Spinal muscular atrophy genetic epidemiology and the case for premarital genomic screening in Arab populations.

BACKGROUND: Spinal muscular atrophy (SMA) is a fatal autosomal recessive disorder for which several treatment options, including a gene therapy, have become available. SMA incidence has not been well-characterized in most Arab countries where rates of consanguinity are high. Understanding SMA disease epidemiology has important implications for screening, prevention, and treatment in those populations. METHODS: We perform SMA diagnostic testing in a clinical multi-national patient cohort (N = 171) referred for hypotonia and/or muscle weakness. In addition, we carry out genetic newborn screening for SMA on 1502 healthy Emirati newborns to estimate the carrier frequency and incidence of the disease in the United Arab Emirates. RESULTS: Patients referred for SMA genetic testing are mostly Arabs (82%) representing 18 countries. The overall diagnostic yield is 33.9%, which is higher (>50%) for certain nationalities. Most patients (71%) has two SMN2 copies and earlier disease onset. For the first time, we estimate SMA carrier frequency (1.3%) and incidence of the disease (1 in 7122 live births) in the United Arab Emirates. Using birth and marriage rates in two Arab populations (United Arab Emirates and Saudi Arabia), as well as disease incidence in both countries, we show that, besides preventing new cases, premarital genetic screening could potentially result in around $8 to $324 million annual cost savings, respectively, relative to postnatal treatment. CONCLUSIONS: The SMA carrier frequency and incidence we document suggests high potential benefit for universal implementation of premarital genomic screening for a wide range of recessive disorders in Arab populations.

The occurrence of spinal muscular atrophy, a fatal genetic nerve and muscle disease, has been poorly studied in most Arab countries. Individuals who carry a single mutated gene copy (carriers) may be more likely to marry other carriers in regions where marriage rates amongst relatives, who share similar genetics, are high. Here we report the results of a newborn testing program for this disease in 1502 Emiratis and calculate the presence of carriers (1/79) and occurrence of disease (1/7122) in this population. Using this new information along with the annual birth and marriage rates in the United Arab Emirates and Saudi Arabia, we make the case that premarital genomic screening (carrier testing) is the best way to prevent this and other similarly inherited disorders in the Arab population.

Subcutaneous Fat Necrosis of the Newborn After Whole-Body Cooling for Birth Asphyxia.

Therapeutic hypothermia (TH) is a challenging treatment for a neonate who suffers from hypoxic-ischemic encephalopathy. It has been shown to improve neurodevelopmental outcomes and survival in infants with moderate-to-severe hypoxic-ischemic encephalopathy. However, it has severe adverse effects such as subcutaneous fat necrosis (SCFN). SCFN is a rare disorder that affects term neonates. It is a self-limited disorder but can have severe complications such as hypercalcemia, hypoglycemia, metastatic calcifications, and thrombocytopenia. In this case report, we present a term newborn who developed SCFN after whole-body cooling.

Salbutamol versus cation-exchange resin (kayexalate) for the treatment of nonoliguric hyperkalemia in preterm infants.

Our objective was to compare the efficacy and safety of rectal cation-exchange resin (Kayexalate) versus salbutamol infusion for the treatment of nonoliguric hyperkalemia (NOHK) in preterm infants. Data of all neonates born with NOHK during the study period of 6 years and 8 months were recorded. Diagnostic criteria of NOHK included serum potassium (SK) concentration > or = 7 mmol/L during the first 72 hours of life with urine output > or = 1 mL/kg/hour. This before-after study was divided according to the date of admission; the first 15 patients were treated with Kayexalate enema 1 g/kg every 4 hours, and the remaining 30 patients were treated with intravenous salbutamol infusion as 4 mug/kg every 4 hours. Treatment discontinued when SK became < 6 mmol/L. SK was measured every 4 hours. Daily urine was collected. Fluid intake and output, serum electrolytes, urea, creatinine, and glucose concentrations were obtained in all infants every 12 hours. All infants were observed with a cardiorespiratory monitor and oxygen saturation and blood pressure measurements. Perinatal characteristics in both groups were comparable. Mean gestational age was 26 and 28 weeks for salbutamol and Kayexalate, respectively. The peak of SK ranged between 7 and 9.3 mmol/L in the Kayexalate group and between 7 and 8.7 mmol/L in the salbutamol group ( P = 0.64). At 12 hours of treatment, SK became normal in only 4 patients (26%) in the Kayexalate group compared with 18 patients (60%) in the salbutamol group ( P = 0.003). The number of doses of Kayexalate administration was significantly higher than the doses of salbutamol ( P = 0.003). No significant side effects were detected in the salbutamol-treated infants. In contrast, there were two cases of severe ventricular tachycardia and one case of intestinal obstruction in the cation-exchange resin group. We concluded that salbutamol infusion is more effective with faster action and safer than cation-exchange resin (Kayexalate) for the treatment of NOHK in preterm infants.

Does prophylactic phototherapy prevent hyperbilirubinemia in neonates with ABO incompatibility and positive Coombs' test?

OBJECTIVE: The objective of the study was to determine whether initiation of early phototherapy in positive direct Coombs' test (DCT) with ABO-incompatible newborns would prevent severe jaundice. STUDY DESIGN: A prospective controlled study was performed at Al Qassimi Hospital. Infants born at term and weighing >2000 g with ABO incompatibility and a positive DCT were included in the study. Within their first 4 hours of life and after parental consent, infants were enrolled into one of two groups: prophylactic phototherapy group, which received phototherapy during the first 24 hours of life (group I), or no prophylactic phototherapy, which represents the control group (group II). Selection of infants to either group was by 2-week alternative strategy. Blood group, complete blood count (CBC), reticulocyte count, blood smears, total serum bilirubin (TSB) and DCT were performed on cord blood of all neonates born to mothers with O-positive blood group. CBC, reticulocytes and TSB level were obtained in all enrolled infants at 12, 24, 48, 72, and 96 hours of life. RESULTS: During the study period, 242 newborns with positive DCT were enrolled. A total of 102 infants were allocated to the prophylactic phototherapy arm and 140 as controls. Prophylactic phototherapy was associated with a significant decrease in the TSB at 24 hours (p=0.002) and at 48 hours (p=0.003) but not later on. The total number of patients who had hyperbilirubinemia at any time during the first 96 hours was significantly less in the prophylactic group (17 vs 45--p=0.006). Prolonged hospital stay because of phototherapy was more frequent in the control group (p=0.03). CONCLUSION: Prophylactic phototherapy was associated with a significant reduction of TSB in the first 48 hours of life but not later on. Clinical benefits of this strategy could not be proven.