Mucopolysaccharidoses (MPSs) are inherited metabolic disorders caused by a deficiency of lysosomal enzymes required for the degradation of mucopolysaccharides or glycosaminoglycans (GAGs). Depending on the deficient enzyme, MPSs can be classified to many types. MPS IV, or Morquio syndrome, occurs due to the deficiency of the enzymes N-acetyl-galactosamine-6-sulfatase and beta-galactosidase that are required for the degeneration of keratan sulfate (KS). Morquio syndrome is classified into two forms: (A and B). The prevalence is estimated to be 1:250,000 for Morquio syndrome A, while Morquio syndrome B occurs rarely.
In Morquio syndrome A, the deficiency of N-acetyl-galactosamine-6-sulfatase leads to the accumulation of mucopolysaccharides in the arteries, skeleton, eyes, joints, ears, skin, and/or teeth. Also, this accumulation can be found in the respiratory system, liver, spleen, central nervous system, blood, and bone marrow. Morquio syndrome A is characterized by abnormal skeletal development that includes growth retardation, a prominent lower face, an abnormally short neck, knock knees or genu valgum, flat feet, kyphoscoliosis, abnormal development of the growing ends of the long bones (epiphyses), joint hyperlaxity, and/or a prominent breast bone (pectus carinatum). Skeletal deformities will lead also to growth arrest at around eight years. Hearing loss, weakness of the legs, nervous complications, and/or additional abnormalities may also occur. On the other hand, patients with Morquio syndrome A usually have normal intelligence.
The disorder is diagnosed during the second year of life, after walking acquisition, and skeletal deformities become more apparent with growing. Treatment is symptomatic and recombinant enzyme therapy is used recently.
Aboul Nasr and Fateen (2004) performed prenatal diagnosis of mucopolysaccharidosis type IV (Morquio) in a pregnant female. Chorionic villus sampling (CVS) was done at 11-12 weeks gestational age to perform the specific enzyme assay fluorimetrically which was developed during the study. The pregnancy demonstrated a normal fetus.
Joshi et al. (2002) carried out a retrospective analysis of all patients born with inborn errors of metabolism in Oman between June 1998 and December 2000. Among 82 patients, only one child was diagnosed with MPS type 4 [CTGA Database Editor's note: Computed annual incidence rate is 0.8/100,000].
Qubbaj et al. (2008) performed preimplantation genetic diagnosis for a couple with three children affected with Morquio disease, having homozygous W159C mutation in GALNS gene. The couple were first cousins, and had a 14-year-old affected daughter and twin affected sisters. Both twins presented with dysmorphic features, spondyloepiphyseal abnormalities, short stature, and cardiac valvular involvement. One of the twins died at the age of 4-years due to chest infection. Performing ovarian stimulation, oocyte retrieval, intracytoplasmic sperm injection procedure, embryo biopsy, cell lysis, and multiple displacement amplification, three embryos out of seven were genotypically normal and two were transferred back to the mother on day 4. Pregnancy ensued and a carrier healthy male infant was delivered. The misdiagnosis was explained by allele dropout (ADO) of the mutant allele in embryo 3.
Moammar et al. (2010) reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Affected patients were evaluated based on clinical manifestations or family history of similar illness and/or unexplained neonatal deaths. Almost all patients were born to consanguineous parents. Lysosomal storage disorders were the most diagnosed category of IEM in this cohort (74 out of 248 cases, 30%). Among them, six cases from four families were found to have MPSIV, with an estimated incidence of 4 per 100,000 live births. The authors concluded that data obtained from this study underestimate the true figures of various IEM in the region. Therefore, there is an urgent need for centralized newborn screening program that utilizes tandem mass spectrometry, and offers genetic counseling for these families.
Laradi et al. (2006) described two novel GALNS mutations in six severe MPS IVA patients (two males and four females) from four unrelated Tunisian families. The age of the patients ranged from seven to 15 years and one patient died at seven years. Their height did not exceed one meter. They presented marked growth retardation, spinal deformity, chest deformity, genu valgum, and corneal opacities. Hepatomegaly was observed in two patients, bilateral deafness in one, and spastic paraplegia in two patients. The GALNS enzymatic assay was performed showing that all patients had GALNS enzymatic activity below 1% of normal. Five patients were homoallelic for a novel splice site mutation (IVS1+1G-to-A) of intron 1. This splice site mutation presumably caused exon skipping, loss of exon 2, and an aberrant polypeptide which was misfolded and degraded and that would be consistent with the severe enzyme deficiency and phenotype of the five patients. The other patient was homozygous for a G-to-C transversion in exon 2 predicting a glycine to arginine missense mutation (G66R). In addition, three intragenic polymorphisms in exons 7 (H236H), 13 (E477E), and 12 (P420P) were identified in the MPS IVA alleles. The (IVS1+1G-to-A) splice site mutation was detected in three families that shared a common GALNS haplotype, suggesting that the mutation was inherited from a common ancestor. Laradi et al. (2006) suggested that the incidence of MPS IVA in Tunisia is higher than other communities (2.8:100,000).