Zeliweger Syndrome in Saudi Arabia and Its Distinct Features

Abstract

Clinical and laboratory findings of Zellweger syndrome (ZS) patients diagnosed at King Faisal Specialist Hospital and Research Center (KFSH & RC), Riyadh, Saudi Arabia over a period of 10 years are presented in this report. Eleven patients (nine females and two males) from 2 to 4 months old were referred to KFSH & RC for evaluation of hypotonia, seizures, and dysmorphic features. The common clinical findings included high forehead, large fontanelle, shallow orbit ridges, micrognathia, upslanting palebral fissures, epicanthal folds, severe hypotonia, hyporeflexia, pigmentary retinopathy, optic nerve atrophy, complete or partial agenesis of corpus callusum, and failure to thrive. We did not observe any Brushfield spots, any renal and brain cysts, or adrenal insufficiency. Some unique clinical findings were the presence of gallstones, club feet, or bilateral knee or hip dislocation in some patients. All patients had markedly elevated plasma levels of very long chain fatty acids (VLCFA). Electron microscopy performed on liver biopsies of two patients revealed absence of peroxisomes. Biochemical studies of dermal fibroblasts from three patients showed deficient beta-oxidation of lignoceric acid and dihydroxyacetone phosphate acyltransferase (DHAPATase) activity. The tribal living in Saudi Arabia and our observation that 10 of the 11 parents in this study were first-degree relatives and, except for families 1 and 3, each family had at least another baby who died of the same disease. This suggests that the incidence of ZS in Saudi Arabia may actually be higher than our experience at KFSH & RC.

Cranial Ultrasound in Metabolic Disorders Presenting in the Neonatal Period: Characteristic Features and Comparison with MR Imaging

“…10,13,14,17,26 Most infants with peroxisomal biogenesis disorders had multiple GLCs and ventricular dilation, often with abnormal peri-Sylvian cortical folding and LSV. These findings were apparent on cUS and consistent with case reports, 15,19,24 contributing to an early diagnosis. To our knowledge, no cUS findings have been described previously in neonatal adrenoleukodystrophy.…”

“…[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] cUS has the advantage that it is readily available on neonatal units when infants are admitted. We have shown in a large cohort of neonates with diagnosed metabolic disorders that cUS detects many abnormalities that support a clinical diagnosis, detects structural abnormalities that lead to further investigations, or depicts ongoing injurious or metabolic processes.…”

“…[5][6][7] Metabolic disorders can be difficult to diagnose, and recognition of characteristic neuroimaging features is very helpful in the diagnostic process. 8,9 Structural brain abnormalities and more acute changes detected on cUS scan in metabolic disorders have been described in individual case reports, [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] but there is no large study systematically reviewing these imaging findings and their accuracy or comparing them with MR imaging. The aim of this study, therefore, was primarily to investigate the role and range of abnormalities seen on cUS examination in a wide range of metabolic disorders that present during the neonatal period; a secondary aim, when possible, was to address the question of whether brain MR imaging is more informative by comparing cUS to MR imaging findings.…”

Oral manifestations and dental management of a child with Zellweger syndrome

“…Patients with ZS are characterized mainly by their typical craniofacial dysmorphism and neurological abnormalities . The craniofacial dysmorphic features include a high forehead, large fontanels, hypoplastic supraorbital ridges, epicanthal folds, flat and broad nasal bridge, external ear deformities, micrognathia, and high arched palate . The neurological abnormalities include severe hypotonia, abnormal Moro reflex, hypo‐ or a‐reflexia, epileptic seizures, and psychomotor retardation .…”

“…The craniofacial dysmorphic features include a high forehead, large fontanels, hypoplastic supraorbital ridges, epicanthal folds, flat and broad nasal bridge, external ear deformities, micrognathia, and high arched palate . The neurological abnormalities include severe hypotonia, abnormal Moro reflex, hypo‐ or a‐reflexia, epileptic seizures, and psychomotor retardation . Other organs are usually affected including the eye (brush‐field spots, corneal clouding, cataracts, glaucoma, optic nerve dysplasia, and retinal anomalies), the liver (hepatomegaly, fibrosis, cholestasis), and the kidney (cysts) .…”