engleski

Galactosialidosis : Congenital presentation with transient hyperparathyroidism

Galactosialidosis is an inherited lysosomal storage disease caused by deficiency of lysosomal protective protein/cathepsin A, with consequent combined decreased activity of beta-galactosidase and alpha-neuraminidase. Clinical presentation is very variable and traditionally classified in early infantile, late infantile and juvenile (adult) type. Here, we describe a patient with neonatal presentation of galactosialidosis and transient hyperparathyroidism, a feature which has not been reported previously. The girl was born as the second child of non-consanguinous, healthy parents. The pregnancy was unremarkable up to 35th week of gestation when ultrasound pointed to polyhydramnion and raised suspicion of multiple fractures of the long bones. Delivery was complicated by breech presentation after 37 weeks of gestation. Birth length was 42 cm and weight 2250 g. Clinical abnormalities were: reduced spontaneous activity, muscular hypotonia, coarse face, hypoplastic orbital arches, gingival hypertrophy, high palate, femoral bowing, anal anteposition, pedes equinovari, right arm longer than the left, short proximal long bones, atrial septal defect type 2. During infancy brain imaging indicated diffuse cortical atrophy and diffuse demyelination. Biochemical abnormalities at age of 2 weeks included: vacuolated lymphocytes in peripheral blood and bone marrow, foamy cells in the bone marrow aspirate, elevated alkaline phosphatase (5x), low serum phosphate and magnesium, generalized hyperaminoaciduria. Parathyroid hormone was increased at the age of 3 weeks (7x) and 5 weeks (4.5x) and normalised by the age of 4 months. 1, 25-(OH)2-D3 was also elevated (2x). Cultured skin fibroblasts showed very increased incorporation of radioactive methylamin of 1.64 kBq/mg protein indicating enlarged lysosomal compartment. In fibroblasts beta-galactosidase activity and alpha-neuraminidase activity was reduced to 13% and 16% of normal, respectively. Bone mineral density was grossly reduced (Z-score -4.75 SD). X-ray of the skeleton showed: severe generalized osteoporosis. Long tubular bones are shortened with wide and fuzzy, steep metaphyses. Web-like structure and widening of flat bones. Vertebral bodies are eliptoid with gibbus deformity at the thoracolumbal region. The spinal channel is wide. Punctiform calcifications are present in soft tissues. Shallow acetabulla. No abnormalities of mineral metabolism could be demonstrated in the mother. To our knowledge, parathyroid hormone hypersecretion has not been reported in galactosialidosis. This case suggests hyperparathyroidism may have a role in the pathogenesis of skeletal abnormalities, at least in severe neonatal forms of this disorder. Further investigations are necessary for elucidation of the observed presentation.

alactosialidosis; hyperparathyreoidism

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