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Background <p>Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is an autosomal recessive lysosomal storage disorder characterized by progressive central nervous system degeneration and behavioral abnormalities. Type A is caused by a deficiency of <i>SGSH</i>. This case report presents the first documented case of Sanfilippo syndrome type A (MPS IIIA) with a homozygous <i>SGSH</i> c.571G &gt; A mutation, associated with severe acute metabolic acidosis. Despite an extensive scoping review, no similar cases were found, highlighting the novelty of this report.</p> Case presentation <p>A 13-year-old girl presented with a 10-year history of global developmental regression and over 7 years of behavioral abnormalities, which had acutely worsened over the preceding three days. On admission, she was unconscious (Glasgow Coma Scale score (GCS): 10) and exhibited tachypnea. Arterial blood gas analysis revealed severe metabolic acidosis (pH 7.039, PaCO₂ 18.8 mmHg, HCO₃⁻ 5.1 mmol/L, base excess − 23.9 mmol/L, lactate 1.6 mmol/L), accompanied by hypernatremia, hyperchloremia, and markedly elevated creatine kinase and myoglobin levels. Lactate and ammonia concentrations were within normal limits. Neuroimaging (MRI) demonstrated cerebral atrophy with prominent sulci. Echocardiography showed mild valvular regurgitation, and skeletal survey suggested multiple bone dysplasias. Initially, central nervous system infection or metabolic encephalopathy was suspected. Following correction of acidosis, fluid resuscitation, and supportive care, she regained consciousness. Whole-exome sequencing identified a homozygous c.571G &gt; A (p. Gly191Arg) mutation in the <i>SGSH</i> gene, with both parents confirmed as heterozygous carriers at the same locus. Significantly reduced heparan N-sulfatase activity confirmed the diagnosis of mucopolysaccharidosis type IIIA (MPS IIIA).</p> Conclusions <p>Acute metabolic acidosis can occur in MPS IIIA, particularly during infection or physiological stress. Adolescents presenting with a long history of developmental regression and behavioral disturbances, accompanied by neuroimaging evidence of cerebral atrophy, should prompt strong consideration of MPS III. Combined genetic and enzymatic testing confirmed the diagnosis and guided multidisciplinary care. A comprehensive literature review revealed no previously reported cases of <i>SGSH</i> c.571G &gt; A mutation or MPS IIIA complicated by acute metabolic acidosis, making this the first documented case.</p>

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Sanfilippo syndrome type A with acute metabolic acidosis: a case report of the first documented SGSH c.571G > A homozygous mutation

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  • 发表日期：

    2026年2月26日

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  • Haiying Zou,
  • Li Yang,
  • Yao Qin,
  • Renlong Zhang

摘要

Background

Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is an autosomal recessive lysosomal storage disorder characterized by progressive central nervous system degeneration and behavioral abnormalities. Type A is caused by a deficiency of SGSH. This case report presents the first documented case of Sanfilippo syndrome type A (MPS IIIA) with a homozygous SGSH c.571G > A mutation, associated with severe acute metabolic acidosis. Despite an extensive scoping review, no similar cases were found, highlighting the novelty of this report.

Case presentation

A 13-year-old girl presented with a 10-year history of global developmental regression and over 7 years of behavioral abnormalities, which had acutely worsened over the preceding three days. On admission, she was unconscious (Glasgow Coma Scale score (GCS): 10) and exhibited tachypnea. Arterial blood gas analysis revealed severe metabolic acidosis (pH 7.039, PaCO₂ 18.8 mmHg, HCO₃⁻ 5.1 mmol/L, base excess − 23.9 mmol/L, lactate 1.6 mmol/L), accompanied by hypernatremia, hyperchloremia, and markedly elevated creatine kinase and myoglobin levels. Lactate and ammonia concentrations were within normal limits. Neuroimaging (MRI) demonstrated cerebral atrophy with prominent sulci. Echocardiography showed mild valvular regurgitation, and skeletal survey suggested multiple bone dysplasias. Initially, central nervous system infection or metabolic encephalopathy was suspected. Following correction of acidosis, fluid resuscitation, and supportive care, she regained consciousness. Whole-exome sequencing identified a homozygous c.571G > A (p. Gly191Arg) mutation in the SGSH gene, with both parents confirmed as heterozygous carriers at the same locus. Significantly reduced heparan N-sulfatase activity confirmed the diagnosis of mucopolysaccharidosis type IIIA (MPS IIIA).

Conclusions

Acute metabolic acidosis can occur in MPS IIIA, particularly during infection or physiological stress. Adolescents presenting with a long history of developmental regression and behavioral disturbances, accompanied by neuroimaging evidence of cerebral atrophy, should prompt strong consideration of MPS III. Combined genetic and enzymatic testing confirmed the diagnosis and guided multidisciplinary care. A comprehensive literature review revealed no previously reported cases of SGSH c.571G > A mutation or MPS IIIA complicated by acute metabolic acidosis, making this the first documented case.