On the phenotypic spectrum of serine biosynthesis defects.

L-serine is a non-essential amino acid that is de novo synthesized via the enzymes phosphoglycerate dehydrogenase (PGDH), phosphoserine aminotransferase (PSAT), and phosphoserine phosphatase (PSP). Besides its role in protein synthesis, L-serine is a precursor of a number of important compounds. Serine biosynthesis defects result from deficiencies in PGDH, PSAT, or PSP and have a broad phenotypic spectrum ranging from Neu-Laxova syndrome, a lethal multiple congenital anomaly disease at the severe end to a childhood disease with intellectual disability at the mild end, with infantile growth deficiency, and severe neurological manifestations as an intermediate phenotype. In this report, we present three subjects with serine biosynthesis effects. The first was a stillbirth with Neu-Laxova syndrome and a homozygous mutation in PHGDH. The second was a neonate with growth deficiency, microcephaly, ichthyotic skin lesions, seizures, contractures, hypertonia, distinctive facial features, and a homozygous mutation in PSAT1. The third subject was an infant with growth deficiency, microcephaly, ichthyotic skin lesions, anemia, hypertonia, distinctive facial features, low serine and glycine in plasma and CSF, and a novel homozygous mutation in PHGDH gene. Herein, we also review previous reports of serine biosynthesis defects and mutations in the PHGDH, PSAT1, and PSPH genes, discuss the variability in the phenotypes associated with serine biosynthesis defects, and elaborate on the vital roles of serine and the potential consequences of its deficiency.

Neu-Laxova syndrome, an inborn error of serine metabolism, is caused by mutations in PHGDH.

Neu-Laxova syndrome (NLS) is a rare autosomal-recessive disorder characterized by severe fetal growth restriction, microcephaly, a distinct facial appearance, ichthyosis, skeletal anomalies, and perinatal lethality. The pathogenesis of NLS remains unclear despite extensive clinical and pathological phenotyping of the >70 affected individuals reported to date, emphasizing the need to identify the underlying genetic etiology, which remains unknown. In order to identify the cause of NLS, we conducted a positional-mapping study combining autozygosity mapping and whole-exome sequencing in three consanguineous families affected by NLS. Surprisingly, the NLS-associated locus identified in this study was solved at the gene level to reveal mutations in PHGDH, which is known to be mutated in individuals with microcephaly and developmental delay. PHGDH encodes the first enzyme in the phosphorylated pathway of de novo serine synthesis, and complete deficiency of its mouse ortholog recapitulates many of the key features of NLS. This study shows that NLS represents the extreme end of a known inborn error of serine metabolism and highlights the power of genomic sequencing in revealing the unsuspected allelic nature of apparently distinct clinical entities.

Hospital-acquired malaria transmitted by contaminated gloves.

We describe two cases of malaria occurring in a malaria-free zone in two in-patients, two weeks after a case of Plasmodium falciparum malaria, acquired in Burkina Faso, had been admitted to the same ward. After reviewing the techniques used by nursing staff, we conclude that transmission probably occurred via gloves contaminated following manipulation of venous cannulae and drip lines of the patient with Burkina Faso-acquired malaria and which had not been discarded before manipulating the intravenous lines of the other two patients. Nosocomial transmission of unusual and potentially life-threatening infections should be taken into consideration in those settings where compliance with universal precautions is not rigorous.

The nutritive value of new and traditional sorghum and millet foods from Sudan.

In the present study was examined the nutritive value of different sorghum and millet based baby foods. Different types of kisra, some fortified with chickpeas or peanuts, were also included in the study. Finally was compared the influence of replacing wheat bran with sorghum bran in bread. The nutritive value was assessed by chemical analyses and by rat balance studies. The addition of chickpea and peanuts improved the quality of kisra a staple food of Sudan. This type of kisra can be used as a well-balanced food for infants above the age of one year. The baby food developed from sorghum/millet malt, milk powder and processed by drum drier provides a safe level of protein for children above the age of one month. This formulation and way of processing is well suited for commercial production of sorghum/millet based baby food. Based on the results of the present investigation it is recommended that the use of brown bread for infants should not exceed ten percent wheat or sorghum bran as it affects the digestibility in a negative way.

The effects of sorghum and wheat bran on the colonic functions of healthy Sudanese subjects.

The effects of sorghum and wheat bran were compared and contrasted in a group of healthy Sudanese subjects. Ten medical students were studied while taking their normal diet, a diet of 20 g/day of sorghum bran and a diet of 20 g/day of wheat bran, each for 3 wk. Toward the end of each dietary period the wet stool weight, gut transit time, and frequency of bowel evacuation were estimated. The mean stool weight on normal diet was 136.6 +/- 43.1 g/day, on sorghum bran 173.3 +/- 48.4 g/day, and on wheat bran 219.1 +/- 98.3 g/day. The increase produced by wheat bran was significant, p less than 0.001. Both brans produced a similar number of bowel evacuations. The results suggest that sorghum bran, which is both cheap and readily available in the Sudan, produces a similar number of bowel evacuations to those of wheat bran without significantly affecting stool weight or transit time.