Search

Kasabach-Merritt phenomenon (KMP) is a rare life-threatening vascular condition of infancy. Prognosis factors and long-term follow-up data are lacking. We retrospectively analysed the records of 24 infants (10 females, 14 males) treated for KMP in the Department of Dermatology of Necker-Enfants Malades Hospital, Paris, France, from 1984 to 2012. Mean duration of thrombocytopaenia (2,000-38,000 platelets/mm3, mean 10,500/µl) was 8.8 months (range 3 days-84 months), which correlated with tumour infiltration depth on imaging. D-dimer levels were always elevated, even before KMP onset. Each patient received a mean of 4.8 different treatments (range 1-10). Median follow-up was 6.5 years (range 2 months-22 years). All infants had residual cutaneous lesions, along with inflammatory manifestations (n = 9), elevated D-dimer (n = 5) and orthopaedic sequelae (n = 5). The permanent coagulopathy (elevated D-dimer) even after resolution of KMP suggests the presence of chronic low-grade platelet trapping, with possible sudden worsening, and raises the possibility of prophylactic anti-platelet therapy.

Type I carbohydrate deficient glycoprotein (CDG) syndrome is an inborn hereditary error of metabolism with a broad clinical spectrum. It is characterized by partial N-glycan deficiency of glycoproteins. Skin features may be part of this syndrome in infancy.A male infant failed to thrive, presenting psychomotor retardation, liver disease and multiple biological abnormalities. Very suggestive prominent skin manifestations were noted including abnormal subcutaneous fat with lipoma-like pads on the lower back and buttocks, thickened orange-peel skin on the limbs, thinned proximal knuckles, inverted nipples. Deficient serum transferrin sialylation and phosphomannomutase deficiency were identified confirming type I CDG syndrome.Although inconstantly present, skin manifestations of type I CDG syndrome are very suggestive and may be the inaugural signs of the disease.

We have investigated 8 patients from 7 unrelated families with lamellar ichthyosis (LI) for defects in the keratinocyte transglutaminase (TGK) gene. We have characterized three novel homozygous mutations and a previously reported splice acceptor site mutation. One patient showed a C-to-T change in the binding site for the transcription factor Sp1 within the promoter region. Another patient had a Gly 143-to-Glu mutation in exon 3 and a third patient, affected with a particular form of LI sparing the four limbs, demonstrated a Val382-to-Met mutation within exon 7. These three patients exhibited drastically reduced transglutaminase activity and an absence of detectable TGK polypeptide, as assessed by immunofluorescence and immunoblotting. Northern blot analysis showed that the Sp1 site mutation was associated with profound reduction of TGK transcript levels whereas normal transcript levels were observed for the two missense mutations. We hypothesize that the Sp1 site mutation impairs transcription of the TGK gene, whereas the two missense mutations induce structural changes leading to protein instability. Linkage to TGK was excluded in another family and no evidence for TGK defect was found in 3 other patients. These results further support the involvement of TGK in some patients with LI. They identify a TGK mutation as a cause for non-generalized LI and further delineate the molecular mechanisms underlying TGK deficiency in LI.