A Novel Pathological ARSB Mutation (c.870G>A; p.Trp290stop) in Mucopolysaccharidosis Type VI Patients.

Mucopolysaccharidosis (MPS) type VI, also known as Maroteaux-Lamy syndrome, is a lysosomal storage disorder, characterized by the deficiency of the arylsulfatase B enzyme. The clinical phenotype and severity of the illness varies according to the residual enzyme activity. Typical features are a short stature, shortened trunk, protuberant abdomen, flexed-knee stance, arched back, corneal clouding, joint stiffness and contractures as well as a waddling gait. Patients typically have Hurler-like dysmorphic facial features: microcephaly, prominent forehead and eyes, a broad nose, low nasal bridge, thick lips, and hyperplastic gums with widely spaced teeth. Complications of the illness include obstructive airway, cardiac valvular problems, splenomegaly, hernias, and pneumonia. Unlike other MPS diseases, MPS VI is characterized by normal intellectual development. Since the disease is due to deficient glycosaminoglycan (mucopolysaccharide) metabolism, elevated urinary glycosaminoglycan levels are a main indicator of MPS. Diagnosis is confirmed by enzyme assays, specifically low arylsulfatase B activity in conjunction with the normal activity of other lysosomal enzymes. Enzyme replacement therapy and hematopoietic stem cell therapy are showing positive results in the management of the condition. The more severely affected patients, with a rapidly advancing form of the disease, have a short life span and succumb, most commonly to heart failure, by early adulthood. The frequency of ARSB variants in patients with MPS VI are as follows: 59.5% missense, 13.5% small deletions, 12% nonsense, 5% splice site or intronic variants, 3% small duplications, 3% large deletions, and 1% stop-loss. We report an Albanian family with siblings diagnosed with MPS Vl after clinical examination, biochemical tests, and molecular analysis. Hereby, a novel c.870G>A nonsense homozygous mutation was found responsible for the loss of the enzyme activity.

Genetic Diagnosis of Chromosomal Congenital Anomalies in Albanian Pediatric Patients by Array CGH.

AIM: The aim of our study was to identify chromosomal imbalances by whole-genome microarray-based comparative genomic hybridization (array CGH) in DNA samples of children in which karyotype results cannot be obtained. The present paper describes the first Albanian experience of an array CGH application. MATERIAL AND METHODS: The cohort included seven children with developmental delay or intellectual disability, facial dysmorphism and congenital anomalies according to clinical criteria, suggestive of chromosomal anomalies. The age range was from newborn to five years old. The cytogenetic analysis determined by a standard method of G-banding according to the International System for Human Cytogenetic Nomenclature (ISCN 2005) was performed for all our patients, while array CGH was performed on genomic DNA isolated from the blood of 7 cases. RESULTS: Among the seven patients analysed with array CGH, three patients resulted in duplication and one deletion, one patient with a microdeletion and three patients with duplication. Array CGH facilitated the recognition of submicroscopic deletions and duplications as risk factors for genetic diagnosis in all our patients. CONCLUSIONS: Our case series with congenital chromosomal anomalies confirms the high diagnostic value of the method, as suggested by previous studies. The technique must be available also in less developed countries, to significantly improve the genetic diagnosis of paediatric patients with developmental delay or intellectual disability, congenital anomalies and dysmorphic features. The identification of chromosomal abnormalities in these patients and the genetic counselling will provide family members with an explanation for their child's developmental disability or birth defect, allowing better information about recurrence risks, and permit the anticipation of certain medical problems that require intervention.

Turner syndrome in Albania and the efficacy of its treatment with growth hormone.

The aim of this study was the evaluation of Turner syndrome inside the Albanian population, its clinical, cytological and genetic characteristics, the accompanying pathologies, and the efficacy of the treatment with the growth hormone. We performed a retrospective analysis of 59 patients suffering from this syndrome (aging from 5 to 23 years old). The diagnosis of female patients suffering from Turner syndrome is delayed, with a mean age at the moment of diagnosis of 13.74 years (5-23 years). The main reason for seeking medical advice was the growth retardation or a delayed puberty. Available data for 52 patients showed that the most frequent accompanying pathologies were the following: thyroid autoimmune disorders (59%), cardiovascular anomalies (43%), renal pathologies (41%), hearing impairment (4.3%) and hypertension (3.3%). Follow-up for the growth rate was possible for 52 patients out of the total of 59 patients. Twenty-five of the female patients suffering Turner syndrome and forming part of our study sample were treated with growth hormone for a period averaging 3 years and 4 months. A variety of reasons was identified as responsible for the missed treatment in 27 patients. We saw an enhanced growth (in terms of body height) within the treated subgroup, when compared with the untreated subgroup (27 patients), especially during the first 3 years of the follow-up. No side effects of this treatment were reported. Both groups of patients initiated as well a sexual hormone therapy (estrogens and progesterone) for inducing puberty at the age of 12 years. Further work is needed for an early diagnosis of this syndrome, the prompt treatment with growth hormone and the monitoring of accompanying disorders. This will ensure a better quality of life and an improvement of the longevity of patients suffering from the Turner syndrome.

Pompe disease with heterogeneous presentations within a family.

Pompe disease is an acid maltase deficiency being part of glycogen storage diseases that affects all age groups. In both childhood and adult forms, the classic clinical picture is that of a progressive myopathy. Respiratory muscle involvement is common, may occur early in the course of the disease, and is the most frequent cause of mortality from acid maltase deficiency. Its association with rhabdomyolysis is rare and with a fatal prognosis. We describe the cases of a family with Pompe disease with a clinical spectrum extending throughout different ages of onset, degrees of organ involvement, and rates of progression. The twin patients with adult form of Pompe disease presented episodes of acute renal failure and respiratory insufficiency with a good outcome.

A pilot beta-thalassaemia screening program in the Albanian population for a health planning program.

In Albania, no definite national screening programme of beta-thalassaemia has yet been developed for carrier detection. Only limited information about the occurrence and the types of haemoglobin abnormalities is available. Thus, an educational and screening programme was carried out in one high school with a total of 217 young students from the coastal province of Lushnja in Albania. The pilot programme included a systematic sampling of whole saliva, DNA genomic extraction and the determination of defective beta-thalassaemia genes by reverse dot-blot hybridization with 22 probes specific for the Mediterranean populations.Of the 201 subjects tested, 17 (8.4%) students turned out to be carriers of beta-thalassaemia mutations and haemoglobin variants. The most common mutation is HbS (c.20A-->T) with a frequency of 3.2%, followed by IVS-I-110 (G-->A) (c.93-21G-->A) substitution identified in 4 out of 402 chromosomes (1%). In the province of Lushnja, the frequency of beta-thalassaemia carriers was high. As expected, the results show that identified mutations in this population are similar to those found in the east Mediterranean area, suggesting the same origin for mutant alleles during migratory streams. Implementation of a routine carrier-screening programme is significantly facilitated by the presence of only two mutations and would be a wise approach to prevent beta-thalassaemia in the region.