bones of the fetus
- limb shortening
- lack of ossification of groups of vertebral bodies: may sometimes give a pattern of three ossified and three unossified vertebral bodies
- lack of ossification of the neural arches of the spine
- lack of ossification of the hands
- marked demineralisation of the fetal calvarium and absent segments of the spine
- variability between patients as to which bones were most severely affected
- unusually dense, round, flattened, butterfly shaped; and sagittally clefted vertebral bodies
- variability in femoral shape including "chromosome" like, "campomelic" like, and shortening with or without metaphyseal cupping or irregularities
- osteochondral projections of the midshaft of the fibula and ulna
- bifid diaphyses 1
Ancillary antenatal imaging features include
- polyhydramnios on ultrasound
Treatment and prognosis
This sub type is lethal there is no cure. There is a 25% recurrence risk for future pregnancies.
On antenatal ultrasound, it is difficult differentiate type of hypophosphaasia with conditions such as:
achondrogenesis type Ia
- it is the bodies of the spine that are not ossified as opposed to the neural arches in hypophosphatasia
- the calvarium will be ossified in achondrogenesis as opposed to hypophatasia where it will be absent.
osteogenesis imperfecta type II
- in contrast to the thickened bones of osteogenesis type II, the long bones in hypophosphatasia tend to be thin or may be absent.
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