Clinical, fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomography of the brain, MR spectroscopy, and therapeutic attempts in methylenetetrahydrofolate reductase deficiency.

The cases of three infants, two Saudi and one Bahraini, with methylenetetrahydrofolate reductase (MTHFR) deficiency are reported. They presented in the neonatal period with lethargy, poor feeding, hypotonia, and frequent apneas. Tandem mass spectrometry (MS/MS) of a blood spot indicated very low methionine level and of urine revealed high homocysteine. The diagnosis was confirmed by demonstrating severe deficiency of MTHFR in the cultured skin fibroblast. All patients were treated with folinic acid, vitamin B12, betaine, and methionine, with good initial response to the therapy. In two patients, the diagnosis was late and their disease was severe, resulting in neurological crippling. However, in the third patient, who was diagnosed and treated early, the current neurological status is normal. In her case, at 1 month of age, the brain FDG PET scan documented very faint cerebral and cerebellar cortical activities. After 5 months of intensive therapy, that included 200-600 mg/kg per day methionine, she had a dramatic clinical and biochemical recovery as well as a parallel improvement in FDG PET. Brain MR spectroscopy indicated normal neuronal glial and myelin markers for her age. We conclude that the functional changes confirmed by the FDG PET study were better correlated with the clinical course of the patient and adequately monitored the response to therapy. This disease warrants early detection through neonatal screening program, since the beneficial effect of early administration of adequate therapy with combined use of betaine and a high dose of methionine is rewarding and may be the treatment of choice for MTHFR deficiency.

Congenital cystic disease of the lung in infants and children (experience with 57 cases).

A retrospective analysis of 57 consecutive cases with congenital cystic disease of the lung admitted to King Faisal Specialist Hospital and Research Center and King Khalid University Hospital, Riyadh, between 1985-1995 is presented. There were 37 congenital lobar emphysema (CLE), 7 cystic adenomatoid malformation (CAM), 8 bronchogenic cyst (BC) and 5 pulmonary sequestrations (PS). There were 39 males and 18 females with ages ranging from 1 day to 5 years. All patients were symptomatic except three. Respiratory distress, repeated chest infections, and cystic changes noted in chest x-ray were the commonest presentation. Five of eight patients with BC presented with symptoms related to pressure effect of the cyst on the surrounding structures, these included bronchiectasis in two patients, bronchopleural fistula in one, pulmonary artery stenosis and bronchomalacia in one, airway obstruction mimicking bronchial asthma in one. Seven patients (12.2%) were treated conservatively, the remaining underwent surgery. Surgery included excision of the bronchogenic cyst and lobectomy for CLE, CAM, and intralobar sequestration. The post-operative course in most cases was uneventful. There were no deaths in this series, and the majority of patients had a satisfactory outcome with follow-up ranging from 1-72 months (mean 24 months). It appears that lobectomy for symptomatic CLE, CAM, and intralobar sequestration and excision for bronchogenic cyst offer the best treatment modality and is well tolerated by pediatric patients. Careful search for associated anomalies is important to obtain better outcome.

Cystic fibrosis in Saudi Arabia: common and rare presentations.

The clinical presentations of 12 children with cystic fibrosis seen in King Khalid University Hospital are presented. Ten were of Saudi origin and the other two were African. The mean age of onset of symptoms was 2.3 months, and the mean age at diagnosis was 14.3 months (range 3-48 months). Seven children were boys and five were girls. All children presented with growth failure, recurrent chest infection and chronic diarrhoea. The parents of 83% of our cases were first-degree relatives. Pseudo-Bartter syndrome was seen in eight children. Sixty-seven per cent of our cases were colonized with Pseudomonas aeruginosa by the time of diagnosis, despite their young age (mean 7 months). Peripheral neuropathy secondary to vitamin E deficiency, meconium ileus, nasal polyps and gall-stones were present, each in one case. On follow-up, one child died and the other 11 are still alive. We concluded that cystic fibrosis is not rare in Saudi Arabia and that increased awareness of the disease is needed to avoid delay in diagnosis. Efforts should be made to prevent early colonization by Pseudomonas aeruginosa.

Late pulmonary function following repair of tracheoesophageal fistula or esophageal atresia.

Although tracheoesophageal fistula and esophageal atresia (TEF-EA) are surgically correctable, late respiratory complications have been reported. We administered a respiratory and gastrointestinal symptom questionnaire and performed standard pulmonary function tests (PF T's) and methacholine challenge testing on an unselected group of 25 subjects with TEF-EA who underwent surgery at our institution between 1963 and 1985. Results were compared to predicted normals, as well as 10 sibling controls. While the mean values of lung function test results for the TEF-EA group were within the normal range, they were significantly different from their siblings. Thirteen of the 25 TEF-EA group (52%), but none (0%) of the controls, had abnormal pulmonary function. This was classified as restrictive in 9 (36%), obstructive in 3 (12%), and mixed in 1. In addition, airway hyperreactivity [defined as a positive methacholine challenge (PC20 < or = 8 mg/mL)], was found in 6 of 18 TEF-EA subjects and 4 of the 9 controls who were evaluated. Comparison of TEF-EA subjects with normal and abnormal PFTs showed no difference in the incidence of tracheomalacia, esophageal strictures or dilatation, recurrent pneumonias, or gastroesophageal reflux. The respiratory symptom score in the subjects and controls was similar, and did not correlate with abnormal pulmonary function. The cause of the pulmonary function abnormalities remains unexplained.

Risk of thrombocytopenia in the infants of mothers with idiopathic thrombocytopenia.

Twenty-nine of 27,662 pregnant women had autoimmune thrombocytopenia at the time of delivery at King Khalid University Hospital over 6 years starting June 1986. Twenty-six had idiopathic thrombocytopenic purpura (ITP), gave birth to 33 infants, of which 22 were by spontaneous vaginal delivery, eight by lower segment cesarean section, and two by forceps. Fourteen (44%) of the 32 living infants had platelets less than 150 x 10(9)/L and four (12.5%) had severe thrombocytopenia (platelets less than 50 x 10(9)/L). The mothers' platelets of less than 50 x 10(9)/L at delivery were found to be predictive of thrombocytopenia in their infants (P < 0.027), compared with mothers' platelet of more than 50 x 10(9)/L. Maternal treatment with prednisone did not seem to have significant effect on infants' platelets (P < 0.89). All infants with severe thrombocytopenia (less than 50 x 10(9)/L) at birth had ultrasound done and were found to be normal. We conclude that: (1) steroid given to pregnant women with ITP does not increase infants' platelet counts, (2) severe thrombocytopenia in the mothers (platelet counts less than 50 x 10(9)/L) is highly predictive of thrombocytopenia in their infants; (3) cesarean section should be limited to the mother with severe thrombocytopenia if fetal scalp platelets are less than 50 x 10(9)/L.

Cardiorespiratory fitness, physical activity patterns and coronary risk factors in preadolescent boys.

The relationships between cardiorespiratory fitness, daily physical activity, and selected coronary artery disease (CAD) risk factors were evaluated in a sample of 91 preadolescent boys. Cardiorespiratory fitness was assessed (VO2max). Physical activity level was assessed using daytime heart rate telemetry. CAD risk factors included total cholesterol, fasting triglycerides, HDL-cholesterol, LDL-cholesterol, fasting blood glucose, systolic and diastolic blood pressures, and body fat content. The mean value of VO2max exhibited significant negative relationship with body fat percent (r = -0.55). Controlling the effects of age, body mass index and body fat percent resulted in a significant inverse relationship between physical activity and systolic (r = -0.29) and diastolic (r = -0.28) blood pressures. Analysis of data by quartiles revealed significant differences only in body fat percent across fitness categories, while no significant differences were detected in the other CAD risk factors. However, higher HDL-cholesterol and lower triglycerides levels were observed in those boys with higher levels of physical activity. It was concluded that except with body fatness, cardiorespiratory fitness is not strongly associated with lower CAD risk factors, while physical activity level was significantly associated with lower blood pressure level but not with the other CAD risk factors.

Respiratory syncytial virus infection in young children hospitalized with respiratory illness in Riyadh.

The occurrence of respiratory syncytial virus (RSV) infection among young children hospitalized with lower respiratory tract illness, at King Khalid University Hospital in Riyadh, was examined during the autumn-winter season between September 1991 and February 1992. Sixty-nine cases were diagnosed by immunofluorescent antibody staining of viral antigen in nasopharyngeal aspirates from 127 children, constituting 54 per cent of these patients. Virus culture was attempted only in a few cases, yielding two isolates. Most children were < 1 year of age (median 2 months). Bronchiolitis and bronchopneumonia were the major diagnoses on admission. Hospitalization was for an average of 5 days (range 1-36 days). Treatment was supportive but most children received antibiotic therapy. There was no mortality. Few other bacterial or viral pathogens could be identified from RSV-positive or -negative patients. These results indicate that, during the season of infection, RSV may be the main pathogen of lower respiratory tract illness in hospitalized young children in this region.

Pancytopenia in children with brucellosis: clinical manifestations and bone marrow findings.

Among 276 paediatric cases of brucellosis seen over a 7-year period, 16 patients (5.8%) with pancytopenia were identified. The most frequent presentations were fever, malaise, anorexia, weight loss, arthralgia, and hepatosplenomegaly. Fourteen patients (87.5%) had positive blood and/or bone marrow cultures for Brucella melitensis. Bone marrow aspiration specimens showed hypercellularity in 14 patients and normocellularity in 2. Histiocytes, eosinophils and plasma cells were increased in every marrow aspirate, and haemophagocytosis was observed in 14 patients (87.5%). Non-caseating granulomas were present in the bone marrow biopsy of 11 patients (68.8%). The pancytopenia was transient, and resolved on treatment of the Brucella infection.