A 22-year follow-up reveals a variable disease severity in early-onset facioscapulohumeral dystrophy

Aim

To assess the long-term natural course of early-onset facioscapulohumeral dystrophy (FSHD), which is important for patient management and trial-readiness, and is currently lacking.

The relevance of a geriatric sub-classification of personality disorders in the DSM-V

Little is known about the course of personality disorders across the life span. A major problem is that the current DSM nosology for personality disorders does not account for age-associated changes in behaviour and interpersonal functioning. This editorial will discuss the main diagnostic bottlenecks when applying the current DSM-IV-TR Axis II criteria to older adults. Subsequently, suggestions will be given for future research and the development of a geriatric sub-classification.     

BSCL2 mutations in two Dutch families with overlapping Silver syndrome-distal hereditary motor neuropathy

Mutations in the BSCL2 gene have recently been identified in families with (SPG17-linked) Silver syndrome-type hereditary spastic paraparesis as well as in families with distal hereditary motor neuropathy (HMN). We describe the first two Dutch families with BSCL2 mutations and corroborate the phenotypic variability of this gene mutation, as features compatible with Silver syndrome, variant Silver syndrome (with predominant foot rather than hand muscle involvement), distal HMN type II, or distal HMN type V were all encountered.     

Prevalence of congenital heart defects in neuroblastoma patients: a cohort study and systematic review of literature

Data on the prevalence of congenital heart defects (CHD) in neuroblastoma patients are inconsistent. If CHD are more common in neuroblastoma patients than in the general population, cardiac screening might be warranted. In this study we used echocardiography to determine the prevalence of CHD in a single centre cohort of surviving neuroblastoma patients. In addition, we performed a systematic review of the literature. Echocardiography was performed in 119 of 133 patients (89.5%). Only two patients (1.7%) had CHD. The prevalence of CHD was not significantly different from a previously published control group of 192 leukaemia patients examined by echocardiography (P = 0.49). Literature search revealed 17 studies, showing prevalence rates of CHD in neuroblastoma patients ranging from 0 to 20%. Prevalence was less than 3.6% in the majority of studies. Most studies lacked information on validity. We conclude that current evidence does not support standard cardiac screening in all patients with neuroblastoma.     

Abnormally increased semantic priming in children with symptomatic HIV-1 disease: evidence for impaired development of semantics?

Language deficits are a major characteristic of neurobehavioral dysfunction in pediatric HIV disease. An object decision task, which assessed reaction time facilitation following a semantic or identical prime in comparison to an unrelated prime, was used to investigate whether semantic processing abnormalities could be responsible, in part, for these deficits. Thirty children with vertically acquired HIV infection (M age 9.0 years; range 6-13) participated. Either a picture of the same object (repetition prime), a semantically related object (semantic prime), a semantically unrelated object, or a nonsense object preceded a target picture, which in 50% of the cases was a real object. Brain scans of children were rated and used together with neurobehavioral functioning to classify children as having HIV-related CNS abnormalities (n = 13) or not (n = 17). Increased semantic priming but not repetition priming was associated with a greater degree of cortical atrophy. Furthermore, CNS compromised children had significantly faster reaction times following a semantic prime compared to an unrelated prime than non-compromised patients. This facilitation following semantic priming for the CNS compromised patients (13.3%) almost equaled the facilitation following repetition priming (15.3%) while for the non-compromised patients facilitation following semantic priming (7.9%) was clearly smaller than following repetition priming (14.6%). These data suggest that HIV infection in children may result in a reduced neural network leading to impoverished semantic representations characterized by poor differentiation between closely related objects.     

Different distribution of the genetic subtypes of the Prader�CWilli syndrome in the elderly

The Prader–Willi syndrome (PWS) is a genetic disorder caused by the absent expression of the paternal copy of maternally imprinted genes in chromosome region 15q11–13. The frequencies of different subtypes in PWS are usually given in literature as 70% deletion, 25–30% maternal uniparental disomy (mUPD) and 3–5% others (imprinting centre (IC) defects and translocations). Little is known about factors that influence the frequency of genetic subtypes in PWS. The study sample comprised 102 adults with clinically and genetically confirmed PWS, contacted through the Dutch Prader–Willi Parent Association and through physicians specialized in treating persons with intellectual disabilities. Genetic testing showed 55 persons (54%) with a paternal deletion, 44 persons (43%) with an mUPD and 3 persons (3%) with a defect of the IC. The observed distribution in our study differed from that in literature (70% deletion, 30% mUPD), which was statistically significant (z-score: P<0.05). This was mainly caused by a higher proportion of mUPD in the advanced age groups. Differences in maternal age and BMI of persons with PWS could not explain the differences in distribution across the age groups. Our study population had a much broader age range, compared with other studies, because of a predominance of elderly people (40+ years) with PWS. In other studies, these elderly persons might have been undiagnosed and/or underreported because of a lack of genetic diagnosis. The results underline both the need for correct genetic diagnosis in all persons with PWS and adjustment of the guidelines for preventive management in adulthood.     

Muscle uridine diphosphate-hexosamines do not decrease despite correction of hyperglycemia-induced insulin resistance in type 2 diabetes

Animal studies suggest that overactivity of the hexosamine pathway, resulting in increased UDP-hexosamines [UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDP-GalNAc)] is an important mechanism by which hyperglycemia causes insulin resistance. This study was performed to test this hypothesis in patients with type 2 diabetes mellitus (DM). Eight obese patients with uncontrolled DM type 2 and severe insulin resistance were treated with iv insulin for 28 +/- 6 d aimed at euglycemia. Before and after iv insulin treatment, insulin sensitivity was measured using a hyperinsulinemic euglycemic clamp, and a muscle biopsy was taken for measurement of UDP-GlcNAc, UDP-GalNAc, UDP-glucose, and UDP-galactose levels. Also, isoelectric focusing patterns of serum transferrin and the urinary excretion of glycosaminoglycans as measures of final products of the hexosamine pathway were examined. After euglycemia, insulin resistance improved, as demonstrated by an increase in the glucose infusion rate during the clamp from 12.7 +/- 5.6 to 22.4 +/- 8.8 micro mol/kg.min (P < 0.0005) and a decrease in insulin requirement from 1.7 +/- 0.9 to 1.1 +/- 0.6 U/kg.d (P < 0.005), whereas metabolic control improved. Surprisingly, both UDP-GlcNAc, from 8.81 +/- 1.21 to 12.31 +/- 2.52 nmol/g tissue (P < 0.005), and UDP-GalNAc concentrations, from 4.49 +/- 0.85 to 5.89 +/- 1.55 nmol/g tissue (P < 0.05) increased. Isoelectric focusing patterns of serum transferrin and excretion of glycosaminoglycans were similar before and after euglycemia. In conclusion, after amelioration of hyperglycemia- induced insulin resistance, UDP-hexosamines increased in skeletal muscle of patients with type 2 DM. These results do not support the hypothesis that accumulation of products of the hexosamine pathway plays a major role in hyperglycemia-induced insulin resistance.