# Alkaline Phosphatase and Infantile GM1 Gangliosidosis: A Simple Biomarker for a Complex Disease?

## TL;DR

The paper discusses how persistent hyperphosphatasemia in infants, along with other subtle signs like limb edema, can be an early indicator of infantile GM1 gangliosidosis, a severe genetic disorder.

## Contribution

The study highlights hyperphosphatasemia as a potential early nonspecific biomarker for diagnosing infantile GM1 gangliosidosis in the absence of classic clinical features.

## Key findings

- A case of infantile GM1 gangliosidosis was diagnosed at 3 months based on persistent hyperphosphatasemia and limb edema.
- Early biochemical markers like hyperphosphatasemia may allow timely diagnosis and genetic testing for GLB1 mutations.
- Dysplastic mitral valve and urinary oligosaccharide profile confirmed the diagnosis in the absence of typical LSD signs.

## Abstract

GM1 gangliosidosis is a lysosomal storage disease (LSD) caused by β‐galactosidase deficiency, characterized by the accumulation of gangliosides in various tissues. Among different GM1 forms (infantile form, late‐infantile and juvenile form, and late‐onset form), the infantile form is the most severe: despite an early clinical onset with rapid neurodegeneration, coarse face, abdominal visceromegaly and skeletal abnormalities, the diagnosis is usually delayed, given the lack of recognized early disease‐specific markers. We report the case of a newborn presenting with mild edema of hands and feet, mild transient hypoalbuminemia and isolated hyperphosphatasemia at three weeks of life. The first cardiological evaluation showed mild mitral regurgitation. Despite the absence of neurological symptoms, organomegaly, or a coarse face, the turgid consistency of the limbs, together with mitral regurgitation and persistent hyperphosphatasemia, led to multiorgan investigations with discovery of bilateral cherry‐red spots and a beak‐shaped lumbar vertebra. The cardiological follow‐up revealed a dysplastic mitral valve. In the suspicion of a lysosomal disease, biochemical investigations were planned. An altered profile of urinary oligosaccharides, along with low β‐galactosidase activity in leukocytes, led to the diagnosis of infantile GM1 gangliosidosis at 3 months of age. The GLB1 gene analysis confirmed the diagnosis. Genetic testing for GLB1 should be considered in cases of persistent hyperphosphatemia, especially if it is associated with any other clinical indicator of GM1, such as limb edema.

Clinicians should consider GM1 gangliosidosis in newborns and infants with unexplained hyperphosphatasemia and any other clinical indicator of GM1, such as edema of the limbs, even in the absence of other macroscopic clinical signs of this disease.Identification of early, albeit nonspecific, biochemical markers may enable timely diagnostic evaluation, including GLB1 genetic testing, and facilitate appropriate patient management.

Clinicians should consider GM1 gangliosidosis in newborns and infants with unexplained hyperphosphatasemia and any other clinical indicator of GM1, such as edema of the limbs, even in the absence of other macroscopic clinical signs of this disease.

Identification of early, albeit nonspecific, biochemical markers may enable timely diagnostic evaluation, including GLB1 genetic testing, and facilitate appropriate patient management.