Weight Loss with Mucopolysaccharidosis (MPS) in South Africa

A group of lysosomal storage disorders where glycosaminoglycan accumulation reshapes bones, airways, heart, and mobility — making weight management a whole-body challenge

Mucopolysaccharidoses (MPS) are a family of rare inherited lysosomal storage disorders in which specific enzymes needed to break down glycosaminoglycans (GAGs) are deficient or absent. Without these enzymes, GAGs such as heparan sulphate, dermatan sulphate, and keratan sulphate accumulate progressively inside lysosomes throughout the body, causing multi-system damage that worsens over time.

There are seven major MPS types (I through IX), each caused by a different enzyme deficiency. The most widely known are MPS I (Hurler/Hurler-Scheie/Scheie syndromes, due to alpha-L-iduronidase deficiency), MPS II (Hunter syndrome, iduronate-2-sulphatase deficiency — X-linked, males only), MPS III (Sanfilippo, CNS predominant), MPS IV (Morquio, skeletal), and MPS VI (Maroteaux-Lamy). All share progressive GAG accumulation, but the tissues most affected differ by type.

Weight management in MPS is shaped by profound physical changes — skeletal dysplasia, joint contractures, heart valve disease, obstructive sleep apnoea, and restricted mobility — alongside the metabolic effects of enzyme replacement therapy (ERT) and, in severe cases, haematopoietic stem cell transplantation (HSCT). This article explains the landscape and what realistic, safe weight management looks like.

How MPS Affects Body Weight and Composition

1. Skeletal Dysplasia and Short Stature

In many MPS types (especially MPS I, II, IV, and VI), progressive dysostosis multiplex leads to short stature, kyphosis, scoliosis, and joint stiffness. Standard BMI thresholds based on height are misleading in these patients — someone may appear "overweight" by BMI despite having normal fat mass for their frame. Clinicians prefer arm-span measurements, skin-fold assessments, or DXA body composition scans.

2. Joint Contractures and Restricted Mobility

GAG accumulation in joint capsules, tendons, and soft tissue progressively limits range of motion — especially in hips, knees, shoulders, and hands. In adults with attenuated MPS (Scheie, attenuated Hunter, Maroteaux-Lamy), reduced mobility directly cuts calorie expenditure, promoting fat accumulation even at moderate intake. This is the primary driver of overweight in ambulatory adult MPS patients.

3. Obstructive Sleep Apnoea (OSA)

GAG accumulation in the pharynx, tongue, tonsils, and adenoids causes severe airway narrowing. OSA is present in the majority of MPS patients and disrupts sleep architecture, promoting insulin resistance, leptin resistance, and daytime fatigue that further reduces activity. OSA treatment (CPAP, BiPAP, or surgical airway intervention) is a prerequisite for meaningful weight management — untreated OSA makes weight loss nearly impossible.

4. Cardiac Involvement

Heart valve disease (mitral and aortic regurgitation) is common in MPS I, II, and VI. Reduced cardiac output limits exercise capacity. Vigorous aerobic exercise is contraindicated until cardiology has assessed valve function and cleared the patient.

5. Cervical Spine Instability

In MPS IV (Morquio) and some MPS I patients, odontoid hypoplasia and ligament laxity create atlanto-axial instability — the top two vertebrae can sublux under stress, risking spinal cord injury. This means many conventional exercises (contact sports, heavy weightlifting, rapid neck movements) are absolutely contraindicated. Exercise programmes must be designed with this in mind.

Enzyme Replacement Therapy (ERT) and Weight

ERT is the primary disease-modifying treatment available for MPS I (laronidase/Aldurazyme), MPS II (idursulfase/Elaprase), MPS IVA (elosulfase alfa/Vimizim), MPS VI (galsulfase/Naglazyme), and MPS VII (vestronidase alfa/Mepsevii). ERT reduces urinary GAG excretion, preserves cardiac function, improves respiratory capacity, and in some types modestly improves joint mobility. It does not cross the blood-brain barrier and does not reverse existing neurological damage.

ERT is administered by intravenous infusion weekly or fortnightly at a hospital or infusion centre. Infusion reactions are common, especially early in treatment, and pre-medication with antihistamines and corticosteroids is routine. Repeated steroid pre-medication can contribute to weight gain over time — discuss this with your treating team if weight is a concern.

For severe MPS I (Hurler syndrome) in young children, haematopoietic stem cell transplantation (HSCT) is the treatment of choice to preserve cognitive function. Post-HSCT immunosuppression and the metabolic stress of transplantation both influence nutritional status in the months following the procedure.

Dietary Approach for Adults with Attenuated MPS

Adults with attenuated MPS who are ambulatory and gaining weight due to reduced mobility benefit most from dietary modification:

• Moderate calorie deficit: 300-400 kcal/day below estimated needs — no aggressive restriction. Target 0.25-0.5 kg/week loss.
• High protein to preserve muscle: 1.2-1.6 g protein/kg body weight per day. Sources: eggs, tinned fish, chicken, cottage cheese, legumes, Greek yoghurt.
• Anti-inflammatory focus: Mediterranean-style eating — olive oil, oily fish, vegetables, legumes, limited processed food — reduces systemic inflammation driven by GAG accumulation.
• Fibre for gut health: GAG accumulation can affect gut motility in some patients. High-fibre vegetables, legumes, and ground flaxseed support digestive regularity. Rooibos tea is a pleasant, caffeine-free, antioxidant-rich addition.
• Calcium and vitamin D: Skeletal dysplasia and limited sun exposure mean these should be checked and supplemented as needed.
• Cut ultra-processed foods first: Chips, fast food, sugary drinks, and commercial biscuits are calorie-dense with low satiety.

Exercise That Works Around MPS Restrictions

All exercise plans should be designed with a physiotherapist experienced in connective tissue and skeletal dysplasia conditions. The goal is to preserve existing mobility, improve cardiovascular health within cardiac limits, and increase calorie expenditure — not to push performance.

Treat Sleep Apnoea First

If OSA is present and untreated, weight loss efforts will largely fail. OSA causes hormonal disruption — elevated ghrelin, suppressed leptin, cortisol dysregulation — that drives hunger, sugar cravings, and fat storage. CPAP or BiPAP compliance must be established first. Many patients find that treating OSA alone results in 2-5% spontaneous weight reduction over 6 months due to hormonal normalisation, before any dietary changes are made.

Realistic Weight Goals in MPS

In children, the goal is usually maintaining healthy growth trajectories rather than weight loss. In adults with attenuated disease gaining weight from immobility, losing 5-10% of body weight over 12 months is a realistic and clinically meaningful target — it reduces joint load, improves OSA severity, lowers cardiovascular risk, and improves energy levels.

Do not chase "normal BMI" as the target — for patients with short stature and altered body composition, this is often neither achievable nor appropriate. Focus on functional outcomes: improved mobility, better sleep quality, reduced joint pain, and stable cardiac parameters.

Accessing Care in South Africa

MPS is managed at specialist metabolic centres including Red Cross War Memorial Children's Hospital (Cape Town), Steve Biko Academic Hospital and Wits Donald Gordon Medical Centre (Johannesburg), and Inkosi Albert Luthuli Central Hospital (Durban). ERT access is via the Departments of Health and requires specialist motivation. The South African metabolic dietitian network can be accessed through your treating hospital.