Weight Loss with Metachromatic Leukodystrophy (MLD) in South Africa

Navigating Nutrition, Antipsychotic Weight Gain & Adapted Exercise with ARSA Deficiency

By the WeightLossDiets.co.za Team | Updated June 2026

Metachromatic leukodystrophy (MLD) is a rare, progressive lysosomal storage disease caused by mutations in the ARSA gene, which encodes the enzyme arylsulfatase A. Without functional ARSA, sulfatides — a class of sulfated glycolipids — accumulate throughout the nervous system, destroying the myelin sheath and causing relentless neurological deterioration. MLD affects approximately 1 in 40,000 people globally; in South Africa, it is rarely diagnosed early due to limited metabolic screening capacity outside major academic centres.

MLD presents across three main age groups: late-infantile (onset before age 3, most common and most severe), juvenile (age 3–16), and adult-onset (age 16 and older, including middle age). The adult-onset form is particularly challenging to diagnose because its earliest symptoms — personality change, psychiatric disturbance, and cognitive decline — are frequently misattributed to schizophrenia or bipolar disorder. This guide focuses especially on the nutritional and weight management challenges faced by adult MLD patients in South Africa.

Why Weight Becomes a Problem in Adult MLD

Adult-onset MLD creates several distinct weight management challenges:

1. Antipsychotic Medication Weight Gain

Because adult MLD so often mimics psychiatric illness, many patients spend months or years on antipsychotic medications (olanzapine, quetiapine, clozapine, risperidone) before the correct diagnosis is made. These drugs are among the most potent causes of metabolic syndrome in medicine:

• Weight gain of 5–15 kg or more is common within the first year on atypical antipsychotics
• Insulin resistance and type 2 diabetes risk increase significantly
• Dyslipidaemia (raised triglycerides, lowered HDL cholesterol) is a direct drug effect
• Increased appetite and carbohydrate cravings are driven by histamine H1 and serotonin 5-HT2C receptor blockade

Even after an MLD diagnosis is established and psychiatric medications are reviewed, the metabolic consequences may persist and require active management.

2. Reduced Mobility as Disease Progresses

MLD causes progressive ataxia (unsteady gait), spasticity, and eventually loss of ambulation. Each step down in mobility reduces daily caloric expenditure, and without dietary adjustment, weight gain follows. Many adults with MLD become wheelchair-dependent within years of symptom onset.

3. Cognitive Decline Affecting Food Choices

As frontal lobe function deteriorates in MLD, executive function and impulse control diminish. This can lead to poor dietary choices, binge eating, and difficulty maintaining any structured eating plan. Carer involvement in meal planning and preparation becomes essential.

Dietary Approach for Adult MLD

The Mediterranean Pattern — Best Evidence for Neurological Disease

There is no sulfatide-restricted diet for MLD — unlike conditions such as phenylketonuria, you cannot reduce sulfatide accumulation by restricting dietary precursors, because sulfatides are synthesised in the body. Dietary management therefore focuses on overall metabolic and neurological health support:

• Omega-3 fatty acids: EPA and DHA (from oily fish — pilchards, sardines, salmon, mackerel) support myelin health and reduce neuroinflammation. Aim for 2–3 portions of oily fish per week. Canned pilchards in tomato sauce are an affordable SA staple.
• High fibre: Vegetables, legumes (lentils, sugar beans, chickpeas), oats, and fruit combat constipation (a common problem in reduced-mobility neurological disease) and improve insulin sensitivity
• Low glycaemic index carbohydrates: Particularly important if on antipsychotics that increase insulin resistance. Replace white bread, white rice, and sugary drinks with whole grains, sweet potato, and legumes.
• Limit saturated fat: Antipsychotic-induced dyslipidaemia is worsened by high saturated fat intake. Reduce fatty red meat, full-cream dairy in excess, and fried foods.
• Adequate protein: 1.2–1.5 g/kg/day to preserve muscle mass in the context of reduced activity and progressive neurological disease
• Rooibos tea: Naturally caffeine-free, rich in quercetin and aspalathin — antioxidants with anti-inflammatory properties. An excellent daily drink for MLD patients, especially those who should avoid caffeine due to seizure risk or sleep disturbance.

Managing Antipsychotic-Induced Hunger

If antipsychotic medications continue to be necessary (sometimes they are, even after MLD diagnosis, for behavioural symptoms), managing the associated appetite dysregulation requires practical strategies:

• Structured mealtimes: Set eating times (3 meals + 2 snacks) rather than grazing. Routine reduces impulsive eating.
• High-volume, low-calorie foods first: Start every meal with a large salad or vegetable soup. This blunts appetite before the calorie-dense components.
• Remove temptation: Keep high-calorie snacks out of the home. Stock the kitchen with pre-cut vegetables, fruit, and low-calorie snacks (biltong in controlled portions, rice cakes, plain popcorn).
• Carer-controlled portions: As cognitive decline progresses, a carer plating food in appropriate portions is the most effective intervention.
• Discuss medication switch: Some antipsychotics are more weight-neutral than others. Aripiprazole and ziprasidone have lower metabolic burden than olanzapine or clozapine. Discuss with the treating psychiatrist or neurologist whether a switch is clinically appropriate.

Exercise for Adult MLD — Slow the Decline

Physical activity is important for maintaining function, managing antipsychotic-related metabolic syndrome, and preserving quality of life in ambulatory adult MLD patients:

• Physiotherapy programme: A neuromuscular physiotherapist should design an individualised programme. Most SA academic hospital neurology departments have physiotherapy services; private neurological physiotherapists are available in major centres.
• Balance and coordination training: Ataxia creates significant fall risk. Targeted balance work (standing balance boards, tai chi adapted for ataxia) reduces fall frequency.
• Aquatherapy: Warm water reduces spasticity and fall risk while enabling meaningful exercise. Many private physiotherapy practices in SA have hydrotherapy pools.
• Seated aerobic exercise: Seated cycling (stationary bike or wheelchair ergometer), arm ergometry, and chair aerobics maintain cardiovascular fitness when ambulation becomes limited.
• Daily walking while possible: Even short walks (10–15 minutes twice daily) with appropriate assistive devices preserve ambulation longer. Use ankle-foot orthoses (AFOs) if prescribed.
• Avoid overheating and fatigue: Neurological function temporarily deteriorates with elevated body temperature (Uhthoff's phenomenon). Exercise in cool environments, especially during Gauteng and Western Cape summer heat.

Gene Therapy — Libmeldy and SA Access

Libmeldy (atidarsagene autotemcel), an ex-vivo haematopoietic stem cell gene therapy, was approved in the EU in 2020 for pre-symptomatic late-infantile and early juvenile MLD. It is not yet available in South Africa, and its benefit is restricted to patients treated before or at very early symptom onset — it does not reverse established disease. For most adult MLD patients in SA, treatment remains supportive. Clinical trial access is theoretically possible through international connections; contact the Hunter's Hope Foundation or MLD Foundation for guidance.

Managing Dysphagia in Late-Stage MLD

As MLD progresses, bulbar involvement causes dysphagia — a major safety and nutritional risk. Signs include:

• Coughing or choking on drinks
• Food sticking in the throat
• Wet or gurgling voice quality after eating
• Recurrent chest infections (possible aspiration pneumonia)

At first sign of dysphagia, refer to a speech-language therapist for a formal swallowing assessment. Modified texture diets and thickened fluids can maintain safe oral intake for longer. When oral intake becomes unsafe, PEG tube feeding preserves nutrition and quality of life.

Getting a Diagnosis in South Africa

Adult MLD is severely under-diagnosed in South Africa because psychiatric presentations are not routinely screened for lysosomal storage diseases:

• ARSA enzyme assay: Available through NHLS — a low ARSA enzyme level is diagnostic alongside clinical features and MRI evidence of white matter disease
• Urine sulfatides: Elevated urinary sulfatide excretion supports the diagnosis
• ARSA gene sequencing: PathCare, Lancet, and the Division of Human Genetics at Wits or Stellenbosch can perform this
• Brain MRI: Periventricular white matter changes in a "tiger stripe" or "leopard skin" pattern are characteristic of MLD
• If you or a family member has a young-onset psychiatric presentation with declining cognition and motor features, ask the neurologist or psychiatrist to consider an ARSA enzyme assay

South African Support Resources

• MLD Foundation: mldfoundation.org — international patient organisation with SA family contacts
• Hunter's Hope Foundation: huntershope.org — supports leukodystrophy families globally including SA
• ADSA (adsa.org.za): Find a registered dietitian with neurological nutrition experience
• Neurology at CHBAH, Groote Schuur, Tygerberg: Main tertiary referral centres for adult MLD in SA
• Division of Human Genetics, Wits/Stellenbosch: Genetic counselling and confirmatory testing

Key Takeaways

• Adult MLD is commonly misdiagnosed as schizophrenia or bipolar disorder — ask for ARSA enzyme testing in young adults with psychiatric plus neurological features
• Antipsychotic-induced weight gain is a major challenge — dietary structure, low-GI foods, and medication review are key interventions
• No dietary restriction of sulfatides is possible or needed — focus on Mediterranean anti-inflammatory eating
• Physiotherapy, aquatherapy, and balance training slow functional decline
• Involve a speech-language therapist at first sign of swallowing difficulty
• Libmeldy gene therapy exists but is not yet available in SA and only benefits pre-symptomatic patients
• Carers play an increasingly central role in meal planning and preparation as cognitive decline progresses

Sources: Biffi A (2017) "Metachromatic Leukodystrophy" GeneReviews; Gieselmann V & Krageloh-Mann I (2010) "Metachromatic Leukodystrophy — An Update", Neuropediatrics; NORD Rare Disease Database — Metachromatic Leukodystrophy; Libmeldy (atidarsagene autotemcel) EMA Summary of Product Characteristics 2020; SA NHLS diagnostic laboratory services; ADSA inherited metabolic disease nutrition guidelines.