Aminoacidopathies and organic acidurias in Tunisia: a retrospective survey over 23 years

Inborn errors of metabolism are neglected in developing countries because they are not as common as infectious and nutritional disorders. In Tunisia, no information is available on the incidence and epidemiological features of these inherited metabolic diseases. To precise the profile of aminoacidopathies other than phenylketonuria and organic acidurias and to estimate their incidences in Tunisia. Between 1987 and 2009, our laboratory received 13171 requests for analysis of patients with symptoms suggestive of inborn errors of metabolism. For these cases, ion exchange chromatography of free amino acids was performed on amino acids analyser. Urinary organic acids profiles were determined by gas chromatography-mass spectrometry. Abnormal cases were 370 [2.8%], divided into 212 cases of aminoacidopathies [57.3%] and 158 cases of organic acidurias [42.7%]. The most frequent aminoacidopathies, were maple syrup disease [32.5%], tyrosinemia type I [28.8%] and nonketotic hyperglycinemia [16%]. Methylmalonic aciduria [33.5%], propionic aciduria [18.4%] and 2-hyrdoxy glutaric aciduria [10.8%] were the most frequent organic acidurias. The incidences were calculated using the Hardy-Weinberg formula and were estimated at 1/13716 for maple syrup disease, 1/14804 for tyrosinemia type I, 1/16144 for methylmalonic aciduria and 1/23176 for propionic aciduria. Aminoacidopathies and organic acidurias turned out to be highly frequent in Tunisia, mainly because of a high rate of consanguinity. We believe that they are underestimated. To improve their diagnosis, it is necessary to have available sophisticated equipment which would allow early treatment of patients

[ novel mutation in PEX 26 gene in Zellweger syndrome: a case report]

Zellweger syndrome is the most severe phenotype of the peroxisome biogenesis disorders caused by mutations in PEX genes. PEX 1, 6 and 26 genes are most frequently implicated. Clinical phenotype can't predict the mutated gene. To report a novel mutation in the PEX 26 gene in infant with typical Zellweger syndrome. The infant was the second child to consanguineous parents; the 1st child was dead with neonatal hypotonia. At two month of age, we noted a severe hypotonia and growth failure, characteristic facial dysmorphic features and cryptorchidism. Sensorial investigations showed optic atrophy. Cerebral tomography revealed white matter hypodensity. Radiological examination revealed calcific stippling of the patellas. The clinical diagnosis was supported by measurement of plasma very-long-chain fatty acids, with elevated C24:0/C22:0, C26:0/C22:0 ratios and decreased docosanoic acid peak. The diagnosis was confirmed by dosage of DHAP-AT activity in fibroblasts which was very low. Ultrastructural examinations showed the presence of peroxisomal ghosts. Genetic analysis demonstrated a new mutation in PEX 26 gene.The death occurred at the age of 8 months of refractor epilepsy and apneas. The poor prognosis of ZS incites paediatricians to consider this disorder in etiological investigations of precocious hypotonia. Biochemical diagnosis, available in Tunisia, offers opportunity of prenatal diagnosis in affected families