Hypotrichosis simplex (HS) is a rare form of hereditary alopecia characterized by childhood onset of diffuse and progressive scalp and body hair loss. Although research has identified a number of causal genes, genetic etiology in about 50% of HS cases remains unknown. The present report describes the identification via whole-exome sequencing of five different mutations in the gene LSS in three unrelated families with unexplained, potentially autosomal-recessive HS. Affected individuals showed sparse to absent lanugo-like scalp hair, sparse and brittle eyebrows, and sparse eyelashes and body hair. LSS encodes lanosterol synthase (LSS), which is a key enzyme in the cholesterol biosynthetic pathway. This pathway plays an important role in hair follicle biology. After localizing LSS protein expression in the hair shaft and bulb of the hair follicle, the impact of the mutations on keratinocytes was analyzed using immunoblotting and immunofluorescence. Interestingly, wild-type LSS was localized in the endoplasmic reticulum (ER), whereas mutant LSS proteins were localized in part outside of the ER. A plausible hypothesis is that this mislocalization has potential deleterious implications for hair follicle cells. Immunoblotting revealed no differences in the overall level of wild-type and mutant protein. Analyses of blood cholesterol levels revealed no decrease in cholesterol or cholesterol intermediates, thus supporting the previously proposed hypothesis of an alternative cholesterol pathway. The identification of LSS as causal gene for autosomal-recessive HS highlights the importance of the cholesterol pathway in hair follicle biology and may facilitate novel therapeutic approaches for hair loss disorders in general.

Megaloblastic anaemia in infancy is uncommon in western countries. We describe a case of an exclusively breast-fed monozygous twin with severe vitamin B12 deficiency with haematologic and neurologic abnormalities. Treatment with vitamin B12 resulted in a rapid haematological and clinical improvement.

This study concerns the prognostic value of total cord-blood CK-BB activity measured with a new method in preterm infants at risk of PIVH. Twenty-six patients with gestational age less than 36 weeks were studied. The presence of PIVH was proved by either ultrasound scans or autopsy. Total CK-BB values in cord-blood of infants who developed PIVH were significantly higher than those of patients without cerebral bleeding (P less than 0.001).

No abstract