Mutations in three different genes of phosphorylase kinase (Phk) subunits, PHKA2, PHKB and PHKG2, can give rise to glycogen storage disease of the liver. The autosomal-recessive, liver-specific variant of Phk deficiency is caused by mutations in the gene encoding the testis/liver isoform of the catalytic gamma subunit, PHKG2. To facilitate mutation detection and to improve our understanding of the molecular evolution of Phk subunit isoforms, we have determined the structure of the human PHKG2 gene. The gene extends over 9.5 kilonucleotides and is divided into 10 exons; positions of introns are highly conserved between PHKG2 and the gene of the muscle isoform of the gamma subunit, PHKG1. The beginning of intron 2 harbors a highly informative GGT/GT microsatellite repeat, the first polymorphic marker in the PHKG2 gene at human chromosome 16p11.2-p12.1. Employing the gene sequence, we have identified homozygous translation-terminating mutations, 277delC and Arg44ter, in the two published cases of liver Phk deficiency who developed cirrhosis in childhood. As liver Phk deficiency is generally a benign condition and progression to cirrhosis is very rare, this finding suggests that PHKG2 mutations are associated with an increased cirrhosis risk.

Wilson disease (WD) is a hereditary disorder, with recessive transmission and genetic heterogeneity. Several mutations of ATP7B, the gene underlying WD, were reported in many ethnic groups. In this study, mutation screening in ATP7B of 56 Saudi Arabian WD patients was undertaken. The clinical data of all patients were recorded. The entire ATP7B coding sequence, including intron-exon boundaries were screened for mutation by the polymerase chain reaction (PCR)-based mutation detection technique and DNA sequencing. Thirty-nine patients were symptomatic at presentation and 17 subjects were pre-symptomatic siblings of affected patients. Fourteen patients had neurological, 11 patients had mixed (hepatic and neurological), and 14 patients had hepatic presentations. Family history suggestive of WD was present in 72% of cases and 68% had consanguineous parents. Genetic analysis showed disease-causing mutations in three exons (exons 8, 19 and 21) of the ATP7B gene in 28 patients (50%). Mutations in exons 21 (18 cases) and 19 (one case) were unique for Saudis. This large series of Saudi patients with WD has shown wide variability in the genomic substrate of WD. There is no correlation between genotype and clinical presentation.

OBJECTIVE: To identify the risk factors, characteristics and outcomes of necrotizing enterocolitis (NEC) at our institution. STUDY DESIGN: A retrospective case-control analysis of the charts of all late preterm and term infants, who had NEC of Bell's stage ≥ II from 1995 to 2009, along with infants of the same gestational age. Thirty-two late preterm infants had NEC meeting criteria and 128 late preterm and term infants were chosen as matched controls. RESULTS:The 32 NEC infants were more likely to have the following characteristics: a culture-proven sepsis (p = 0.0001), be small for their gestational age (p = 0.003), have a congenital heart disease (p = 0.007), and suffer from hypoxic-ischemic encephalopathy (p = 0.04). The presence of hypotension, metabolic acidosis, thrombocytopenia, and pneumoperitoneum was associated with a poor prognosis. Twelve of the 13 (92%) NEC infants who died had a surgical intervention. CONCLUSION: In this study, late preterm and term infants who developed NEC had other underlying clinical diagnoses and had culture-proven sepsis. Mortality rate was high in infants who required surgical intervention, indicating that they were gravely ill from the onset. Thrombocytopenia, hypotension and metabolic acidosis in late preterm and term infant with NEC were associated with poor prognosis.

We have correlated flow abnormalities in the hepatic vasculature with histological findings in the liver to determine the accuracy of Doppler ultrasound in the diagnosis of liver cirrhosis in children. Eighteen children admitted for evaluation of unknown liver disease were examined prospectively and blindly with Doppler ultrasound prior to liver biopsy. Biopsy specimens showed established cirrhosis in 9 of 18, early cirrhosis in 5 of 18, and no cirrhosis in 4 of 18 children. Doppler studies were also performed on 20 control subjects. The portal vein velocity was decreased (p < 0.0005) and the arterio‐portal velocity ratio was increased (p < 0.0005) in the established cirrhosis cohort relative to the controls. For the criteria of the established cirrhosis cohort, the sensitivities of the loss of the reverse flow component in the hepatic veins, the arterio‐portal velocity ratio being greater than 3.0, the portal vein velocity being less than 20 cm/s, and the existence of focal flow acceleration in the hepatic veins were 100%, 78%, 67%, and 44%, respectively. The specificity of all of these criteria was 100%. The indicators were not useful in the diagnosis of early cirrhosis. © 1996 John Wiley & Sons, Inc.

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