Secondary hemophagocytosis in 3 patients with organic acidemia involving propionate metabolism.

Hemophagocytic lymphohistiocytosis (HLH) may develop secondary to infections, malignancies, immune deficiency syndromes, and rheumatologic and metabolic disorders. Associations between HLH and inborn errors of metabolism, including lysinuric protein intolerance, multiple sulfatase deficiency, galactosemia, Gaucher disease, Pearson syndrome, and galactosialidosis, have previously been reported in the literature. In this report the authors present 3 children with disorders of propionate metabolism--1 with methylmalonic acidemia and 2 with propionic acidemia--who developed secondary HLH during their metabolic attacks. All patients fulfilled the 5 HLH criteria of the Histiocyte Society. Familial HLH was ruled out by molecular analysis. Plasma exchange was performed for 2 of them. Unfortunately 1 died of multiorgan failure despite intensive therapy. This is the first report of such an association.

A Zinc Sulphate-Resistant Acrodermatitis Enteropathica Patient with a Novel Mutation in SLC39A4 Gene.

Acrodermatitis enteropathica (AE) is a rare autosomal recessive disorder of zinc deficiency due to an abnormal intestinal zinc transporter. It is characterized by the triad of acral dermatitis, alopecia, and diarrhoea. Once AE is correctly diagnosed, patients are treated with orally administered zinc sulphate. In some patients, relapses occur during adolescence, despite the regular treatment. Here, we discuss the clinical and molecular features of a 13-year-old adolescent girl with acrodermatitis enteropathica who was resistant to high-dose zinc sulphate therapy. We successfully treated the patient with zinc gluconate and vitamin C, and we detected a novel homozygous c.541_551dup (p.Leu186fsX38) mutation in the exon 3 of her SLC39A4 gene.

Identification of mutations and evaluation of cardiomyopathy in Turkish patients with primary carnitine deficiency.

Primary systemic carnitine deficiency (SCD) is an autosomal recessive disorder caused by defective cellular carnitine transport. Patients usually present with predominant metabolic or cardiac manifestations. SCD is caused by mutations in the organic cation/carnitine transporter OCTN2 (SLC22A5) gene. Mutation analysis of SLC22A5 gene was carried out in eight Turkish patients from six families. Six patients presented with signs and symptoms of heart failure, cardiomyopathy, and low plasma carnitine levels, five of them with concurrent anemia. A patient with dilated cardiomyopathy had also facial dysmorphia, microcephaly, and developmental delay. Tandem MS analyses in siblings of the patients revealed two more cases with low plasma carnitine levels. SCD diagnosis was confirmed in these two cases by mutation screening. These two cases were asymptomatic but echocardiography revealed left ventricular dilatation in one of them. Carnitine treatment was started before the systemic signs and symptoms developed in these patients. Mean value of serum carnitine levels of the patients was 2.63±1.92µmol/L at the time of diagnosis. After 1year of treatment, carnitine values increased to 16.62±5.11 (p<0.001) and all responded to carnitine supplementation clinically. Mutation screening of the OCTN2 gene study in the patients revealed two novel (p.G411V, p.G152R), and four previously identified mutations (p.R254X, p.R282X, p.R289X, p.T337Pfs12X). Early recognition and carnitine supplementation can be lifesaving in this inborn error of fatty acid oxidation.

Does maternal knowledge impact blood phenylalanine concentration in Turkish children with phenylketonuria?

The aim of this study was to compare the level of maternal knowledge and the blood phenylalanine (Phe) control in phenylketonuria (PKU; OMIM 261600). The study was conducted on 144 children (81 boys, 63 girls) with PKU, aged between 1 and 15 years, at Hacettepe University Ihsan Dogramaci Children's Hospital, Metabolism and Nutrition Unit. All subjects were treated with a low-Phe diet using a Phe-exchange system. A 20-question multiple-choice questionnaire was applied to the mothers to determine their knowledge about PKU and its dietary treatment. Questions in the test consisted of the knowledge about the disease (6 questions), general dietary knowledge (14 questions) and knowledge about specific exchange within the dietary questions (6 questions). The median blood Phe concentration for the previous 3-year period was used as an indicator of metabolic control. Eighty-seven children had a median blood Phe concentration above the MRC Working Party Guidelines. There was a negative correlation between maternal knowledge about exchange and median blood Phe concentration in the child (p<0.05). Maternal knowledge about a standard 15 mg Phe exchange system is correlated with dietary compliance as measured by blood Phe concentrations in our subjects. We would like to implement an easier method of measuring Phe exchanges to improve dietary knowledge in the mothers.