Intragenic homozygous deletions in the Large gene are associated with a severe neuromuscular phenotype in the myodystrophy (myd) mouse. These mutations result in a virtual lack of glycosylation of -dystroglycan. Compound heterozygous LARGE mutations have been reported in a single human patient, manifesting with mild congenital muscular dystrophy (CMD) and severe mental retardation. These mutations are likely to retain some residual LARGE glycosyltransferase activity as indicated by residual -dystroglycan glycosylation in patient cells. We hypothesized that more severe LARGE mutations are associated with a more severe CMD phenotype in humans. Here we report a 63-kb intragenic LARGE deletion in a family with WalkerWarburg syndrome (WWS), which is characterized by CMD, and severe structural brain and eye malformations. This Wnding demonstrates that LARGE gene mutations can give rise to a wide clinical spectrum, similar as for other genes that have a role in the post-translational modiWcation of the -dystroglycan protein.

In this retrospective study from Saudi Arabia, which is a rich and sunny country, we report our experience with 34 adolescents (20 females, 10 males) with rickets. The commonest cause was vitamin D deficiency (58.8%) followed by rickets due to low calcium intake (11.8%) and genetic causes, including possible 25-hydroxylase deficiency (8.8%). The etiology of nutritional rickets is multifactorial, including lack of sun exposure and inadequate calcium intake. The clinical symptoms were nonspecific and therefore cases in this country are either underdiagnosed or missed. Vitamin D deficient patients needed an average of 19 months of treatment before recovery. High dose vitamin D plus calcium supplementation are recommended for treatment. Measures to prevent rickets in all age groups including adolescents are suggested. Further studies on nutritional and genetic forms of rickets are recommended.

The causative microorganisms were cultured and recovered from cerebrospinal fluid in 105 of 161 children with bacterial meningitis in the Eastern Province of Saudi Arabia from July 1982 through June 1985. The bacteria grown included Hemophilus influenzae type b (Hib) in 44 patients, Streptococcus pneumoniae in 25 patients, and Neisseria meningitidis in 12 patients. These amounted to about 80% of all proved cases of childhood bacterial meningitis. In 56 of the 161 children, causative pathogens were not identified. However, the clinical presentation, signs, and CSF findings were compatible with the diagnosis of bacterial meningitis. Comparison of the age-specific occurrence of various causes of meningitis was made. Hib infection occurred primarily during infancy, although these organisms were not recovered from infants as young as 1 to 2 months of age. Fourteen percent of Hib strains were resistant to ampicillin.A Abomelha, SA Uduman, MF Saleh, S Al-Rajeh, MS Sibai, A Al-Agib, Childhood Bacterial Meningitis. 1988; 8(4): 274-278 MeSH KEYWORDS: Meningitis, bacterial-in infancy and childhood BACTERIAL MENINGITIS in children can lead to considerable mortality rates or to neurologic deficits, such as impaired motor and intellectual development, hearing and vision loss, seizures, and language disorders. 12 The outcome of bacterial meningitis in each child depends on various factors; these include the patient's age, the specific microbiologic agents, the duration of the illness before initiation of treatment, and any other underlying medical disorder. The physician caring for the child should be aware of the organisms prevalent in the vicinity and their antimicrobial sensitivity in order to initiate prompt and appropriate antibiotic therapy.The purpose of this study was to establish the cause of various types of bacterial meningitis occurring among children in the Eastern Province of Saudi Arabia. The clinical features of childhood meningitis and their age specificity and initial cerebrospinal fluid (CSF) findings were reviewed. Attention was also focused on the specific causes of bacterial meningitis in infants 1 to 2 months of age.

BACKGROUND: Methotrexate (MTX) embryopathy was described nearly 50 years ago, when this agent began to be used as a cancer treatment and abortifacient. In this report we describe a case with typical features of MTX syndrome together with new features to expand the phenotype. CASE: A 29-year-old woman decided to terminate her unwanted pregnancy because of ill health, as she had conceived soon after her last delivery by cesarian section. At 6 weeks of gestation, she took 2.5 mg of MTX 3 times a day for 7 days. The pregnancy termination failed, and the pregnancy was carried to term. A female infant was delivered who was growth retarded and had characteristic features of MTX embryopathy in addition to holoprosencephaly and other brain malformations, facial hypertrichosis, and long eyelashes-features that have not hitherto been described. CONCLUSIONS:We report the first case of holoprosencephaly in association with MTX exposure during the first 6 weeks of gestation. Physicians and the public should be aware of the effects of MTX on the fetus during pregnancy.