Galactosialidosis: A Report of Three Cases Diagnosed With a Founder Genetic Mutation in the Bahraini Population

Abstract

Galactosialidosis (GS, OMIM #256540) is a rare metabolic disorder resulting from mutations in the protective protein/cathepsin A (PPCA) or CTSA gene, which is characterized by malfunction of the lysosomal glycoprotein degradation and subsequent intra-lysosomal accumulation of sialyloligosaccharides and glycopeptides. It follows an autosomal recessive inheritance pattern. This systemic disease is characterized by typical clinical features such as short stature, coarse facial features, vertebral deformities, gastrointestinal manifestations, particularly hepatosplenomegaly, cardiac abnormalities, hearing loss, and macular cherry-red spots. GS is classified into three subtypes based on the age of onset and presenting symptoms. The three types include the early infantile (EI) form, which is the most severe; the late infantile form; and the juvenile/adult form. Here, we present three newly diagnosed cases of late-infantile GS in Bahraini patients, all sharing the same previously reported homozygous mutation in the CTSA gene (c.607C>A, p.Pro203Thr), confirmed by targeted mutation analysis. This mutation has been identified in nine Bahraini patients, reflecting a founder effect in the Bahraini population. All three patients presented with coarse facial features, short stature, and poor vision, alongside skeletal deformities. Patient 1 had significant bilateral hip osteoarthritis, while Patient 2. showed lumbar lordosis and extensive bilateral hip avascular necrosis. Patient 3 presented with thoracolumbar levoscoliosis and kyphoscoliosis. Additionally, in Patient 1 and Patient 2 cardiac manifestations were noted, including valvular heart disease. Patient 3 had mild left ventricular hypertrophy (LVH), aortic regurgitation, and mitral regurgitation, along with diffuse angiokeratomas. All patients are currently receiving supportive care and management. This case report highlights the importance of early diagnosis and multidisciplinary care of patients with GS.

Keywords: bahraini; founder mutation; galactosialidosis; lysosomal lipid storage disease; novel mutation.

Figure 1. Plain pelvic X-ray of Patient 1

Bilateral avascular necrosis of the hips, demonstrating flattening of the outer portion of both femoral heads, with more significant involvement observed in the right hip.

Figure 2. Family pedigree of two siblings with GS

Image credits: Zahra Alsahlawi, Zahraa J Alhadi. GS: galactosialidosis

Figure 3. Pelvic X-ray of Patient 2

Bilateral avascular necrosis of the hips.

Figure 4. Lateral X-ray view of the whole spine of Patient 2

Lumbar lordosis, characterized by an increased sacral base angle and forward translation of the thorax.

Figure 5. Clinical photograph showing the presenting signs in Patient 3

An 11-year-old child with (A) coarse facial features, (B) thoracolumbar kyphosis, and (C) angiokeratoma of the hand.

Figure 6. Sagittal T2 MRI of the brain in Patient 3

Enlarged sella turcica and diminished pituitary gland. The imaging correlates with impaired growth and suggests the presence of a partially empty sella turcica. MRI: magnetic resonance imaging

Figure 7. Whole spine CT scan showing a coronal view (A) and a 3D reconstruction (B)

The imaging reveals significant thoracolumbar levoscoliosis, with the maximum convexity observed at the T12-L1 level.