Multiple epiphyseal dysplasia with early-onset diabetes mellitus (also known as Wolcott-Rallison syndrome) is a rare autosomal recessive disorder characterised by permanent neonatal diabetes mellitus, short stature, and hepatic dysfunction. Skeletal survey in patients show findings suggestive of spondyloepiphyseal dysplasia. These include platyspondyly with irregular upper and lower end-plates of vertebrate. The epiphyses in general appear small and flattened with fragmentation. There is usually generalized osteoporosis, narrow iliac wings, coaxa valga with hip dislocation and lateral displacement of the femoral epiphyses. The carpal centres of the hands are usually small and irregular, and the middle phalanges can be short. Some epiphyses appear dense or ivory-like.
Multiple epiphyseal dysplasia with early-onset diabetes mellitus results from mutations in the EIF2AK3 gene.
Marafie et al. (2004) described a male patient with Wolcott-Rallison syndrome born to healthy parents who were first cousins. Both were Kuwaitis from a large Bedouin tribe, the lineage of which extended back to the eastern coast of Saudi Arabia. Pedigree analysis revealed the presence of adult onset diabetes mellitus on both sides of the family, and early infant deaths, the cause of which could not be clarified. The child developed insulin dependent diabetes mellitus at the age of 2 months. At the ages of 10 months, 14 months and 2 1/2 years he developed gastroenteritis/upper respiratory tract infection with sever episodes of hepatitis with altered consciousness, jaundice and extremely high hepatic enzymes with hypoglycemia (a Reyes-like syndrome). The liver biopsy showed severe post-necrotic type bridging fibrosis with early nodular parenchymal hyperplasia, pale staining hepatocytes, and minimal inflammation, suggesting a metabolic disorder. At the age of 3 1/2 years he was diagnosed with hypothyroidism because of his short stature and dry skin. Clinical examination at the age of 7 years revealed a microbrachycephaly, a depressed nasal bridge, hypertelorism, a high arched palate, protruding ears with abnormal auricles, discolored and decayed teeth, a short neck with hyperpigmented dry skin. A skeletal survey revealed a generalized osteopenic texture, delayed bone age, multiple spondylo-epiphyseo-metaphyseal dysplasias. Marafie et al. (2004) expected that because of an increasing number of reports of Wolcott-Rallison syndrome in Arab children from the Arabian Peninsula there could be a quite large number of potential gene carriers in members of some highly inbred families from tribal origin in countries of the Gulf area.
Abdelrahman et al. (2000) reported a 3.5-year-old Saudi boy with Wolcott-Rallison syndrome [Abdelrahman S, Bin-Abbas B, Al-Ashwal A. Wolcott-Rallison syndrome in a Saudi infant. Curr Pediatr Res. 2000; 4:51-4].
Bin-Abbas et al. (2001) extensively revised the case of Abdelrahman et al. (2000). [Bin-Abbas B, Shabib S, Hainau B, Al-Ashwal A. Wolcott-Rallison syndrome: clinical, radiological and histological findings in a Saudi Child. Ann Saudi Med. 2001; 21(1-2):73-4].
One year later, Bin-Abbas et al. (2002) reported two sibs with features were suggestive of Wolcott-Rallison syndrome.
In 2004, Senee et al. conducted genetic analysis on the boy reported by Abdelrahman et al. (2000) and Bin-Abbas et al. (2001). They also analyzed his brother who was much recently diagnosed with the disease. Senee et al. (2004) also conducted genetic analysis on the patients described by Bin-Abbas et al. (2002). At the time of analysis, a third sib was born to the family and was diagnosed with diabetes at 2 weeks of age.
[See also: Kuwait > Marafie et al., 2004].
Nicolino et al. (1998) described a consanguineous family from Tunisia with Wolcott-Rallison syndrome. The family included three affected and one unaffected sibs with unaffected parents who were related as first cousins. In 2004, Senee et al. revised the three affected sibs described by Nicolino et al. (1998). They noted that all patients showed signs of exocrine pancreas dysfunction with fibrosis infiltrations in the pancreas biopsy of one of the patients. Neutropenia was also noted with frequent infections (bacterial, viral, and fungic).
[Nicolino PM, Dupin H, Macebeo V, Treppoz S, Chatelain PG. Wolcott-Rallison syndrome (diabetes mellitus and spondyloepiphyseal dysplasia): a plausible existence of a gene(s) important for the mutation of neonatal pancreatic beta cell function. Hormone Res. 1998; 50(suppl. 3):77 only.]