Weight Management with Smith-Lemli-Opitz Syndrome in South Africa
Smith-Lemli-Opitz Syndrome (SLOS) is one of the most counter-intuitive conditions in medicine — it is a cholesterol deficiency disorder in which the body cannot make enough cholesterol and accumulates a toxic precursor instead. In almost every other context, dietary cholesterol is something we are told to limit. In SLOS, adequate dietary cholesterol intake can be life-changing. This guide explains the unique nutritional needs of SLOS and how to manage weight and health in a South African context.
What Is Smith-Lemli-Opitz Syndrome?
SLOS is an autosomal recessive metabolic disorder caused by mutations in the DHCR7 gene, which encodes the enzyme 7-dehydrocholesterol reductase (DHCR7). This enzyme is responsible for the final step in cholesterol biosynthesis. When it is absent or deficient, the body:
- Fails to produce adequate cholesterol — critical for cell membranes, myelin sheaths, steroid hormones, bile acids and brain development
- Accumulates toxic 7-dehydrocholesterol (7-DHC) — which damages cells, particularly neurons
SLOS occurs in approximately 1 in 20 000–60 000 births, though the carrier frequency is higher than this suggests. In South Africa, it is likely under-diagnosed due to limited newborn screening.
Clinical Features of SLOS
SLOS presents on a spectrum from mild (detectable only biochemically) to severe. Common features include:
- Intellectual disability (mild to severe)
- Autism-like behavioural features — repetitive behaviours, sensory hypersensitivity, aggression
- Characteristic 2nd-3rd toe syndactyly (fused toes) — a hallmark physical sign
- Genital abnormalities in males (hypospadias, undescended testes)
- Cleft palate and micrognathia
- Feeding difficulties in infancy — poor suck, gastro-oesophageal reflux
- Photosensitivity (7-DHC in the skin reacts abnormally to UV light)
- Growth restriction — SLOS children are often underweight, not overweight
The Dietary Challenge: The Opposite of Conventional Wisdom
Here is the critical principle that differentiates SLOS from every other condition on this website:
In SLOS, dietary cholesterol is therapeutic — not harmful. High-cholesterol foods like eggs, meat and full-fat dairy are beneficial, not restricted.
Because the body cannot synthesise adequate cholesterol endogenously, dietary cholesterol can partially bypass the defective enzyme and raise plasma cholesterol levels. Studies have shown cholesterol supplementation improves:
- Growth (weight gain in underweight children)
- Behaviour (reduced irritability, aggression, self-injury)
- Sleep patterns
- Muscle tone and motor function
What "Cholesterol Supplementation" Means in Practice
Cholesterol supplementation in SLOS can be achieved in two ways:
- Dietary cholesterol: Maximising natural food sources of cholesterol in every meal
- Pharmaceutical cholesterol powder: Pure cholesterol powder (anhydrous cholesterol) mixed into food — available from compounding pharmacies in South Africa (compounding pharmacies in Johannesburg, Cape Town and Durban can prepare this on prescription)
Diet for SLOS in South Africa
High-Cholesterol Foods to Prioritise
The following foods provide the most dietary cholesterol and should be included at every meal for a person with SLOS:
- Eggs: The best single source of dietary cholesterol (approximately 186 mg per large egg yolk). Aim for 2–4 eggs daily. Scrambled, fried in butter, boiled, poached — all count
- Full-fat dairy: Butter, full-cream milk, full-fat yoghurt, hard cheeses (cheddar, gouda), cream. Do not use low-fat versions — these have reduced cholesterol content
- Meat: Red meat (beef, lamb), chicken with skin, pork, offal (liver is especially cholesterol-rich). Biltong is an excellent convenient high-cholesterol, high-protein snack
- Shellfish: Prawns and calamari are among the highest-cholesterol seafood options
- Fish roe (fish eggs): If accessible, extremely cholesterol-dense
- Organ meats: Beef liver, chicken liver (peri-peri chicken livers — a South African favourite) provide exceptional cholesterol density
What to Avoid
- Statins (cholesterol-lowering drugs) — ABSOLUTELY CONTRAINDICATED: Statins work by further blocking cholesterol synthesis. In SLOS, they would worsen the already-deficient cholesterol levels and could be life-threatening. This applies to all statins (atorvastatin, rosuvastatin, simvastatin, etc.). Never allow a prescriber unfamiliar with SLOS to prescribe these.
- Low-fat diets: Counter-productive. Do not follow mainstream "heart-healthy" low-fat dietary advice
- Plant sterols: Found in "cholesterol-lowering" margarines (e.g. Flora ProActiv). Plant sterols compete with and reduce dietary cholesterol absorption — avoid entirely in SLOS
Weight Management Context in SLOS
The weight management challenge in SLOS is almost always the opposite of the typical weight-loss scenario:
- Children with SLOS are typically underweight due to feeding difficulties, dysphagia (swallowing problems), gastro-oesophageal reflux and poor appetite. The goal is often weight gain.
- Severe SLOS may require nasogastric (NG) tube or gastrostomy (PEG) tube feeding. Speech-Language Therapists (SLTs) trained in dysphagia management are essential — available at Red Cross War Memorial Children's Hospital (Cape Town) and Chris Hani Baragwanath Academic Hospital (Johannesburg).
- Adults with mild SLOS and intellectual disability may develop obesity, particularly if mobile independence is limited and dietary education is absent. In this population, caloric management while maintaining cholesterol sufficiency requires careful dietitian guidance.
Photosensitivity and Nutrition
SLOS patients are abnormally sensitive to sunlight because 7-DHC in the skin produces harmful reactive oxygen species when exposed to UV. This is particularly relevant in South Africa's high-UV environment.
- Apply SPF 50+ sunscreen before any outdoor time — Koolasun SPF 50 Kids is a locally produced option
- Wear protective clothing and sun hats — especially important when exercising outdoors
- Antioxidants may provide some protection: vitamin C (guavas, citrus), vitamin E (avocado, sunflower seeds), selenium (Brazil nuts — 2 per day provides the RDA)
Exercise and Physical Activity
Exercise for SLOS patients must be adapted to the individual's degree of intellectual and physical disability:
- For children: Physiotherapy-led movement, hydrotherapy (heated pools), sensory-friendly physical activity. Occupational therapists can design sensory diets that include proprioceptive physical activity to reduce behavioural challenges.
- For adults with mild SLOS: Structured daily walking, swimming, dancing or cycling on a stationary bike. Routine is key — people with intellectual disability respond best to predictable structured schedules.
- Photosensitivity precautions: Exercise indoors or early morning (before 10:00) or late afternoon (after 16:00) in South Africa to minimise UV exposure. Apply sunscreen regardless.
Simvastatin — Emerging Experimental Evidence
Note: A controversial area of SLOS research involves paradoxical use of low-dose simvastatin in some SLOS patients. The rationale is that simvastatin may reduce 7-DHC accumulation by a different mechanism. This is experimental and NOT standard practice. It should only ever be considered under the guidance of a metabolic disease specialist with deep SLOS expertise. Do not attempt this without specialist supervision.
Diagnosing SLOS in South Africa
SLOS is confirmed by:
- Plasma 7-dehydrocholesterol (7-DHC) assay: Elevated 7-DHC is the biochemical hallmark. Available at specialised metabolic laboratories — the Division of Human Genetics at NHLS (National Health Laboratory Service), working with Red Cross or Charlotte Maxeke hospitals, can arrange this.
- DHCR7 gene sequencing: Confirms the mutation. Available through Division of Human Genetics, UCT or Wits. Useful for family genetic counselling.
- Plasma cholesterol: Often low, but may be in the low-normal range in milder cases — do not rely on cholesterol alone for diagnosis.
SA Specialist Resources
- Division of Human Genetics, UCT/Groote Schuur: (021) 406-6295 — metabolic genetics service for Western Cape
- Division of Human Genetics, Wits/Charlotte Maxeke: Gauteng metabolic genetics referrals
- Red Cross War Memorial Children's Hospital: Paediatric metabolic disease team, Cape Town
- Speech-Language Therapy: Essential for dysphagia management — ask for referral at your regional academic hospital
- ADSA dietitians (adsa.org.za): Ask specifically for a dietitian with experience in inborn errors of metabolism
Key Takeaways
- SLOS is a cholesterol deficiency — dietary cholesterol (eggs, butter, meat, full-fat dairy) is therapeutic, not harmful
- Statins and plant sterol margarines are absolutely contraindicated in SLOS
- Children are typically underweight — the priority is adequate nutrition and weight gain, not weight loss
- Adults with mild SLOS may develop obesity — a dietitian experienced in metabolic disease is essential
- Severe photosensitivity in South Africa's climate requires vigilant sun protection
- Always manage SLOS under specialist metabolic and genetic supervision — never attempt dietary changes in severe SLOS without a specialist dietitian
Disclaimer: This article is for informational purposes only and does not constitute medical advice. SLOS is a complex metabolic disorder requiring specialist medical and dietitian supervision. Never alter a SLOS patient's diet or medications without guidance from a metabolic disease specialist. If you suspect SLOS in a child or adult, seek urgent referral to a genetic metabolic service.