ABSTRACT
This study aimed to determine the mutation spectrum and prevalence of inborn errors of metabolism [IEM] among Emiratis. The reported mutation spectrum included all patients who were diagnosed with IEM [excluding those with lysosomal storage diseases [LSD]] at Tawam Hospital Metabolic Center in Abu Dhabi, United Arab Emirates, between January 1995 and May 2013. Disease prevalence [per 100,000 live births] was estimated from data available for 1995-2011. In 189 patients, 57 distinct IEM were diagnosed, of which 20 [35%] entities were previously reported LSD [65 patients with 39 mutations], with a birth prevalence of 26.87/100,000. This study investigated the remaining 37 [65%] patients with other IEM [124 patients with 62 mutations]. Mutation analysis was performed on 108 [87%] of the 124 patients. Five patients with biotinidase deficiency had compound heterozygous mutations, and two siblings with lysinuric protein intolerance had two homozygous mutations. The remaining 103 [95%] patients had homozygous mutations. As of this study, 29 [47%] of the mutations have been reported only in Emiratis. Two mutations were found in three tribes [biotinidase deficiency [BTD, c.1330G>C] and phenylketonuria [PAH, c.168+5G>C]]. Two mutations were found in two tribes [isovaleric aciduria [IVD, c.1184G>A] and propionic aciduria [PCCB, c.990dupT]]. The remaining 58 [94%] mutations were each found in individual tribes. The prevalence was 48.37/100,000. The most prevalent diseases [2.2-4.9/100,000] were biotinidase deficiency; tyrosinemia type 1; phenylketonuria; propionic aciduria; glutaric aciduria type 1; glycogen storage disease type Ia, and mitochondrial deoxyribonucleic acid depletion. The IEM birth prevalence [LSD and non-LSD] was 75.24/100,000. These results justify implementing prevention programmes that incorporate genetic counselling and screening
ABSTRACT
This study investigated the feasibility of using a phosphorescence oxygen analyser to measure cellular respiration [mitochondrial O[2] consumption] in foreskin samples and their fibroblast-rich cultures. Foreskin specimens from normal infants were collected immediately after circumcision and processed for measuring cellular respiration and for culture. Cellular mitochondrial O[2] consumption was determined as a function of time from the phosphorescence decay of the Pd [II] meso-tetra-[4-sulfonatophenyl]-tetrabenzoporphyrin. In sealed vials containing a foreskin specimen and glucose, O[2] concentration decreased linearly with time, confirming the zero-order kinetics of O[2] consumption by cytochrome oxidase. Cyanide inhibited O[2] consumption, confirming that the oxidation occurred mainly in the mitochondrial respiratory chain. The rate of foreskin respiration [mean +/- SD] was 0.074 +/- 0.02 microM O[2] min[-1] mg[-1] [n = 23]. The corresponding rate for fibroblast-rich cultures was 9.84 +/- 2.43 microM O[2] min[-1] per 10[7] cells [n = 15]. Fibroblast respiration was significantly lower in a male infant with dihydrolipoamide dehydrogenase gene mutations, but normalised with the addition of thiamine or carnitine. The foreskin and its fibroblast-rich culture are suitable for assessment of cellular respiration. However, the clinical utility of foreskin specimens to detect disorders of impaired cellular bioenergetics requires further investigation