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Association of Intermediate Osteopetrosis with Poikiloderma

1999; Oxford University Press; Volume: 14; Issue: 5 Linguagem: Inglês

10.1359/jbmr.1999.14.5.834

1523-4681

Silvia Migliaccio, Matteo Luciani, Anna Taranta, Giulio Rossi, Salvatore Minisola, May El Hachem, Cesare Bosman, Lidia De Felice, Renata Boldrini, Alessandro Corsi, P. Bianco, Anna Teti,

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A 10-year-old female patient was diagnosed radiologically with osteopetrosis at the age of 2 months. The patient is the second child of apparently healthy nonconsanguineous parents. Her 12-year-old brother was unaffected. The father's history was negative. The mother's history revealed the presence of two first grade cousins with Wilson's syndrome, and the only brother died from sudden infant death syndrome during sleep at the age of 12 months. Weight and length of the child at birth was normal. The patient was first seen at the age of 2 months for severe staphylococcus sepsis, bronchopneumonia. Clinical work-up revealed severe anemia and neutropenia. X-ray showed pneumonia and a generalized increase in bone density, sclerosis of vertebrae with "bone in bone" appearance (note arrow), mild sclerosis of the skull, funnel-like appearance of the distal ends of femurs and the proximal ends of tibias with characteristics alternating and lucent bands (note arrow), and "bone in bone" aspect in phalanges of hands and feet (note arrow), with a dramatic decrease of medullary cavities (Fig. 1a–1c). On the basis of these findings, the child was diagnosed with osteopetrosis, confirmed by further X-ray during subsequent hospital admissions. Dental eruption was delayed, and at the age of 8 years the patient required surgical intervention for a dental abscess. She had a peculiar triangular face and saddle nose and showed delayed, but harmonic, skeletal maturation. Markers of bone formation (serum total and bone alkaline phosphatase isoenzymes and osteocalcin) were low for her age, while other bone turnover markers and calcitropic hormones (data not shown) were within normal ranges. Bone biopsy showed an obvious osteosclerotic pattern as described elsewhere (Teti et al., submitted). At the age of 6 months, the proband developed erythematous patches accompanied by blistering and diffuse irregular hypo-/hyperpigmentation which eventually evolved into poikiloderma-like skin lesions. Different degrees of cutaneous alterations were noticed: skin appeared glabrous, with extensive atrophy and hypercheratososis of feet, hands, and knee. Thin hair, nail dystrophy, photosensitivity with spontaneous evolving vesicles, and face erythema were remarkable (Fig. 2a–2c). Some of these alterations improved over the years, whereas the poikiloderma persisted. A skin biopsy at the age of 6 years was consistent with the clinical diagnosis of poikiloderma. The osteopetrotic radiological features improved during the subsequent years as shown in 1d–1f. Despite the radiological improvement, densitometric analysis performed at the age of 9 years still revealed high bone mass for age and gender (L1–L4 774 mg/cm2) with a T score of +1.1. The child continued to develop recurrent pneumonia episodes, and peripheral blood analysis confirmed anemia and neutropenia. At the age of 9 years, in August 1996, granulocyte-colony stimulating factor (5 γ/kg of body weight) was given every other day. After 6 months of this therapeutical approach, neutrophil counts significantly improved (July 1996: white cells (×10−3/μl) 2.2, neutrophils (%) 7.6%; February 1997: white cells 4.3, neutrophils 31%; normal values: white cells 4.8–10.8 × 10−3/μl, neutrophils 40.7–74.0%), and infection episodes decreased. This case history is useful to emphasize that, to the best of our knowledge, the patient presented herein is the first in which osteopetrosis is associated with cutaneous anomalies. The skin alterations described in this patient are similar to the poikiloderma present in a rare autosomal recessive disorder called Rothmund–Thompson syndrome.1 The bone defects associated to this syndrome, however, are basically malformative.2 Altered pigmentation of eyes and coat has been described in an animal model, the so-called mi/mi mouse, which carries mutation at the microphthalmia locus and, similar to our patient, shows an intermediate form of osteopetrosis3 characterized by an increase in size and number of osteoclasts. Although the rather nonmalignant clinical course, the decrease of the osteosclerotic pattern, and the normality of bone resorption biochemical markers suggest an intermediate form of disease,4 due to the severe neutropenia, which is a remarkable feature of malignant osteopetrosis,(5) the prognosis is still uncertain. Further work is in progress to elucidate whether the concomitant skin and skeletal alterations represent a new clinical phenotype or a random association. This study was funded by the Telethon grant #E.456. S. Migliaccio is supported by an Eli Lilly grant.