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Why does this 5-year-old boy have pebbled bumps covering his shoulder blades and hair growing all over his back? That's what Piyush Kumar, MD, of Madhubani Medical College and Hospital in India, and colleagues asked in their report published in .

The child's parents, who were in a non-consanguineous marriage, explained that the boy had been born with excessive hair growth, and about a year later, had developed raised skin-colored lesions on his back.

Examination of the patient's skin revealed multiple symmetrical, skin-colored papulonodules overlying the scapulae and back of his shoulders, which gave the skin a pebbled appearance. He also had generalized hypertrichosis.

Kumar and team noted that he was short for his age, with an unusually large head, coarse facial features with eyebrows that conjoined over the bridge of his nose, and an oversized tongue. His liver was also enlarged, and he had multiple joint contractures.

They learned that the child had experienced developmental delay and had some hearing loss. At the age of 2, he had also undergone surgery to repair umbilical and inguinal hernias. His family history provided no information to explain his condition.

The clinicians biopsied one of the lesions on his back, which revealed an extensive mucin deposit separating the collagen bundles throughout the dermis. A two-dimensional echocardiogram showed moderate mitral regurgitation.

Lab tests for enzymes revealed low levels of serum iduronate-2-sulphatase (IDS; 5.06 nmol/4 hours/mL; normal range 167-475 nmol/4 hours/mL) and normal total hexosaminidase levels (1,124 nmol/hour/mL; normal range 800-1,600 nmol/hour/mL).

Based on these characteristics, Kumar and team determined that the patient had mucopolysaccharidosis type 2, known as Hunter syndrome.

The team did not have access to molecular genetic testing to confirm diagnosis of this rare X-linked recessive disorder, which affects predominantly males. Hunter syndrome is a lysosomal storage disorder caused by deficient levels of IDS, "characterized by the accumulation of glycosaminoglycans (heparan sulfate and dermatan sulfate) within lysosomes and in extracellular spaces, leading to impaired cellular functions and inflammation," they wrote.

Over 600 variants have been observed in the IDS gene, which the authors said "is consistent with variable clinical features." Two main phenotypes have been noted: severe and attenuated. Disease tends to be of intermediate severity in many patients, they added.

Severe Hunter syndrome is notable for presenting early in childhood (age 2-4 years), Kumar and colleagues noted. It is marked by "hydrocephalus, prominent central nervous system (CNS) involvement and intellectual disability, behavioral changes, and decreased life expectancy."

In contrast, develops during later childhood or adolescence. It progresses more slowly, and is less likely to involve severe CNS and musculoskeletal disease; thus, patients are more likely to maintain normal cognitive function, and to have a longer life expectancy.

The pebbling of skin, which most often affects the scapular region, is a characteristic of Hunter syndrome, although not all patients are affected, the authors noted. However, it is not seen in other types of mucopolysaccharidosis. Other features include hypertrichosis and dermal hypermelanosis.

The of 82 patients with mucopolysaccharidosis type 2 noted the following clinical features that develop in patients between the ages of 2 and 8-9 years.

• Facial features (98%)
• Enlarged liver/spleen (88%)
• Joint stiffness (87%)
• Enlarged tongue (84%)
• Otitis (73%)
• Hernia (69%)
• Enlarged tonsils/adenoids (68%)
• Valvular disease (53%)
• Kyphosis/scoliosis (39%)
• Nasal obstruction (28%)

Of the cardiac manifestations, most began when patients were ages 6 to 8 years.

Diagnosis is made by estimating the presence of IDS in the serum or cells (such as fibroblasts and leukocytes), and genetic testing is used to confirm the diagnosis, Kumar and team noted.

Beyond supportive care, patients may be treated with hematopoietic stem cell transplant, gene therapy, and with recombinant IDS. The authors cautioned that the latter may improve some symptoms, but is not effective in managing CNS disease.

With treatment and supportive care, patients with mild Hunter syndrome can live into their 40s, they said. However, severe disease is associated with high mortality rates and earlier death; many patients die in the second decade of life, primarily due to lung and heart dysfunction.

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