Unraveling Alström syndrome: Homozygous mutation c.2729C>G in ALMS1 gene across an extended family.

BACKGROUND: Alström syndrome (AS) represents an exceptionally rare genetic disorder characterized by a constellation of features including cardiomyopathy, progressive hearing and vision impairment, as well as obesity. This study seeks to elucidate the genetic underpinnings of this syndrome within the Saudi Arabian population. METHODS: Employing an extended family cohort, we conducted an exhaustive molecular genetic assessment to delineate the presence of Alström syndrome. Additionally, we conducted an extensive review of existing literature from Saudi population to contextualize our findings within the broader understanding of the disorder in our country. RESULTS: Within our studied extended family, we identified two individuals harboring the homozygous pathogenic mutation (c.2729C>G) in the ALMS1 gene [NM_015120.4:c.2729C>G (p.Ser910*)]. Notably, carrier status was observed in the parents, whereas some siblings exhibited typical alleles while others were carriers of the mutation. Intriguingly, a review of the literature unveiled six distinct reports documenting a total of 20 Alström syndrome patients within the Saudi Arabian population, each presenting with distinct novel mutations. CONCLUSIONS: In cases featuring cardiomyopathy, obesity, and progressive hearing and vision loss, Alström syndrome merits inclusion within the differential diagnosis. To confirm the diagnosis, molecular genetic assessment of the ALMS1 gene is imperative, offering definitive clarity amidst the complex clinical presentation. This investigation reinforces the importance of genetic scrutiny for precise diagnosis and highlights the unique genetic landscape of Alström syndrome within the Saudi Arabian population.

"Progressive myoclonic ataxia and developmental/epileptic encephalopathy associated with a novel homozygous mutation in TCN2 gene".

BACKGROUND: Transcobalamin II (TCN2) defect is a rare metabolic disorder associated with a range of neurological manifestations, including mild developmental delay, severe intellectual disability, ataxia, and, in some cases, seizures. Cobalamin, an essential nutrient, plays a crucial role in central nervous system myelination. CLINICAL PRESENTATION: We present a family with an index patient who exhibited progressive neurodevelopmental regression starting at 9 months of age, accompanied by myoclonic seizures, ataxia, and tremor. No significant hematological abnormalities were observed. Exome sequencing analysis identified a novel homozygous mutation, c.3G>A - P(Met1I), affecting the acceptor site of intron 4 of the TCN2 gene (chromosome 22: 31003321, NM_000355.4), leading to likely pathogenic variant potentially affecting translation. Following treatment with hydroxocobalamin, the patient demonstrated partial clinical improvement. He has a sibling with overt hematological abnormalities and subtle neurological abnormalities who is homozygous to the same mutation. Both parents are heterozygous for the same mutation. CONCLUSIONS: In infants presenting with unexplained non-specific neurological symptoms, irrespective of classical signs of vitamin B12 deficiency, evaluation for TCN2 defect should be considered. Early diagnosis and appropriate management can lead to favorable outcomes.

Does Aerobic Vaginitis Have Adverse Pregnancy Outcomes? Prospective Observational Study.

Background: Aerobic vaginitis (AV) is an aberration within the balanced vaginal microbiota. Only few reports have documented the adverse pregnancy outcomes related to AV. Nonetheless, the exact role of AV in pregnancy and the potential benefit of its screening need further study. Our goal was to evaluate the association between aerobic vaginitis (AV) in late pregnancy and maternal and neonatal outcomes. Methods: In this prospective observational study, a total of 600 singleton pregnant women with intact fetal membranes at a gestational age of 34-36 weeks were recruited (one hundred women with AV and 500 pregnant women without AV). The study protocol excluded patients with other forms of vaginal infection. Pregnancy outcomes were traced and documented. The primary outcome was the association between AV and preterm labor. The current study compared the maternal and neonatal outcomes among pregnant women with and without AV in unadjusted and adjusted analyses with the odds ratio (OR) and 95% confidence interval (CI) reported. Results: There was an association between AV and with preterm birth (adjusted OR 3.06, 95% CI 1.58-5.95) and prelabor rupture of membranes (adjusted OR 6.17, 95% CI 3.24-11.7). For neonatal outcomes, AV was associated with a higher incidence of neonatal ICU admission (adjusted OR 2.19, 95% CI 1.1-4.34). Severe forms of AV significantly increased the incidence of PTB (p = 0.0014) and PROM (p = 0.0094) when compared to less severe forms of AV. Conclusion: AV is common in late pregnancy and is linked to a diversity of adversative pregnancy outcomes including preterm birth, PROM, and neonatal ICU admission. Moreover, the incidence of PTB and PROM might further increase with the severity of AV. Clinicians should pay more consideration to vaginal microbiota assessment during pregnancy.

Serial serum alkaline phosphatase as an early biomarker for osteopenia of prematurity.

Metabolic bone disease of prematurity is a condition characterized by reduction in bone mineral content (osteopenia). It is a problem faced by very low birth weight (VLBW) infants because of lack of fetal mineralization during the last trimester. Our aim was to assess serum alkaline phosphatase (ALP) level as an early biomarker for osteopenia in premature infants and to estimate an optimal cutoff value of serum ALP at which osteopenia is detected radiologically in premature newborns.This prospective study was conducted on a cohort of 120 newborn infants of both sex of ≤34 weeks' gestational age and <1500 g birth weight. Two blood samples, from each infant on at least 2 consecutive weeks, were reported for calcium, phosphorus, and ALP. Evidence of osteopenia was evaluated radiologically by performing wrist/knee x-ray.Sixteen infants (13.3%) had evidence of osteopenia in x-ray, whereas 104 infants (86.7%) were nonosteopenic and all the osteopenic infants were <1000-g birth weight. Birth weight and gestational age were significantly inversely related to serum ALP levels. Both samples showed statistically significantly higher mean ALP level in osteopenic than nonosteopenics (P < 0.001, and P < 0.001 respectively). There was no constant value of serum ALP related to radiologic evidence of osteopenia. However, the optimal cutoff value of serum ALP at which osteopenia is detected is 500 IU/L with 100% sensitivity and 80.77% specificity.High levels of ALP can be considered a reliable biomarker to predict the status of bone mineralization and the need for radiological evaluation in premature infants particularly those <1000-g birth weight and <32 weeks' gestation.

Arginine dimethylation products in pediatric patients with chronic kidney disease.

BACKGROUND: arginine and its metabolites have been linked to pediatric chronic kidney disease (CKD). We aimed to estimate serum levels of argninine (Arg), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) in pediatric CKD patients and its relation to altered kidney function. PATIENTS AND METHODS: 132 pediatric patients with CKD and 120 healthy age and sex matched controls were compared regarding; serum Arg, ADMA and SDMA levels. RESULTS: In comparison to their values in control subjects, serum Arg levels were significantly lower; serum ADMA levels were non-significantly higher, but serum SDMA levels were significantly higher in CKD patients (p values: < 0.000; = 0.054; <0.000, respectively). Calculated Arg/ADMA and Arg/SDMA ratios were significantly higher in patients compared to controls (p values: 0.001, and <0.000, respectively). However ADMA/SDMA ratio was significantly lower in patients compared to controls (p = 0.001. Serum Arg levels showed positive significant correlation, while serum ADMA and SDMA levels showed negative significant correlation with eGFR. Moreover, Arg/ADMA ratio showed negative significant correlation, while ADMA/SDMA ratio showed positive significant correlation with eGFR of patients. Regression analysis defined high serum SDMA level as persistently significant predictor for low eGFR. CONCLUSION: Disturbed serum levels of arginine and its dimethyl derivatives may underlie development and/or progression of CKD. Elevated serum SDMA level is strongly correlated with impaired kidney functions and could be considered as a predictor for kidney functions deterioration and CKD progression.

Early detection of myocardial dysfunction in poorly treated pediatric thalassemia children and adolescents: Two Saudi centers experience.

BACKGROUND & OBJECTIVE: Cardiac complications are among the most serious complications in Beta Thalassemia Major Patients. Our aim was to evaluate the value of tissue Doppler imaging (TDI) for early detection of myocardial dysfunction in pediatric and adolescent patients with B-TM before development of overt heart failure or cardiomyopathy. PATIENTS AND METHODS: 100 thalassemic patients below 18 years old and 100 healthy, age & sex matched controls were enrolled in our case-control study. Cases were selected from those attending outpatient clinics and inpatient wards, King Abdulaziz University hospital and Alhada Armed Forces Hospital, Saudi Arabia, between January 2014 and January 2015. They were subjected to echo-Doppler examination for both septal and lateral walls of the basal mitral and tricuspid annuli assessing the systolic myocardial velocity (S wave), early diastolic myocardial velocity (Ea wave) and late diastolic myocardial velocity (Aa wave). RESULTS: Patients with thalassemia have RV and LV dysfunction on the basis of abnormal TDI derived myocardial velocities. There was a statistically significant differences between patients and controls regarding (Aa) and (S) of the septal wall of the basal mitral annulus and (Ea) of the lateral wall of the mitral annulus. Also patients with thalassemia have significantly higher (S) of the basal tricuspid annulus. These abnormalities were not detected by conventional echo-Doppler. CONCLUSION: Clinically asymptomatic thalassemic children and adolescents who had normal global functions by conventional echo-Doppler were found to have abnormal left ventricular and right ventricular dysfunctions detected by TDI. TDI is superior to Echo-Doppler in detection of early myocardial damage in asymptomatic thalassaemic patients.

First report of co-morbidity of pantothenate kinase-associated neurodegeneration and three types of chronic hemolytic anemias.

BACKGROUND: Pantothenate kinase-associated neurodegeneration (PKAN), sickle cell anemia, and thalassemia are autosomal recessive disorders that can cause iron deposition in tissues during childhood. PKAN is characterized by accumulation of iron in the basal ganglia causing progressive extrapyramidal manifestations. Thalassemia and sickle cell disease can cause iron overload and deposition in tissues, including central nervous system. PRESENTATION OF CASE: we herein report the first report of comorbidity of PKAN, ß-thalassemia-major, sickle cell and glucose-6-phosphate dehydrogenase deficiency (G6PD) anemias in a 9 years old Saudi female patient who presented with gait disturbance, speech difficulty, and progressive movement disorders of the neck, upper and lower limbs. CONCLUSION: Although extremely rare, ß-thalassemia-major, sickle cell and G6PD anemias can be associated with PKAN. It is unknown whether this association is random or due to an unknown factor that may have caused several mutations.

Outcomes of Early Ligation of Patent Ductus Arteriosus in Preterms, Multicenter Experience.

Persistent ductal patency may have serious effects in preterm infants. Analysis of the results of different trials were inconclusive in determining whether medical or surgical closure of the ductus is preferable and what is the best timing for surgical intervention.The aim of this study was to evaluate the effect of timing of surgical closure of patent ductus arteriosus (PDA) on ventilatory, hemodynamic, and nutritional status of preterm infants.The authors retrospectively looked at the outcomes of surgical ligation of PDA from January 2010 to June 2014 at 2 Saudi neonatal intensive units at 2 tertiary care centers and the authors compared the results of early ligation (before 3 weeks) to the late ligation (after 3 weeks) regarding different hemodynamic, ventilatory, and nutritional parameters.A total of 120 preemies were included (75 preemies with early ligation and 45 with late ligation of PDA). The early ligation group had shorter duration of assisted ventilation of 10 (8-37) days as compared with 37 (26-90) days in the late ligation group (P < 0.05). The median fraction of inspired oxygen, needed to maintain good oxygen saturation in patients, was higher in the late ligation group [0.29 (0.21-0.70)] than in the early group [0.23 (0.21-0.55)] at 24  hours postoperatively. Full oral feeding was achieved earlier in the early ligation group than in the late group, 29 (15-73) days of life versus 53 (34-118) days of life, respectively (P < 0.05). Body weight at 36 weeks postconceptional age was higher in the early group--2100 (1350-2800) g--than in the late group-1790 (1270-2300) g--(P < 0.05).Our study demonstrated that earlier surgical ligation of the PDA in preterm infants has a more favorable nutritional and ventilatory outcome.