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Year : 2016  |  Volume : 11  |  Issue : 3  |  Page : 282-284

Delayed speech, hyperactivity, and coarse facies: Does Sanfilippo syndrome come to mind?

Department of Pediatric Neurology, School of Medicine, Selçuk University, Konya, Turkey

Date of Web Publication3-Nov-2016

Correspondence Address:
Ayşe Kartal
Department of Pediatric Neurology, School of Medicine, Selcuk University, Konya
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1817-1745.193378

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Mucopolysaccharidosis Type IIIA (MPS IIIA) or Sanfilippo-A syndrome is caused by a deficiency in lysosomal a-heparan N-sulfatase. Its clinical manifestations include progressive dementia, hyperactivity, and aggressive behavior. Unlike other mucopolysaccharide disorders, the diagnosis of MPS IIIA is challenging in both adults and children. This diagnostic challenge has been associated with the high incidence of false negative results encountered on urinary screening tests. We herein describe Sanfilippo-A syndrome in a pediatric patient who presented with progressive hyperactivity, delayed language, and developmental delay and a negative urine screening test. We emphasized that these findings may serve as possible initial presentations of MPS IIIA; therefore, screening for MPS should be done in all patients with unexplained psychomotor retardation and progressive hyperactivity.

Keywords: Developmental delay, hyperactivity, mucopolysaccharidosis, Sanfilippo

How to cite this article:
Kartal A. Delayed speech, hyperactivity, and coarse facies: Does Sanfilippo syndrome come to mind?. J Pediatr Neurosci 2016;11:282-4

How to cite this URL:
Kartal A. Delayed speech, hyperactivity, and coarse facies: Does Sanfilippo syndrome come to mind?. J Pediatr Neurosci [serial online] 2016 [cited 2021 Apr 21];11:282-4. Available from: https://www.pediatricneurosciences.com/text.asp?2016/11/3/282/193378

   Introduction Top

Sanfilippo syndrome (mucopolysaccharidosis Type IIIA [MPS IIIA]) is a progressive disorder, in which patients are characterized by progressive neurocognitive decline, behavioral difficulties together with mild somatic disease.[1] Unlike other mucopolysaccharide disorders, the patients have few somatic features or skeletal changes and a high incidence of false negative results on urinary screening tests; hence, it remains underdiagnosed as a cause of developmental delay both in children and adults.[2]

We report a rare case of unexpected MPS IIIA which was diagnosed in a pediatric patient. Here, we emphasize the importance of physical examination and as part of the diagnostic process.

   Case Report Top

A 7-year-old boy was referred to our pediatric neurology clinic for hyperactivity, speech delay, and behavioral problems that had lasted for 4 years. The patient is the third of healthy unrelated Turkish parents. He was born at term after uneventful gestational delivery. Furthermore, there was no family history of speech delay or mental retardation. He walked at 2 years and spoke his first words at 3 years. Later on, a more general retardation in psychomotor development with restlessness and impulsivity with hyperactivity became evident, for which he was referred to a child psychiatrist. On evaluation, he was considered to have attention deficit hyperactivity disorder. The treatment with antipsychotic drugs (risperidone) was started; however, improvements in neurologic status were not observed after 6 months. He also had a history of recurrent upper respiratory tract infections.

On physical examination, he had normal anthropometry and head circumference, mildly coarse facial features, slightly depressed nasal bridge, frontal bossing, and stocky hands with short fingers [Figure 1]. Organomegaly was not present.
Figure 1: Dysmorphic features of our patient. Facial dysmorphism (coarse facial features, the slightly depressed nasal bridge, and frontal bossing)

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Neurological examination showed normal tone, power, and deep tendon reflexes with bilateral flexor plantar response. He was awake, alert, and anxious. He had a mild language disability.

Laboratory investigations showed normal values of blood counts, chemistry, electrolytes. Urine organic acids, tandem mass, plasma lactate, pyruvate, thyroid function tests, and karyotype, and fragile X tests were normal.

In light of these findings, such as coarse facies and progressive hyperactivity, the diagnostic possibility of MPS was suspected, but subsequent laboratory examination revealed normal urine glycosaminoglycans (GAGs). Skeletal survey was not suggestive of the characteristic dysostosis complex. Magnetic resonance imaging (MRI) of the brain showed J-shaped sella turcica, mild widening of the lateral ventricles with thinning of the corpus callosum and small perivascular spaces in the bilateral parietal regions. In addition, there were cysts (isointense to cerebrospinal fluid and therefore likely representing dilated perivascular spaces) within the body of the corpus callosum [Figure 2].
Figure 2: Magnetic resonance imaging of the brain: Sagittal T2-weighted images of the patient demonstrating, thinning of the corpus callosum, and dilated perivascular spaces within the body of the corpus callosum (arrows), J-shaped sella turcica (arrows), and enlarged subarachnoid area

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Enzyme analysis for MPS IIIA showed null activity of the enzyme sulfamidase activity in leukocytes (normal range 3.2–20.4 nmol/17 h), confirming the diagnosis. He was started on rehabilitation and behavior therapy for hyperactivity.

   Discussion Top

MPS III or Sanfilippo syndrome is an autosomal recessive metabolic disorder characterized by accumulation of the GAG heparan sulfate. MPS III is classified into four different subtypes including A, B, C, and D based on the deficiency of a specific enzyme in the degradation of heparan sulfate. Type IIIA is the most common subtype.[1] The hallmarks of the disease are progressive mental deterioration, speech delay, and behavioral problems.

Early development of MPS III is typically normal, and developmental delay, behavioral problems, or a combination of these symptoms are usually the first symptoms.[3] The clinical course of MPS III is divided into three phases.[2],[4] In the first phase which usually starts between 1 and 4 years of age, a slowing mental development becomes apparent. The second phase is followed by behavior problems which usually begin at ages 4 or 5 and consist of temper tantrum, aggressive behavior, and extreme restlessness. The third phase generally starts at the end of the first decade which is associated with severe dementia, decline motor functions. Finally, death usually occurs in the third decade.

In our patient, the presence of hyperactivity and speech delay was the focus of the initial investigative workup through a child psychiatry clinic. The patient may consider being the second phase due to clinical features.

In contrast to other MPS somatic symptoms, MPS III is relatively mild and can be easily missed although these may be more obvious in Phase 1 or early Phase 2.[5] In our patient, there were coarse facial features that attracted the first thing, our attention.

Some radiological findings may provide a key diagnostic clue for MPS.[6] The most common radiological findings are described as dysostosis multiplex.[7] This comprises enlarged skulls thoracolumbar kyphosis, abnormally shaped vertebrae and ribs, spatulate ribs, hypoplastic epiphyses, thickened diaphyses, and bullet-shaped metacarpals. Furthermore, ventricular dilatation and enlargement of subarachnoid spaces, thin corpus callosum, enlarged perivascular spaces are also considered common neuroimaging findings in MPS III.[8],[9] MRI findings encountered in our case were in accordance with those reported in literature, however, X-ray findings in our patient did not show dysostosis.

Determination of increased urinary GAG levels are useful in the initial assessment for MPS, but these tests can give false negative results as in our patient.[10] Thus, the diagnosis of MPS should not be excluded on the basis of a single GAG test.

   Conclusion Top

The phenotypic spectrum of MPS III is less prominent than other MPS types and can result in a confusing clinical presentation; the diagnostic process can be challenging and often protracted. 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.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Valstar MJ, Ruijter GJ, van Diggelen OP, Poorthuis BJ, Wijburg FA. Sanfilippo syndrome: A mini-review. J Inherit Metab Dis 2008;31:240-52.  Back to cited text no. 1
Wijburg FA, Wegrzyn G, Burton BK, Tylki-Szymanska A. Mucopolysaccharidosis type III (Sanfilippo syndrome) and misdiagnosis of idiopathic developmental delay, attention deficit/hyperactivity disorder or autism spectrum disorder. Acta Paediatr 2013;102:462-70.  Back to cited text no. 2
Meyer A, Kossow K, Gal A, Mühlhausen C, Ullrich K, Braulke T, et al. Scoring evaluation of the natural course of mucopolysaccharidosis type IIIA (Sanfilippo syndrome type A). Pediatrics 2007;120:e1255-61.  Back to cited text no. 3
Valstar MJ, Marchal JP, Grootenhuis M, Colland V, Wijburg FA. Cognitive development in patients with mucopolysaccharidosis type III (Sanfilippo syndrome). Orphanet J Rare Dis 2011;6:43.  Back to cited text no. 4
Moog U, van Mierlo I, van Schrojenstein Lantman-de Valk HM, Spaapen L, Maaskant MA, Curfs LM. Is Sanfilippo type B in your mind when you see adults with mental retardation and behavioral problems? Am J Med Genet C Semin Med Genet 2007;145:293-301.  Back to cited text no. 5
Palmucci S, Attinà G, Lanza ML, Belfiore G, Cappello G, Foti PV, et al. Imaging findings of mucopolysaccharidoses: A pictorial review. Insights Imaging 2013;4:443-59.  Back to cited text no. 6
Lachman R, Martin KW, Castro S, Basto MA, Adams A, Teles EL. Radiologic and neuroradiologic findings in the mucopolysaccharidoses. J Pediatr Rehabil Med 2010;3:109-18.  Back to cited text no. 7
Zafeiriou DI, Batzios SP. Brain and spinal MR imaging findings in mucopolysaccharidoses: A review. AJNR Am J Neuroradiol 2013;34:5-13.  Back to cited text no. 8
Calleja Gero ML, González Gutiérrez-Solana L, López Marín L, López Pino MA, Fournier Del Castillo C, Duat Rodríguez A. Neuroimaging findings in patient series with mucopolysaccharidosis. Neurologia 2012;27:407-13.  Back to cited text no. 9
Lehman TJ, Miller N, Norquist B, Underhill L, Keutzer J. Diagnosis of the mucopolysaccharidoses. Rheumatology (Oxford) 2011;50 Suppl 5:v41-8.  Back to cited text no. 10


  [Figure 1], [Figure 2]


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