Cloaked bones in Mucolipidosis II - A periosteal reaction in newborns

Case 1

On routine, antenatal ultrasound evaluation of a women at 35 weeks gestation showed a fetus with shortening of all the long bones (<5^th percentile) with bowing and fuzzy margins.

1. Femur length: Abdominal circumference – 0.13 (i.e., <0.16) [Figure 1a]

2. Thoracic circumference: Abdominal circumference – 0.75 (should be <0.6 for lethality)

3. Thoracic circumference – <5^th percentile [Figure 1b].

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Figure 1:

Images of Case 1. (a) Antenatal ultrasonogram of fetal femur shows a short, angulated femur with fuzzy margins. However, there is a good posterior acoustic shadowing suggesting normal bone density (in contrast to decreased bone density in Osteogenesis imperfecta). Femur length was <5^th percentile for the gestational age. (b) Antenatal ultrasonogram at the level of thorax shows the thoracic circumference <5^th percentile. (c) Postnatal radiograph of chest shows narrow (Bell-shaped) thorax with thin osteopenic ribs and hypoplastic scapulae. (d) Anteroposterior radiograph of both upper limbs shows short humeri, periosteal cloaking – severe periosteal reaction along all the long bones, fractures in the left ulna and left humerus, distal metaphyseal cupping, and splaying in both the radius and ulna. (e) Lateral radiograph of spine shows convex anterior margin of vertebrae (ovoid vertebrae).

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The above two values (1 and 3) indicate lethality.

The baby was delivered full term. On physical examination, the baby had a fragile skull, narrow thorax, and short angulated limbs.

Postnatal radiographs show

1. Narrow (Bell-shaped) thorax, thin osteopenic ribs, and hypoplastic scapulae [Figure 1c]

2. Short humeri, periosteal cloaking – severe periosteal reaction along all the long bones, fractures in the left ulna and left humerus, and distal metaphyseal cupping and playing in both the radius and ulna [Figure 1d]

3. Convex anterior margin of vertebrae (Ovoid vertebrae) [Figure 1e].

The baby was positive for I-cell screening test which showed decreased activity of the lysosomal enzyme. The absence of this enzyme was, further, confirmed with whole exome sequencing. Due to narrow chest circumference, the baby developed respiratory infection and succumbed after 2 weeks due to its complications. History of death in elder sibling was due to respiratory distress at 7^th day of life, which is suggestive of genetic etiology [Figure 2].

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Figure 2:

Pedigree chart for Case 1, Bold arrow indicates the child in Case 1.

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Case 2

Another infant presented with short angulated limbs with antenatal ultrasound done elsewhere which was suggestive of short and bowed femur. The infantogram [Figure 3] shows the periosteal cloaking (thick periosteal reaction) and short long bones similar to above-mentioned case. This baby as well was positive for I-cell screening test for Mucolipidosis II. Later, the baby developed respiratory infection and was under intensive care unit. Clinical images of both the cases have been shown in Figure 4.

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Figure 3:

Image of Case 2. Postnatal infantogram shows periosteal cloaking (thick periosteal reaction) and short long bones in all limbs.

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Figure 4:

Clinical image of Case 1 and Case 2. (a) Case 1: Angulated left forearm and hyper-flexed left leg. (b) Case 2: Angulated left leg.

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The ultrasound criteria for lethality is:

1. Chest-to-abdominal circumference ratio of <0.6

2. Femur length-to-abdominal circumference ratios of <0.16.^[5]

The early radiographic features seen in Mucolipidosis II^[6] are increased vertebral body height (80%, nonspecific), talocalcaneal stippling (86%), periosteal cloaking (74%), and vertebral body rounding (50%). Other findings included sacrococcygeal sclerosis (54%) and vertebral body sclerosis (13%). Rickets and hyperparathyroidism-like (pseudohyperparathyroidism) changes were also found in 33% of cases. These changes started in the newborn period. There is conversion from these early infantile radiographic features to dysostosis multiplex changes in 41% of cases.

The differential diagnosis for cases with shortened fetal long bones on antenatal ultrasound is a large number of skeletal dysplasias; hence, definitive diagnosis on antenatal ultrasound could not be given; however, the lethality of the dysplasia can be predicted.

However, the differentials for babies born with osteopenic fractures and shortened limbs include-

1. Congenital rickets/neonatal hyperparathyroidism

2. Hypophosphatasia

3. Osteogenesis imperfect

4. Metabolic disease of preterm

5. Mucolipidosis II/I cell disease.

The biochemical parameters for both the cases were within normal limits ([Table 1] for Case 1). Hence, the possibility of congenital rickets and neonatal hyperparathyroidism was ruled out. Both the babies were born at term; hence, the possibility of metabolic disease of newborn was ruled out. Based on the [Table 2], radiographic diagnosis of Mucolipidosis II was made which was later confirmed with genetic workup. Prognosis of most affected children is that they do not survive past early childhood.^[7] There are currently no approved therapies to reverse the effects of Mucolipidosis II. Current approach is managing specific symptoms through targeted therapies.^[8]