5-Oxoprolinase deficiency: report of the first human OPLAH mutation.

Gamma-glutamyl cycle is a six-enzyme cycle that represents the primary pathway for glutathione synthesis and degradation. 5-Oxoprolinase deficiency is an extremely rare disorder of the gamma-glutamyl cycle with only eight patients reported to date. Debate continues as to whether this is a benign biochemical defect because of the heterogeneity of the clinical presentation which ranges from normal to significant neurological involvement. Here, we report the first molecularly characterized patients with 5-oxoprolinase deficiency due to a mutation in OPLAH (which encodes 5-oxoprolinase). The largely benign clinical course of the patients described herein despite persistent 5-oxoprolinuria highlights the importance of establishing a molecular diagnosis in the few cases with abnormal neurological outcome to exclude potentially overlapping biochemical defects and to explore potential genotype/phenotype correlation.

Smith-Lemli-Opitz syndrome among Arabs.

Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disorder of variable presentation caused by the deficiency of the 3ß- hydroxycholesterol Δ(7) - reductase. Over the past 10 years, our biochemical laboratory has screened 191 plasma samples for possible SLOS, measuring the plasma cholesterol and 7-dehydrocholesterol using gas chromatography-mass spectrometry (GC-MS). The SLOS was confirmed in only five Arab patients with growth retardation, global developmental delay, dysmorphic features, and 2-3 toe syndactyly, among other findings. All cases represented moderate to severe form of SLOS. One patient had a unique cardiovascular malformation (cor triatriatum with significant obstruction of the right pulmonary veins). Two previously reported N287K (861 C>A) and R352Q (1055 G>A) and a novel R352L (1055 G>T) mutations were identified in the DHCR7 gene in these patients. The paper sheds light on this rare disease among Arabs and reviews all reported SLOS cases in the Arab population.

Carnitine palmityl transferase I deficiency.

Carnitine palmityl transferase I is the key enzyme in the carnitine dependent transport of long chain fatty acids across the mitochondrial inner membrane and its deficiency results in a decrease rate of fatty acids beta-oxidation with decreased energy production. We reported a family of 3 affected siblings who are the product of a first degree cousin marriage. The first 2 presented with typical Reye-like syndrome with unconsciousness, hepatomegaly, hypoglycemia, hyperammonemia and very high liver enzymes. Liver biopsy showed steatosis. On screening of the complete family, the 3rd sibling was found to have hepatomegaly. The 3 siblings showed an acyl carnitine profile with very high free carnitine with almost absent long chain acyl carnitines, suggestive of carnitine palmityl transferase I deficiency. This was confirmed by enzyme analyses in fibroblast cultures. These patients were effectively treated with a diet high in carbohydrate, low in long chain fatty acids with medium chain triglycerides. In conclusion, carnitine palmityl transferase I deficiency is an important cause of Reye-like syndrome, which may be treated easily with very good results if detected early in life.

Determination of L-pipecolic acid in plasma using chiral liquid chromatography-electrospray tandem mass spectrometry.

BACKGROUND: L-pipecolic acid (L-PA), an important biochemical marker for the diagnosis of peroxisomal disorders, is usually determined as the racemate. We developed a chiral liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the analysis of L-PA in plasma. METHODS: We used a narrow bore chiral macrocyclic glycopeptide teicoplanin column for the enantioseparation of D-pipecolic acid (D-PA) and L-PA and interfaced the column directly to the electrospray source of a tandem mass spectrometer. We used phenylalanine-d5 as internal standard added to 50 microL of plasma followed by deproteinization, evaporation, and injection. The analysis was performed in the selected-reaction monitoring mode using two transitions: m/z 130-->m/z 84 for PA, and m/z 171-->m/z 125 for phenylalanine-d5. L-PA eluted at 7 min, and D-PA eluted at 11.7 min, whereas phenylalanine-d5 eluted at 6 min. The turnaround time for the assay was 20 min. RESULTS: Linear calibration curves were obtained in the range of 0.5-80 micromol/L. At a plasma concentration of 1.0 micromol/L, the signal-to-noise ratio was 50:1. The intra- and interassay variations were 3.1-7.9% and 5.7-13%, respectively, at concentrations of 1-50 micromol/L. Mean recoveries of L-PA added to plasma were 95% (5 micromol/L) and 102% (50 micromol/L). The method clearly distinguished between healthy individuals and peroxisomal disease patients. CONCLUSIONS: The novel LC-MS/MS method is simple, rapid, and stereoselective, and uses only 50 microL of plasma, no derivatizing reagents, and a commercially available internal standard. Sample preparation is not complex and is faster than for all other methods.

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.

Two new species of Eimeria (Apicomplexa, Eimeriidae), from local chickens (Gallus domesticus) in Saudi Arabia.

In this study, two new species of Eimeria parasitizing domestic fowl (Gallus domesticus) are described. Species data were recorded as follow: Eimeria jeddahensis sp. n. with ovoidal occysts 23.5-29.2 x 17.5-22.4 (25.78 +/- 0.357 x 20.32 +/- 0.33) microns, with smooth single layered wall; bilobed polar granule and micropyle present. Sporocysts elongated ovoidal 10-13.5 x 6.3-8.0 (12.03 +/- 0.135 x 7.10 +/- 0.070) microns with a thick, knob like Stieda body and residuum. Eimeria waeli sp. n. with ellipsoidal oocysts 26.5-31.0 x 23.5-27.0 (28.30 +/- 0.327 x 25.30 +/- 0.278) microns with a double-layered wall; polar granule and micropyle present. Sporocysts ovoidal 13.5-16.0 x 7.0-9.5 (14.67 +/- 0.135 x 8.32 +/- 0.162) microns with distinct Stieda body and residuum. The host bird belongs to order Galliformes.

New records of Tabanidae (Diptera) from Saudi Arabia, first record of Atylotus venturii Leclercq and Tabanus separatus Efflatoun.

Atylotus venturii Leclercq and Tabanus separatu Efflatoun (Diptera: Tabanidae) are 2 additional species in Saudi Arabia; they lift up to 26 taxa known from the country. Some comments on new record of other species, zoogeographical distribution of Tabanus sufis, taxonomic significance of eye pattern of Tabanidae, exemplification with T. albifacies and T. unifasciatus, rehydration of dry specimens, are presented.

4-Hydroxybutyric aciduria.

The clinical findings in six patients from three families with 4-hydroxybutyric aciduria are described. The onset of disease was in early infancy in all cases. All infants presented with severe global delay and severe hypotonia, and all patients had seizure disorder. Eye findings included optic atrophy in two patients, and retinitis pigmentosa in one. Three patients had choreoathetosis, two had myoclonus and one had severe dystonia. The urine 4-hydroxybutyric acid was 300-1000 times that of normal, and other organic acids related to its further metabolism or to its inhibitory effect on beta-oxidation were also increased. The administration of vigabatrine rapidly reduced the excretion of 4-hydroxybutyric acid promptly, and in the long-term its excretion could be kept at 80-200 times that of normal. However, the clinical course of the disease improved in only two, remained the same in two, and worsened in the remaining two patients.

Development rate and mortality of immature Parasarcophaga (Liopygia) ruficornis (Diptera: Sarcophagidae) at constant laboratory temperatures.

Developmental time of Parasarcophaga ruficornis (F.) was determined at constant temperatures of 13, 16, 19, 22, 25, 28, 31, 34, and 37 degrees C. Estimates of the lower developmental threshold temperatures (tL) were 10.5, -7.0, 6.3, 8.8, and 7.7 degrees C and the thermal constants (K) were 65.15, 111.93, 152.13, 229.66, and 388.22 degree-days (DD) for feeding larvae, wandering larvae, larvae (feeding + wandering), pupae, and total developmental time, respectively. Flies reached their maximum weight in pupal and adult stages at 25 and 28 degrees C, whereas minimal weights were recorded at 16 and 37 degrees C. The optimal temperature in terms of rapid development, low mortality, and greatest weight ranged between 22 and 28 degrees C.

Effect of temperature on the developmental stages of Wohlfahrtia nuba (Diptera:Sarcophagidae).

Total developmental time of flesh flies Wohlfahrtia nuba (Wiedemann) from first larval stage to adult emergence was 34.7, 23.5, 18.7, 13.4 and 13.6 days when reared at 21, 25, 29, 33 and 37 degrees C, respectively. There were no significant differences between both sexes (P > 0.05). The overall mean of the larval duration periods was shorter (P < 0.05) than pupal duration periods. Estimates of the lower developmental threshold temperatures (tL) were 12.8, 14.0 and 13.6 degrees C and the thermal constant (K) were 116.8, 152.2 and 268.2 degree-days for larvae, pupae and total developmental time, respectively. Pupal mortality was low at all temperatures used. The fly reached their maximum weight in pupal and adult stages at 21 degrees C. At all temperatures, the mean weight of pupa and adult was smaller (P < 0.001) in males than in females. The developmental rate, low mortality and greatest weight reached their optimal condition between 21 to 33 degrees C.

New records of some of sarcophagid flies with distribution of all known flesh flies (Diptera:Sarcophagidae) of Saudi Arabia.

The Sarcophagidae (Flesh) of Saudi Arabia are reviewed based on collections of adult flies. Ten species of sarcophagid flies were recorded of which five are considered to be new record in Saudi Arabia. Checklist and information are given for each species concerning its geographical distributions and other observations.

First record of Glossina fuscipes fuscipes Newstead, 1910 and Glossina morsitans submorsitans Newstead, 1910 in southwestern Saudi Arabia.

Two species of tsetse flies, Glossina fuscipes fuscipes and G. morsitans submorsitans, are, for the first time, recorded from southwestern Saudi Arabia, near Gizan. This discovery is shortly discussed in relation with the presently known distribution of these species.

Two new species of Eimeria from peacocks (Pavo cristatus) in Saudi Arabia.

Fifteen fecal samples from peacocks (Pavo cristatus) in Saudi Arabia contained oocysts of Eimeria riyadhae n. sp. in two peacocks and oocysts of E. arabica n. sp. in one peacock. Sporulated oocysts of Eimeria riyadhae are ellipsoidal, 27-30.5 x 20.5-25 (28.8 +/- 1.3 x 22.4 +/- 1.6) micron, with a two-layered wall and bilobed polar body, but without a micropyle or residuum. The sporocysts are ovoid, 11-14.5 x 6.5-8 (13.2 +/- 1.2 x 7.2 +/- 0.6) micron with a thick, knob-like Stieda body and a residuum. Sporulated oocysts of Eimeria arabica are spheroidal, 17.5-21.5 x 17.5-21.5 (19.2 +/- 1.6 x 19.2 +/- 1.6) micron, with a two-layered wall and two refractile polar bodies, but without a micropyle or residuum. The sporocyts are elongate ovoid, 9.5-12 x 4-6.5 (11.2 +/- 0.9 x 5.5 +/- 0.88), with a small crescent-shaped Stieda body. The host bird belongs to the order Galliformis.

Two new species of Isospora from Indonesian birds.

The following species are described from Indonesian birds: Isospora paddae n. sp. with oocysts 41.5-45.5 x 40.3-41.5 (44 +/- 1.15 x 41.2 +/- 0.38) and sporocysts 22.8-24.5 x 14.7-17 (24 +/- 0.55 x 16.2 +/- 0.81) from the Java sparrow, Padda oryzivora, and Isospora indonesianensis n. sp. with oocysts 39.3-43.6 x 37-40.8 (41.8 +/- 1.3 x 39.6 +/- 1.25) and sporocysts 25.6-28.4 x 15.2-18.5 (27.1 +/- 1.05 x 16.8 +/- 1.22) from the chestnut Munia, Lonchura malacca (L). The host birds belong to the order Passerorida.

Eimeria tahamensis N. sp. (Apicomplexa: Eimeriidae) from the Arabian quail (Coturnix delegorguei arabica).

Eimeria tahamensis n. sp. is described from the harlequin quail (Coturnix delegorguei arabica) from Tahama, Saudi Arabia. The sporulated oocysts of E. tahamensis n. sp. are ellipsoid, 36.5-42 X 25.5-29 (41.2 +/- 1.34 X 28.4 +/- 0.81) micron, with a thick two-layered wall and one polar granule but without a micropyle or an oocyst residuum. The sporocysts are ovoid, 14-16 X 9-11.5 (15.3 +/- 0.7 X 10.8 +/- 0.64) micron, with a knob-like Stieda body and sporocyst residuum, but without a substiedal body. The sporozoites are often located transversely at the two ends of the sporocysts. The host bird belongs to the order Galliformes.

Isospora elmahalensis n. sp. (Apicomplexa, Eimeriidae), a parasite of the white-cheeked bulbul (Pycnonotus leucogenys) in Saudi Arabia.

Isospora elmahalensis n. sp. is described from the Saudi Arabian bird, Pycnonotus leucogenys, from the Elmahala valley. Sporulated oocysts of I. elmahalensis were spherical or nearly subspherical, 19.5-22.5 X 18.5-20 (21.34 +/- 0.4 X 19.06 +/- 0.5) microns. Oocysts lacked a micropyle, residuum, and polar granule. Sporocysts were ovoid, 14-17.5 X 7-12 (16.08 +/- 1.05 X 9.9 +/- 1.55) microns, and had a Stieda body and sporocyst residuum, but lacked a substiedal body. Sporozoites were elongated with a clear globule at one end. The host bird belongs to the order Passeriformes.