Homozygous familial hypobetalipoproteinemia: two novel mutations in the splicing sites of apolipoprotein B gene and review of the literature.

OBJECTIVE: Familial hypobetalipoproteinemia (FHBL) is autosomal codominant disorder of lipoprotein metabolism characterized by low plasma levels of total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5(th) percentile of the distribution in the population. Patients with the clinical diagnosis of homozygous FHBL (Ho-FHBL) are extremely rare and few patients have been characterized at the molecular level. Here we report the medical history and the molecular characterization of one paediatric patient with clinical features of Ho-FHBL. METHODS: A one month old infant with failure to thrive, severe hypocholesterolemia and acanthocytosis was clinically and genetically characterized. Molecular characterization of the proband and her parents was performed by direct sequencing of the APOB gene and functional role of the identified mutations was assessed by the minigene methodology. RESULTS: The proband was found carrying two novel splicing mutations of the APOB gene (c.3696+1G > C and c.3697-1G > A). CHOK1H8 cells expressing minigenes harbouring the mutations showed that these two mutations were associated with the retention of intron 23 and skipping of exon 24, resulting in two truncated apoB fragments of approximate size of 26-28 % of ApoB-100 and the total absence of apoB. CONCLUSION: We describe the first case of Ho-FHBL due to two splicing mutations affecting both the donor and the acceptor splice sites of the same intron of the APOB gene occurring in the same patient. The clinical management of the proband is discussed and a review of the clinical and genetic features of the published Ho-FHBL cases is reported.

Use of hydrolysates in the treatment of cow's milk allergy.

BACKGROUND: Hydrolyzed formulas (HFs) are in general well tolerated by children with cow's milk allergy (CMA), although cases of allergic reactions have been reported and residual allergenicity of HF has been demonstrated OBJECTIVE: To review the most relevant studies of the HFs for residual allergenicity, tolerance, and safety in the past 20 years. DATA SOURCES AND METHODS: MEDLINE searches for the years 1970 to 2001 using the following algorithm (hydrolysate and allergy; food intolerance/allergy; protein hydrolysate). RESULTS: The literature confirmed that although some antigenicity remains, HFs are well tolerated by children with CMA. Rice HF has proven safe when tested by double-blind, placebo-controlled food challenge in a study population of 18 children allergic both to cow's milk (CM) and soy protein. CONCLUSIONS: Absolute avoidance of CM proteins means substitution by soy-, rice-, or amino acid-based formulas. As 8 to 14% of infants allergic to CM react to soy and amino acid-based formulas are expensive, scientific societies recommend the use of formulas based on extensively hydrolyzed CM proteins as first alternatives in children with CMA. Although both soy- and rice-based HFs have now been shown to be safe for these children, further nutritional and clinical studies are needed.