Selective newborn screening of inborn errors of amino acids, organic acids and fatty acids metabolism in the Kingdom of Bahrain.

Mandatory newborn screening for metabolic disorders has not been implemented in most Middle Eastern countries. Early detection and treatment of inborn errors of metabolism can reduce mortality and minimize morbidity. Preliminary studies conducted in some parts of Middle East suggest that the incidences of inborn errors of metabolism are reported to be higher in the region than anywhere else in the world due to the consanguinity. In this study the incidence of inborn errors of amino acids, organic acids and fatty acids oxidation disorders was investigated from the results of blood spot analysis of 1986 symptomatic children from 1st January 2008 to 31st of December 2011. Out of 1986 newborns screened 25 infants were diagnosed and confirmed with amino acids (n=11), organic acids (n=9) and fatty acids oxidation (n=5) disorders. Overall incidences based on number of live birth between 2008 and 2011 inclusive were 1:6000, 1:8000 and 1:14,000 for amino acids, organic acids and fatty acids oxidation disorders; respectively. Out of 25 infants diagnosed, 21 were the children of first cousin marriages. Results from this study suggest high incidence of inborn errors of amino acids, organic acids and fatty acids oxidation metabolism in Bahrain and significant contribution of consanguinity in inherited metabolic disorders. Mandatory screening for inborn errors of metabolism in Bahrain is highly recommended.

Students' perceptions of the effectiveness of a professional skills program in preparation for clerkship training.

CONTEXT: The goal of the Professional Skills Program at Arabian Gulf University, Bahrain, is to prepare medical students for the clerkship phase. In the six-year integrated problem-based learning (PBL) medical program, the Professional Skills Program is introduced in years two to four. The aim of this study was to evaluate program effectiveness as perceived by the students in the clerkship phase. METHOD: Students' perceptions were obtained using a mailed questionnaire. Close-ended questions were assessed using a 5-point Likert scale. Students were also asked to comment on areas of strengths or suggestions for improvement. The questionnaire was piloted with a group of students in the clerkship years. Results were analyzed in relation to the different domains of the program. RESULTS: Students were positive about their clinical skills training in preparing them for their clerkship in relation to three levels of Kirkpatrick outcome measures. This was particularly true for the domains of physical examination and procedural skills. However, they indicated some areas in need of program development, particularly in the history-taking domain. CONCLUSION: The students' opinions generally support the effectiveness of the Professional Skills Program training in preparing them for the clerkship phase. Program evaluation has helped us to plan for further development of the program.

Clinical, biochemical, and molecular characterization of patients with glutathione synthetase deficiency.

Pyroglutamic aciduria (5-oxoprolinuria) is a rare autosomal recessive disorder caused by either glutathione synthetase deficiency (GSSD) or 5-oxoprolinase deficiency. GSSD results in low glutathione levels in erythrocytes and may present with hemolytic anemia alone or together with pyroglutamic aciduria, metabolic acidosis, and CNS damage. Five patients with pyroglutamic aciduria were studied. All presented with hemolytic anemia and metabolic acidosis. Two (brothers) also had Fanconi nephropathy, which is not seen in pyroglutamic aciduria. Molecular analyses of the GSS gene was performed in 3 patients. RT-PCR and heteroduplex analysis identified a homozygous deletion in 1 patient and a homozygous mutation in 2 others (brothers with Fanconi nephropathy). Sequencing of glutathione synthetase (GSS) cDNA from the first patient showed a 141-bp deletion corresponding to the entire exon 4, whilst the corresponding genomic DNA showed a G491 --> A homozygous splice site mutation. Sequencing of GSS cDNA from the Fanconi nephropathy patients showed a C847 --> T [ARG283 --> CYS] mutation in exon 9.

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.

Infectious complications of propionic acidemia in Saudia Arabia.

A retrospective study of 38 patients with propionic acidemia indicates a high frequency of infections; affecting 80% of such patients. The Saudi Arabian population studied is a product of consanguineous marriages, and presents with a severe phenotype. Most microorganisms implicated are unusual, which suggests an underlying immune deficiency. These frequent infections occur despite aggressive treatment with appropriate diets, carnitine and during acute episodes of the disease with metronidazole, which suggests a global effect of the disease on T and B lymphocytes as well as on the bone marrow cells. Any patient with propionic acidemia should be closely followed up for an intercurrent infection in association with acute metabolic decompensation.

Biotin-responsive basal ganglia disease: a novel entity.

We describe a novel, biotin-responsive basal ganglia disease in 10 patients. At onset, it appears as a subacute encephalopathy, with confusion, dysarthria and dysphagia with occasional supranuclear facial nerve palsy or external ophthalmoplegia, and progresses to severe cogwheel rigidity, dystonia and quadriparesis. These symptoms disappear within a few days if biotin (5-10 mg/kg/day) is administered, and there are no neurological sequelae. They reappear within 1 month if biotin is discontinued. Patients diagnosed late, or who have had repeated episodes, suffer from residual symptoms such as paraparesis, mild mental retardation or dystonia. The numerous biochemical studies of intermediary metabolism, like the autoimmune and toxicological studies, enzyme assays including biotinidase, carboxylase and lysosomal activities, and bacterial and viral studies were all normal. The aetiology may be related to a defect in the transporter of biotin across the blood-brain barrier. The only consistent radiological abnormality was central necrosis of the head of the caudate bilaterally and complete, or partial, involvement of the putamen on brain MRI. This was present during the initial acute encephalopathy and remained unchanged during follow-up of 3-10 years. Although its aetiology is unknown, it is important to recognize this disease, since its symptoms may be reversed and the progression of its clinical course prevented simply by providing biotin.