Sanfilippo Found in Boy Despite Negative Urine Test, Calling Attention to Misdiagnosis Risk

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by Diogo Pinto |

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An atypical case of Sanfilippo syndrome, in which symptoms were evident but urine tests proved negative, highlights the heterogeneous nature of this condition and the likelihood of an initial misdiagnosis.

The study, “Delayed speech hyperactivity, and coarse facies: Does Sanfilippo syndrome come to mind?,” was published in the Journal of Pediatric Neurosciences.

Sanfilippo syndrome, also known as mucopolysaccharidosis type IIIA, is usually associated with progressive dementia, hyperactivity, and aggressive behavior.

But diagnosing this disease can be challenging, and frequently is associated with false negative results when using urine screening tests. As such, Sanfilippo syndrome remains as an underdiagnosed cause of developmental delay both in children and adults.

Ayse Kartal, a professor in the School of Medicine at Selçuk University in Turkey, reported a case of Sanfilippo syndrome diagnosed in a 7-year-old boy.

The child came to the pediatric neurology clinic with symptoms of hyperactivity, developmental delay, speech delay, and behavioral problems that had occurred for four years. The boy was the third child of healthy, unrelated Turkish parents.

No complications during pregnancy, and no medical records of speech delay or mental retardation in the family were registered.

However, a delay in the physical and psychological development of the boy was evident early on, and confirmed by a psychiatrist. The child began antipsychotic therapy with risperidone — a medication mainly used to treat schizophrenia, bipolar disorder, and irritability in people with autism.

A detailed examination revealed mild coarse facial features characteristic of many inborn disorders, with a slight depression in the nose and protuberances in the skull (skull bossing).

Neurological analysis reported mild speech disability and progressive hyperactivity. Alterations in the boy’s brain structure were observed using magnetic resonance imaging (MRI).

A possible diagnosis of Sanfilippo syndrome was suspected, but laboratory examination showed normal urine levels of glycosaminoglycans (GAGs), the most common test used to diagnose the disease. GAGs are a specific type of large sugar that in Sanfilippo syndrome accumulate within cells and tissues, damaging cells in multiple organs.

Blood analysis dictated the final Sanfilippo diagnosis, as no activity of the protein sulfamidase — responsible for breaking and clearing GAGs — was detected in the boy’s white blood cells.

The author  recommends screening for the disease in all patients with unexplained retardation in physical and psychological development, and progressive hyperactivity.

“The phenotypic spectrum of mucopolysaccharidosis III is less prominent than other MPS types and can result in a confusing clinical presentation; the diagnostic procedure can be challenging and often protracted,” Kartal concluded.

“Therefore, MPS III should be included in the differential diagnosis of developmental delay, especially in combination with coarse facies and previously described findings on MRI,” she added.