Case Report: A Novel Synonymous ARPC1B Gene Mutation Causes a Syndrome of Combined Immunodeficiency, Asthma, and Allergy With Significant Intrafamilial Clinical Heterogeneity.

Recently, a novel syndrome of combined immune deficiency, infections, allergy, and inflammation has been attributed to mutations in the gene encoding actin-related protein 2/3 complex subunit 1B (ARPC1B), which is a key molecule driving the dynamics of the cytoskeleton. Homozygous mutations in the ARPC1B gene have been found to result in the disruption of the protein structure and cause an autosomal recessive syndrome of combined immune deficiency, impaired T-cell migration and proliferation, increased levels of immunoglobulin E (IgE) and immunoglobulin A (IgA), and thrombocytopenia. To date, only a few individuals have been diagnosed with the ARPC1B deficiency syndrome worldwide. In this case series, we report the wide spectrum of phenotype in 3 siblings of a consanguineous family from Afghanistan with a novel homozygous synonymous pathogenic variant c.783G>A, p. (Ala261Ala) of the ARPC1B gene that causes a similar syndrome but no thrombocytopenia. Targeted RNA studies demonstrated that the variant affects the splicing process of mRNA, resulting in a marked reduction of the levels of primary (normal) RNA transcript of the ARPC1B gene in the affected patients and likely premature termination from the abnormally spliced mRNA. The next generation sequencing (NGS) studies facilitated the diagnosis of this rare combined immunodeficiency and led to the decision to treat the affected patients with hematopoietic cell transplant (HCT) from an human leukocyte antigen (HLA)-matched healthy sibling.

ROHHAD syndrome - A still unrecognized cause of childhood obesity: report of three cases.

Objectives Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare, potentially fatal, pediatric syndrome. Case presentations We describe three cases of ROHHAD-syndrome in Greece. The main and earliest symptom was the excessive and rapid weight gain at 5, 2, and 3 years of age. Years after the onset of obesity, the patients developed hypothalamic dysfunction with various endocrinological abnormalities (at 9, 8, and 6.8 years, respectively), autonomic dysregulation and finally, alveolar hypoventilation (at 14.6, 8, and 7.8 years, respectively), leading to the diagnosis of ROHHAD-syndrome. Conclusions The rarity of the syndrome, the variable symptoms' presentation, and the lack of specific diagnostic tests could explain why no previous cases have been reported from our country. The rapid onset of obesity was underestimated, and the patients were misdiagnosed with other more common obesity syndromes. Therefore, we propose a questionnaire to help physicians identify patients with ROHHAD-syndrome.

Retrospective analysis of the relationship between infantile seborrheic dermatitis and atopic dermatitis.

A growing number of dermatologists dispute the existence of infantile seborrheic dermatitis (ISD) as an independent clinical entity. Therefore the aim of the present study was to estimate the epidemiologic features of ISD in a defined population of Greek children, assess its course, and identify associations, if any, with other common dermatoses of childhood. Children from the region of Athens who were examined and diagnosed with typical clinical features of ISD between 1997 and 2011 were included in the study. The relevant data were collected retrospectively from their medical records using a standardized form. Eighty-seven children were enrolled (50 boys, 37 girls; mean age 3.1 mos at the time of ISD diagnosis). The main body areas affected were the scalp and face for the majority of the children (78/87), whereas the trunk and limbs were less frequently involved (9/87). In all cases, erythema and scaling of affected patients were mild to moderate. Forty-nine of the 87 children were followed up over a period of 5 years. Thirty children in this group developed features of atopic dermatitis (AD) at a later stage, according to the UK diagnostic criteria of AD, and 23 of these children were diagnosed with AD, at an average time interval of 6.4 months from ISD onset, and seven presented with clinical features of AD at the time of ISD diagnosis. The remaining 19 children in the follow-up group progressed without developing any other chronic skin disease, and all recovered within 6 months of its onset. Thirty-eight had no further follow-up after their initial ISD diagnosis. In spite of the lack of information on the disease course for the last group, assuming they all recovered, the prevalence of AD (34.4%) in our ISD sample was significantly higher than the prevalence of AD (10.7%) in the general population for the same age group, as shown in a previous study performed in the municipality of Athens (p < 0.001). A significant number of children were found to develop AD shortly after their ISD diagnosis. This finding demonstrates a strong association in the clinical course between the two diseases or indicates that the two diseases may be in the same clinical spectrum. Further epidemiologic studies must be conducted to assess the significance of this finding.

Levodopa-induced dyskinesias in tyrosine hydroxylase deficiency.

The objective of this study was to characterize levodopa (l-dopa)-induced dyskinesias in patients with tyrosine hydroxylase deficiency. Clinical observation was carried out on 6 patients who were diagnosed with tyrosine hydroxylase deficiency and were treated with escalating doses of l-dopa. All 6 patients showed l-dopa-induced dyskinesias of variable intensity early in the course of treatment and regardless of the age of initiation. l-Dopa-induced dyskinesias were precipitated by increases in the dose of l-dopa and also by febrile illnesses and stress. They caused dysfunction and distress in 2 patients. The dyskinesias were improved by decreasing the l-dopa dose or by slowing its titration upward. Increasing the dose frequency was helpful in 2 patients, and introducing amantadine was helpful in another 2 patients. l-Dopa-induced dyskinesias are a common phenomenon in tyrosine hydroxylase deficiency. The current observations show that l-dopa-induced dyskinesias are frequent in a dopamine-deficient state in the absence of nigrostriatal degeneration. Although l-dopa-induced dyskinesias in tyrosine hydroxylase deficiency are phenomenologically similar to those that occur in Parkinson's disease, they are different in a number of other respects, suggesting intrinsic differences in the pathophysiologic basis of l-dopa-induced dyskinesias in the 2 conditions. © 2013 Movement Disorder Society.

Chylomicron retention disease: report of two cases from a Greek Island.

Chylomicron retention disease (CRD), or Anderson disease, is a rare, hereditary cause of fat malabsorption. It is one of the familial hypocholesterolaemia syndromes, along with homozygous hypobetalipoproteinaemia (HBL) and abetalipoproteinaemia (ABL). We report clinical, laboratory and histological data as well as molecular DNA analysis in the case of a 4-month-old boy with failure to thrive and steatorrhea who was diagnosed with CRD. His mother's first cousin, who was diagnosed as hypobetalipoproteinaemia 30 years ago, was also reviewed and his diagnosis was revised to CRD. Both patients were treated with a low fat diet and supplementation with fat-soluble vitamins resulting in significant improvement. In conclusion, CRD is a well-defined cause of fat malabsorption and can be distinguished from other forms of familial hypocholesterolaemia because of its specific lipid profile.

Tyrosine hydroxylase deficiency in three Greek patients with a common ancestral mutation.

We present the clinical, biochemical, and molecular findings of three Greek patients with tyrosine hydroxylase (TH) deficiency. All patients presented with a severe clinical phenotype characterized by prominent motor delay, infantile parkinsonism, oculogyric crises, and signs of autonomic dysfunction. Cerebrospinal fluid analysis disclosed reduced dopamine metabolites and normal pterins. Response to levodopa was favorable though not dramatic. All patients were homozygous for a previously reported mutation (p.L236P). SNP haplotype analysis was consistent with a common ancestral mutation, thus indicating a founder effect in Greek patients with TH deficiency.

A male with polysyndactyly, linear skin defects and sclerocornea. Goltz syndrome versus MIDAS.

Focal dermal hypoplasia (FDH) or Goltz syndrome is a rare clinical syndrome presenting with cutaneous, skeletal, dental, ocular, central nervous system and soft-tissue defects. We report on a male infant with characteristic skin defects of the face, trunk and extremities, polysyndactyly and unusual ocular and brain findings. He had sclerocornea of the right eye, anterior persistent hyperplastic primary vitreous of the left eye and hydrocephalus. Clinical findings support the diagnosis of Goltz syndrome. The clinical picture of Goltz syndrome is compared with that of MIDAS syndrome.